@article{MTMT:34575749, title = {Mechanism of Intestinal Epithelial Absorption and Electrophysiological Regulation of the Shrimp Peptide QMDDQ}, url = {https://m2.mtmt.hu/api/publication/34575749}, author = {Li, W. and Li, H. and Song, J. and Xing, Y. and Fang, L. and Wang, X. and Wu, D. and Min, W.}, doi = {10.1021/acs.jafc.3c05714}, journal-iso = {J AGR FOOD CHEM}, journal = {JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, volume = {72}, unique-id = {34575749}, issn = {0021-8561}, abstract = {We investigated the absorption mechanism of the shrimp peptide QMDDQ in small intestines, explored its physiological function in inhibiting neuronal hyperactivity, and verified its entry into the brain in vivo to display functional activity. The everted rat sac model and a Caco-2 paracellular absorption monolayer model were used, indicating that QMDDQ has a good absorption capacity with an apparent permeability coefficient (Papp) > 1 × 10-6 cm/s and the absorption of QMDDQ was concentration-dependent. When the concentration of QMDDQ was 1 mM and the transport time was 180 min, the highest absorption concentration of QMDDQ was 41.17 ± 3.48 μM (P < 0.05). The myosin light-chain kinase (MLCK)-specific inhibitor ML-7 and activator MPA, Western blotting, and immunofluorescence results showed that QMDDQ absorption takes place by mediating the MLCK-p-MLCK-MLC signaling pathway, reversibly opening the zonula occludens-1 (ZO-1), occludin in tight junctions (TJs), upregulating claudin-2 expression, and reaching targets through blood to inhibit neuronal overactivity. Results of fluorescence imaging in vivo verified that QMDDQ could enter the brain 4 h after oral administration. The results provide a theoretical foundation for the mechanism of paracellular absorption of active peptides and a starting point for the development of functional foods for Alzheimer’s disease intervention. © 2023 American Chemical Society.}, keywords = {Brain; Animals; Humans; PEPTIDES; PEPTIDES; IN-VIVO; NEURONS; metabolism; PEPTIDE; RATS; Intestinal Mucosa; intestine mucosa; human; animal; Electrophysiology; Caco-2 Cells; Small intestine; tight junction; Tight Junctions; occludin; occludin; fluorescence imaging; myosin light chain; Physiological functions; myosin light chain kinase; Caco-2 cell line; Myosin Light Chains; rat; paracellular; Neuronal hyperactivity; Neuronal hyperactivity; Mlck; Functional activities; Absorption mechanisms; paracellular absorption; shrimp peptide; Paracellular absorption; Shrimp peptide}, year = {2024}, eissn = {1520-5118}, pages = {326-338} } @article{MTMT:34575750, title = {Human blood lipid profiles after dietary supplementation of different omega 3 ethyl esters formulations}, url = {https://m2.mtmt.hu/api/publication/34575750}, author = {Donnarumma, D. and Di, Salle A. and Micalizzi, G. and Vento, F. and La, Tella R. and Iannotta, P. and Trovato, E. and Melone, M.A.B. and Rigano, F. and Donato, P. and Mondello, L. and Peluso, G.}, doi = {10.1016/j.jchromb.2023.123922}, journal-iso = {J CHROMATOGR B}, journal = {JOURNAL OF CHROMATOGRAPHY B}, volume = {1231}, unique-id = {34575750}, issn = {1570-0232}, abstract = {The validity of omega 3 fatty acids (ω3 FAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as dietary supplements has been widely proved. It's well known in fact, that they protect against cardiovascular diseases, reduce the levels of triacylglycerides (TAGs) and cholesteryl esters (CEs) in blood, and have anti-inflammatory activity. For these reasons, in the last few years the production of dietary supplement containing ω3 has increased significantly. In this context, the possibility to obtain ω3 and other high value molecules from alternative sources as fish waste, in accordance with the principles of circular economy, becomes an enormous attractive. In addition, the opportunity of creating new products, with greater health benefits, represents an interesting challenge. The current study was focused on the extraction of ω3 fatty acids and peptides from tuna waste industry, to realize a new dietary supplement. To this purpose, a supercritical fluid extraction (SFE) method was developed to separate, isolate, and enrich the different fractions subsequently used to produce an innovative formulate. The obtained supplement was characterized in terms of fatty acids esterified ester (FAEE) composition by gas chromatography (GC) coupled to both flame ionization detection (FID) and mass spectrometry (MS), and content of heavy metals by inductively coupled plasma–mass spectrometry (ICP-MS). The effects of ω3 supplementation on metabolism and circulating lipid profiles was tested on 12 volunteers and assessed by GC-FID analysis of whole blood collected on paper support (Dried Blood Spot, DBS) at the beginning of the study and after thirty days. The results of plasma fatty acids levels after 30 days showed a significant decrease in the ω6/ω3 ratio, as well as the saturated/polyunsaturated fatty acids (SFA/PUFA) ratio, compared to subjects who took the ω3 ethyl esters unformulated. The novel formulated supplements proved to be extremely interesting and promising products, due to a significant increase in bioavailability, that makes it highly competitive in the current panorama of the nutraceutical industry. © 2023 The Authors}, keywords = {Animals; Adult; Female; Middle Aged; Male; Humans; EXTRACTION; BLOOD; ARTICLE; LIPIDS; ESTERS; ESTERS; human; animal; controlled study; fish; randomized controlled trial; normal human; human experiment; diet supplementation; Heavy metals; Mass spectrometry; Mass spectrometry; lipid metabolism; Dietary Supplements; Dietary Supplements; NUTRITION; fatty acids; fatty acids; drug formulation; unclassified drug; double blind procedure; fatty acid; lipid composition; blood analysis; saturated fatty acid; ESTER; Gas chromatography; Gas chromatography; SUPERCRITICAL FLUIDS; BIOCHEMISTRY; Fatty Acids, Omega-3; Vitamins; fish oil; mass fragmentography; drug isolation; inductively coupled plasma mass spectrometry; Transesterification; Gas Chromatography-Mass Spectrometry; LIPIDOMICS; LIPIDOMICS; LIPIDOMICS; Lipid profile; Eicosapentaenoic Acid; icosapentaenoic acid; omega 3 fatty acid; omega 3 fatty acid; Oils and fats; Ionization of gases; effluent treatment; omega 6 fatty acid; Chemical contamination; Dried blood spot; Dried blood spot; Dietary supplement; dried blood spot testing; Food waste; Ethyl esters; Fatty acid ethyl esters; Waste valorization; flame ionization detection; lipid fingerprinting; Blue Economy; Tuna; 'current; Waste valorizations; Tuna fish industry; Blue economies; Fatty acid ethyl ester; Tuna fish industry; Tuna fishes; omega 3 ethyl ester f; omega 3 ethyl esters nf}, year = {2023}, eissn = {1873-376X} } @article{MTMT:33550880, title = {Peptide permeation enhancers for improving oral bioavailability of macromolecules}, url = {https://m2.mtmt.hu/api/publication/33550880}, author = {Kim, D. and Jin, L. and Park, E.J. and Na, D.H.}, doi = {10.1007/s40005-022-00609-4}, journal-iso = {J PHARM INVEST}, journal = {JOURNAL OF PHARMACEUTICAL INVESTIGATION}, volume = {53}, unique-id = {33550880}, issn = {2093-5552}, abstract = {Background: Oral delivery of macromolecules has been limited mainly by their low intestinal permeability. Chemical permeation enhancers (CPEs) are typically used to improve intestinal permeation. However, their targets are unspecified and absorption enhancing mechanisms are not fully proven. In addition, they show undesired toxicity. Peptide permeation enhancers (PPEs) have been gaining continuous interest as they modulate specific types of tight-junction proteins with high efficacy compared to that achieved by CPEs. Moreover, their reversible action on increasing the intestinal permeability demonstrably indicates their potential as a safe ingredient. Area covered: This review presents an overview of PPEs that have demonstrated sufficient safety and efficacy in increasing the intestinal absorption of synthetic peptides or biologics. Their basic concepts are briefly provided, and the distinct characteristics of each PPE are discussed with a particular focus on their absorption enhancement activity and the rationale for this improvement. Expert opinion: PPE is a highly promising active excipient for the oral formulations of macromolecules that can replace target-unspecified CPEs. The use of PPEs in oral formulations will rapidly increase as their in vivo safety and stability issues are being overcome. This review provides a guide to select the optimal PPEs for the oral formulations of macromolecules and can further be used to identify novel PPEs with the desired attributes for this purpose. © 2022, The Author(s) under exclusive licence to The Korean Society of Pharmaceutical Sciences and Technology.}, keywords = {PEPTIDES; PROTEINS; BIOAVAILABILITY; ORAL DELIVERY; Permeation enhancer}, year = {2023}, eissn = {2093-6214}, pages = {59-72} } @article{MTMT:34136759, title = {Applications of Functional Polymer Modified Nanoparticles in the Oral Drug Delivery System [功能性材料修饰的纳米粒在口服给药系统中的应用]}, url = {https://m2.mtmt.hu/api/publication/34136759}, author = {Liu, Wan and Yang, Shilin and Jin, Yi and Feng, Jianfang and Tu, Liangxing}, doi = {10.16522/j.cnki.cjph.2023.01.005}, journal-iso = {Chinese Journal of Pharmaceuticals}, journal = {Chinese Journal of Pharmaceuticals}, volume = {54}, unique-id = {34136759}, issn = {1001-8255}, year = {2023}, pages = {48-56} } @article{MTMT:34036946, title = {Storming the gate. New approaches for targeting the dynamic tight junction for improved drug delivery}, url = {https://m2.mtmt.hu/api/publication/34036946}, author = {Ramirez-Velez, Isabela and Belardi, Brian}, doi = {10.1016/j.addr.2023.114905}, journal-iso = {ADV DRUG DELIV REV}, journal = {ADVANCED DRUG DELIVERY REVIEWS}, volume = {199}, unique-id = {34036946}, issn = {0169-409X}, year = {2023}, eissn = {1872-8294}, orcid-numbers = {Belardi, Brian/0000-0003-3608-0164} } @article{MTMT:33547706, title = {Soluplus® promotes efficient transport of meloxicam to the central nervous system via nasal administration}, url = {https://m2.mtmt.hu/api/publication/33547706}, author = {Sipos, Bence and Bella, Zsolt and Gróf, Ilona and Veszelka, Szilvia and Deli, Mária Anna and Szűcs, Kálmán Ferenc and Sztojkov-Ivanov, Anita and Ducza, Eszter and Gáspár, Róbert and Kecskeméti, Gábor and Janáky, Tamás and Volk, Balázs and Budai-Szűcs, Mária and Ambrus, Rita and Révész, Piroska and Pannonhalminé Csóka, Ildikó and Katona, Gábor}, doi = {10.1016/j.ijpharm.2023.122594}, journal-iso = {INT J PHARM}, journal = {INTERNATIONAL JOURNAL OF PHARMACEUTICS}, volume = {632}, unique-id = {33547706}, issn = {0378-5173}, year = {2023}, eissn = {1873-3476}, orcid-numbers = {Sipos, Bence/0000-0002-0131-4728; Deli, Mária Anna/0000-0001-6084-6524; Gáspár, Róbert/0000-0002-1571-7579; Kecskeméti, Gábor/0000-0002-5584-6869; Janáky, Tamás/0000-0002-6466-8283; Volk, Balázs/0000-0002-2019-1874; Budai-Szűcs, Mária/0000-0001-5187-5702; Révész, Piroska/0000-0002-5336-6052; Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781; Katona, Gábor/0000-0003-1564-4813} } @mastersthesis{MTMT:34067465, title = {The battle against antimicrobial resistant bacterial infections. Next stage development of antimicrobial peptides}, url = {https://m2.mtmt.hu/api/publication/34067465}, isbn = {9789464197822}, author = {van Gent, ME}, unique-id = {34067465}, year = {2023} } @article{MTMT:34575752, title = {Nanocarriers transport across the gastrointestinal barriers. The contribution to oral bioavailability via blood circulation and lymphatic pathway}, url = {https://m2.mtmt.hu/api/publication/34575752}, author = {Wang, D. and Jiang, Q. and Dong, Z. and Meng, T. and Hu, F. and Wang, J. and Yuan, H.}, doi = {10.1016/j.addr.2023.115130}, journal-iso = {ADV DRUG DELIV REV}, journal = {ADVANCED DRUG DELIVERY REVIEWS}, volume = {203}, unique-id = {34575752}, issn = {0169-409X}, abstract = {Oral administration is the preferred route of drug delivery in clinical practice due to its noninvasiveness, safety, convenience, and high patient compliance. The gastrointestinal tract (GIT) plays a crucial role in facilitating the targeted delivery of oral drugs. However, the GIT presents multiple barriers that impede drug absorption, including the gastric barrier in the stomach and the mucus and epithelial barriers in the intestine. In recent decades, nanotechnology has emerged as a promising approach for overcoming these challenges by utilizing nanocarrier-based drug delivery systems such as liposomes, micelles, polymeric nanoparticles, solid lipid nanoparticles, and inorganic nanoparticles. Encapsulating drugs within nanocarriers not only protects them from degradation but also enhances their transport and absorption across the GIT, ultimately improving oral bioavailability. The aim of this review is to elucidate the mechanisms underlying nanocarrier-mediated transportation across the GIT into systemic circulation via both the blood circulation and lymphatic pathway. © 2023 Elsevier B.V.}, keywords = {Humans; metabolism; PHAGOCYTOSIS; BLOOD; ENDOCYTOSIS; signal transduction; review; human; nonhuman; epithelium cell; oral drug administration; Administration, Oral; NANOPARTICLES; NANOPARTICLES; gastrointestinal; drug delivery system; drug delivery system; gastrointestinal tract; gastrointestinal tract; gastrointestinal tract; gastrointestinal tract; lymphatic system; Drug Delivery Systems; hydrophilicity; physical chemistry; drug carrier; Micelles; nanoparticle; Liposomes; Drug Carriers; lectin; BIOAVAILABILITY; BIOAVAILABILITY; BIOAVAILABILITY; BIOCHEMISTRY; Application; goblet cell; blood flow; Biological Availability; Nanotechnology; Nanotechnology; tight junction; Blood Circulation; cyanocobalamin; Pinocytosis; Oral drug delivery; Oral drug delivery; mucoadhesion; gastrointestinal tract function; Transport mechanism; Transport mechanism; arginylglycylaspartic acid; nanocarrier; Oral administration; Targeted drug delivery; Controlled drug delivery; Nanocarriers; Oral bioavailabilities; gastrointestinal barrier; gastrointestinal barrier; Lipid nanoparticle; invasin; stomach mucus; intestinal availability}, year = {2023}, eissn = {1872-8294} } @article{MTMT:34136758, title = {Advances in non-invasive drug delivery across the blood-brain barrier [非侵入性透血脑屏障药物递送研究进展]}, url = {https://m2.mtmt.hu/api/publication/34136758}, author = {You, Lili and Fu, Wenliang and Zhang, Chao and Xu, Donggang}, doi = {10.7644/j.issn.1674-9960.2023.01.013}, journal-iso = {Military Medical Sciences}, journal = {Military Medical Sciences}, volume = {47}, unique-id = {34136758}, issn = {1674-9960}, year = {2023}, pages = {75-80} } @mastersthesis{MTMT:33580448, title = {Unravelling the modulation of tight junctions: Molecular mechanisms and permeation enhancement}, url = {https://m2.mtmt.hu/api/publication/33580448}, author = {Brunner, J}, doi = {10.13097/archive-ouverte/unige:161111}, unique-id = {33580448}, year = {2022} } @article{MTMT:33407453, title = {Screening for effective cell-penetrating peptides with minimal impact on epithelial cells and gut commensals in vitro}, url = {https://m2.mtmt.hu/api/publication/33407453}, author = {Gelli, Hitesh P. and Vazquez-Uribe, Ruben and Sommer, Morten Otto Alexander}, doi = {10.3389/fphar.2022.1049324}, journal-iso = {FRONT PHARMACOL}, journal = {FRONTIERS IN PHARMACOLOGY}, volume = {13}, unique-id = {33407453}, abstract = {One of the biggest challenges for oral drug absorption is the epithelial barrier of the gastrointestinal tract. The use of cell-penetrating peptides (CPPs) to modulate the epithelial barrier function is known to be an effective strategy to improve drug absorption and bioavailability. In this study we compare side-by-side, 9 most promising CPPs to study their cytotoxicity (Cytotox Red dye staining) and cell viability (AlamarBlue staining) on epithelial cells and their effects on paracellular permeability of the intestinal barrier in vitro in a differentiated Caco-2 epithelial monolayer model. The data revealed that 4 out of 9 well-studied CPPs significantly improved Caco-2 paracellular permeability without compromising on cellular health. To assess the impact of CPPs on the human microbiota we studied the antimicrobial effects of the 4 effective CPPs from our permeation studies against 10 representative strains of the gut microbiota in vitro using microbroth dilution. Our data revealed that these 4 CPPs affected the growth of almost all tested commensal strains. Interestingly, we found that two synthetic CPPs (Shuffle and Penetramax) outperformed all the other CPPs in their ability to increase intestinal paracellular permeability at 50 mu M and had only a small to moderate effect on the tested gut commensal strains. Based on these data Shuffle and Penetramax represent relevant CPPs to be further characterized in vivo for safe delivery of poorly absorbed therapeutics while minimizing negative impacts on the gut microbiota.}, keywords = {CYTOTOXICITY; In Vitro; Caco-2 Cells; Cell viability; Intestinal Absorption; gut microbiota; Cell-penetrating peptides; Permeation enhancer}, year = {2022}, eissn = {1663-9812}, orcid-numbers = {Vazquez-Uribe, Ruben/0000-0002-9800-0409; Sommer, Morten Otto Alexander/0000-0003-4005-5674} } @article{MTMT:33550877, title = {Gastrointestinal Permeation Enhancers for the Development of Oral Peptide Pharmaceuticals}, url = {https://m2.mtmt.hu/api/publication/33550877}, author = {Kim, J.C. and Park, E.J. and Na, D.H.}, doi = {10.3390/ph15121585}, journal-iso = {PHARMACEUTICALS-BASE}, journal = {PHARMACEUTICALS}, volume = {15}, unique-id = {33550877}, abstract = {Recently, two oral-administered peptide pharmaceuticals, semaglutide and octreotide, have been developed and are considered as a breakthrough in peptide and protein drug delivery system development. In 2019, the Food and Drug Administration (FDA) approved an oral dosage form of semaglutide developed by Novo Nordisk (Rybelsus®) for the treatment of type 2 diabetes. Subsequently, the octreotide capsule (Mycapssa®), developed through Chiasma’s Transient Permeation Enhancer (TPE) technology, also received FDA approval in 2020 for the treatment of acromegaly. These two oral peptide products have been a significant success; however, a major obstacle to their oral delivery remains the poor permeability of peptides through the intestinal epithelium. Therefore, gastrointestinal permeation enhancers are of great relevance for the development of subsequent oral peptide products. Sodium salcaprozate (SNAC) and sodium caprylate (C8) have been used as gastrointestinal permeation enhancers for semaglutide and octreotide, respectively. Herein, we briefly review two approved products, Rybelsus® and Mycapssa®, and discuss the permeation properties of SNAC and medium chain fatty acids, sodium caprate (C10) and C8, focusing on Eligen technology using SNAC, TPE technology using C8, and gastrointestinal permeation enhancement technology (GIPET) using C10. © 2022 by the authors.}, keywords = {PEPTIDES; ORAL DELIVERY; Medium chain fatty acids; permeation enhancers; sodium salcaprozate}, year = {2022}, eissn = {1424-8247} } @article{MTMT:33351318, title = {Systemic and brain delivery of antidiabetic peptides through nasal administration using cell-penetrating peptides}, url = {https://m2.mtmt.hu/api/publication/33351318}, author = {Maeng, Jeehye and Lee, Kyunglim}, doi = {10.3389/fphar.2022.1068495}, journal-iso = {FRONT PHARMACOL}, journal = {FRONTIERS IN PHARMACOLOGY}, volume = {13}, unique-id = {33351318}, abstract = {The intranasal route has emerged as a promising strategy that can direct delivery of drugs into the systemic circulation because the high-vascularized nasal cavity, among other advantages, avoids the hepatic first-pass metabolism. The nose-to-brain pathway provides a non-invasive alternative to other routes for the delivery of macromolecular therapeutics. A great variety of methodologies has been developed to enhance the efficiency of transepithelial translocation of macromolecules. Among these, the use of cell-penetrating peptides (CPPs), short protein transduction domains (PTDs) that facilitate the intracellular transport of various bioactive molecules, has become an area of extensive research in the intranasal delivery of peptides and proteins either to systemic or to brain compartments. Some CPPs have been applied for the delivery of peptide antidiabetics, including insulin and exendin-4, for treating diabetes and Alzheimer’s disease. This review highlights the current status of CPP-driven intranasal delivery of peptide drugs and its potential applicability as a universal vehicle in the nasal drug delivery.}, year = {2022}, eissn = {1663-9812} } @article{MTMT:32597774, title = {Cell-Penetrating Peptides as Carriers for Transepithelial Drug Delivery}, url = {https://m2.mtmt.hu/api/publication/32597774}, author = {Panou, D.A. and Diedrichsen, R.G. and Kristensen, M. and Nielsen, H.M.}, doi = {10.1007/978-1-0716-1752-6_24}, journal-iso = {METHODS MOL BIOL}, journal = {METHODS IN MOLECULAR BIOLOGY}, volume = {2383}, unique-id = {32597774}, issn = {1064-3745}, abstract = {This chapter describes the use of cell-penetrating peptides (CPPs) as carriers for transepithelial delivery of therapeutic peptides. Assessment of transepithelial peptide permeation and the mechanisms of action that permeability enhancing drug carriers exert on the epithelium requires subtle sample preparation and analysis by orthogonal methods. Here, the preparation and use of CPP-insulin physical mixture samples including the quantification of insulin by enzyme-linked immunosorbent assay (ELISA) is described. In addition, effects of CPPs on the epithelium and its barrier properties immediately upon exposure and after a recovery period are evaluated by epithelial cell viability, transepithelial electrical resistance, immunostaining of the tight junction associated zonula occludens (ZO-1) protein, and actin cytoskeleton staining. © 2022, The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.}, keywords = {immunohistochemistry; human; INSULIN; INSULIN; enzyme linked immunosorbent assay; epithelium cell; DISSOLUTION; Cell Membrane Permeability; human cell; drug delivery system; drug carrier; sample preparation; actin cytoskeleton; Cell viability; human cell culture; actin filament; tight junction; tight junction; Oral drug delivery; Caco-2; cell penetrating peptide; recombinant human insulin; Caco-2 cell line; transepithelial resistance; balanced salt solution; Epithelial cell viability; Epithelial recovery; Peptide permeation}, year = {2022}, eissn = {1940-6029}, pages = {371-384} } @article{MTMT:32598589, title = {Biotherapeutic effect of cell-penetrating peptides against microbial agents: a review}, url = {https://m2.mtmt.hu/api/publication/32598589}, author = {Sadiq, I.Z. and Muhammad, A. and Mada, S.B. and Ibrahim, B. and Umar, U.A.}, doi = {10.1080/21688370.2021.1995285}, journal-iso = {TISS BARR}, journal = {TISSUE BARRIERS}, volume = {10}, unique-id = {32598589}, issn = {2168-8362}, abstract = {Selective permeability of biological membranes represents a significant barrier to the delivery of therapeutic substances into both microorganisms and mammalian cells, restricting the access of drugs into intracellular pathogens. Cell-penetrating peptides usually 5–30 amino acids with the characteristic ability to penetrate biological membranes have emerged as promising antimicrobial agents for treating infections as well as an effective delivery modality for biological conjugates such as nucleic acids, drugs, vaccines, nanoparticles, and therapeutic antibodies. However, several factors such as antimicrobial resistance and poor drug delivery of the existing medications justify the urgent need for developing a new class of antimicrobials. Herein, we review cell-penetrating peptides (CPPs) used to treat microbial infections. Although these peptides are biologically active for infections, effective transduction into membranes and cargo transport, serum stability, and half-life must be improved for optimum functions and development of next-generation antimicrobial agents. © 2021 Taylor & Francis Group, LLC.}, keywords = {Antimicrobial; Biotherapeutics; Mechanisms of action; Cell-penetrating peptides; Delivery vectors}, year = {2022}, eissn = {2168-8370} } @article{MTMT:31642822, title = {Transport Studies Using Blood-Brain Barrier In Vitro Models. A Critical Review and Guidelines}, url = {https://m2.mtmt.hu/api/publication/31642822}, author = {Santa Maria, Anaraquel and Heymans, Marjolein and Walter, Fruzsina and Culot, Maxime and Gosselet, Fabien and Deli, Mária Anna and Neuhaus, Winfried}, doi = {10.1007/164_2020_394}, journal-iso = {HANDB EXP PHARMACOL}, journal = {HANDBOOK OF EXPERIMENTAL PHARMACOLOGY}, volume = {273}, unique-id = {31642822}, issn = {0171-2004}, abstract = {Permeation is one of the most evaluated parameters using preclinical in vitro blood-brain barrier models, as it has long been considered to be one of the major factors influencing central nervous system drug delivery. Blood-brain barrier permeability can be defined as the speed at which a compound crosses the brain endothelial cell barrier and is employed to assess barrier tightness, which is a crucial feature of brain capillaries in vivo. In addition, it is used to assess brain drug penetration. We review traditionally used methods to assess blood-brain barrier permeability in vitro and summarize often neglected in vivo (e.g., plasma protein and brain tissue binding) or in vitro (e.g., culture insert materials or methodology) factors that influence this property. These factors are crucial to consider when performing BBB permeability assessments, and especially when comparing permeability data obtained from different models, since model diversification significantly complicates inter-study comparisons. Finally, measuring transendothelial electrical resistance can be used to describe blood-brain barrier tightness; however, several parameters should be considered while comparing these measurements to the blood-brain barrier permeability to paracellular markers.}, keywords = {drug transport; penetration; brain capillary endothelial cells; TEER; Paracellular transport; Cell layer tightness}, year = {2022}, pages = {187-204}, orcid-numbers = {Santa Maria, Anaraquel/0000-0003-3505-5477; Walter, Fruzsina/0000-0001-8145-2823; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:33091723, title = {A Second Life for MAP, a Model Amphipathic Peptide}, url = {https://m2.mtmt.hu/api/publication/33091723}, author = {Silva, S. and Kurrikoff, K. and Langel, Ü. and Almeida, A.J. and Vale, N.}, doi = {10.3390/ijms23158322}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {33091723}, issn = {1661-6596}, abstract = {Cell-penetrating peptides (CPP) have been shown to be efficient in the transport of cargoes into the cells, namely siRNA and DNA, proteins and peptides, and in some cases, small therapeutics. These peptides have emerged as a solution to increase drug concentrations in different tissues and various cell types, therefore having a relevant therapeutic relevance which led to clinical trials. One of them, MAP, is a model amphipathic peptide with an α-helical conformation and both hydrophilic and hydrophobic residues in opposite sides of the helix. It is composed of a mixture of alanines, leucines, and lysines (KLALKLALKALKAALKLA). The CPP MAP has the ability to translocate oligonucleotides, peptides and small proteins. However, taking advantage of its unique properties, in recent years innovative concepts were developed, such as in silico studies of modelling with receptors, coupling and repurposing drugs in the central nervous system and oncology, or involving the construction of dual-drug delivery systems using nanoparticles. In addition to designs of MAP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy, this review will be focused on unique molecular structure and how it determines its cellular activity, and also intends to address the most recent and frankly motivating issues for the future. © 2022 by the authors.}, keywords = {metabolism; GENETICS; CNS; Chemistry; NANOPARTICLES; Chemical Phenomena; drug delivery system; Drug Delivery Systems; OLIGONUCLEOTIDE; Oncology; RNA, Small Interfering; SMALL INTERFERING RNA; Hydrophobic and Hydrophilic Interactions; Oligonucleotides; cell penetrating peptide; DELIVERY SYSTEM; Cell-penetrating peptides; Cell-penetrating peptides; drug repurposing; model amphipathic peptide}, year = {2022}, eissn = {1422-0067} } @article{MTMT:32575627, title = {A Triple Combination of Targeting Ligands Increases the Penetration of Nanoparticles across a Blood-Brain Barrier Culture Model}, url = {https://m2.mtmt.hu/api/publication/32575627}, author = {Veszelka, Szilvia and Mészáros, Mária and Porkoláb, Gergő and Szecskó, Anikó and Kondor, Nóra and Ferenc, Györgyi and Polgár, Tamás Ferenc and Katona, Gábor and Kóta, Zoltán and Kelemen, Lóránd and Páli, Tibor and Vigh, Judit Piroska and Walter, Fruzsina and Bolognin, Silvia and Schwamborn, Jens C. and Jan, Jeng-Shiung and Deli, Mária Anna}, doi = {10.3390/pharmaceutics14010086}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {14}, unique-id = {32575627}, issn = {1999-4923}, year = {2022}, eissn = {1999-4923}, orcid-numbers = {Ferenc, Györgyi/0000-0002-3456-319X; Katona, Gábor/0000-0003-1564-4813; Kóta, Zoltán/0000-0003-2420-8773; Kelemen, Lóránd/0000-0001-7772-2165; Páli, Tibor/0000-0003-1649-1097; Walter, Fruzsina/0000-0001-8145-2823; Bolognin, Silvia/0000-0002-1399-2999; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:33181647, title = {How Nanoparticles Open the Paracellular Route of Biological Barriers: Mechanisms, Applications, and Prospects}, url = {https://m2.mtmt.hu/api/publication/33181647}, author = {Wu, Junrong and Zhu, Zhenjun and Liu, Wenjing and Zhang, Yanli and Kang, Yiyuan and Liu, Jia and Hu, Chen and Wang, Ruolan and Zhang, Manjin and Chen, Lili and Shao, Longquan}, doi = {10.1021/acsnano.2c05317}, journal-iso = {ACS NANO}, journal = {ACS NANO}, volume = {16}, unique-id = {33181647}, issn = {1936-0851}, abstract = {Biological barriers are essential physiological protective systems and obstacles to drug delivery. Nanoparticles (NPs) can access the paracellular route of biological barriers, either causing adverse health impacts on humans or producing therapeutic opportunities. This Review introduces the structural and functional influences of NPs on the key components that govern the paracellular route, mainly tight junctions, adherens junctions, and cytoskeletons. Furthermore, we evaluate their interaction mechanisms and address the influencing factors that determine the ability of NPs to open the paracellular route, which provides a better knowledge of how NPs can open the paracellular route in a safer and more controllable way. Finally, we summarize limitations in the research models and methodologies of the existing research in the field and provide future research direction. This Review demonstrates the in-depth causes for the reversible opening or destruction of the integrity of barriers generated by NPs; more importantly, it contributes insights into the design of NP-based medications to boost paracellular drug delivery efficiency.}, keywords = {Drug delivery; CYTOSKELETON; tight junction; adherens junction; Nanomedicine; Biological barrier; paracellular transportation; reversible opening}, year = {2022}, eissn = {1936-086X}, pages = {15627-15652} } @article{MTMT:32721216, title = {Multifunctional building elements for the construction of peptide drug conjugates}, url = {https://m2.mtmt.hu/api/publication/32721216}, author = {Xu, Liu and Xu, Shan and Xiang, Tangyong and Liu, Heng and Chen, Linwei and Jiang, Baoping and Yao, Junhong and Zhu, Hongliu and Hu, Rongfeng and Chen, Zhipeng}, doi = {10.1016/j.engreg.2022.02.004}, journal-iso = {Engineered Regeneration}, journal = {Engineered Regeneration}, volume = {3}, unique-id = {32721216}, issn = {2666-1381}, year = {2022}, pages = {92-109} } @article{MTMT:32531953, title = {In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin}, url = {https://m2.mtmt.hu/api/publication/32531953}, author = {Akel, Hussein and Pannonhalminé Csóka, Ildikó and Ambrus, Rita and Bocsik, Alexandra and Gróf, Ilona and Mészáros, Mária and Szecskó, Anikó and Kozma, Gábor and Veszelka, Szilvia and Deli, Mária Anna and Kónya, Zoltán and Katona, Gábor}, doi = {10.3390/ijms222413258}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {22}, unique-id = {32531953}, issn = {1661-6596}, year = {2021}, eissn = {1422-0067}, orcid-numbers = {Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781; Kozma, Gábor/0000-0003-2033-0720; Deli, Mária Anna/0000-0001-6084-6524; Kónya, Zoltán/0000-0002-9406-8596; Katona, Gábor/0000-0003-1564-4813} } @article{MTMT:31979449, title = {Target specific tight junction modulators}, url = {https://m2.mtmt.hu/api/publication/31979449}, author = {Brunner, J. and Ragupathy, S. and Borchard, G.}, doi = {10.1016/j.addr.2021.02.008}, journal-iso = {ADV DRUG DELIV REV}, journal = {ADVANCED DRUG DELIVERY REVIEWS}, volume = {171}, unique-id = {31979449}, issn = {0169-409X}, abstract = {Intercellular tight junctions represent a formidable barrier against paracellular drug absorption at epithelia (e.g., nasal, intestinal) and the endothelium (e.g., blood–brain barrier). In order to enhance paracellular transport of drugs and increase their bioavailability and organ deposition, active excipients modulating tight junctions have been applied. First-generation of permeation enhancers (PEs) acted by unspecific interactions, while recently developed PEs address specific physiological mechanisms. Such target specific tight junction modulators (TJMs) have the advantage of a defined specific mechanism of action. To date, merely a few of these novel active excipients has entered into clinical trials, as their lack in safety and efficiency in vivo often impedes their commercialisation. A stronger focus on the development of such active excipients would result in an economic and therapeutic improvement of current and future drugs. © 2021 The Author(s)}, keywords = {BIOCHEMISTRY; drug absorption; Mechanism of action; Tight Junctions; Claudin; occludin; Commercialisation; physiological mechanisms; Zonula occludens; permeation enhancers; Paracellular transport; epithelial permeability; Paracellular pathway; Safety and efficiencies; Intercellular tight junctions}, year = {2021}, eissn = {1872-8294}, pages = {266-288} } @article{MTMT:31845960, title = {Enhancing Intestinal Absorption of a Model Macromolecule via the Paracellular Pathway using E-Cadherin Peptides}, url = {https://m2.mtmt.hu/api/publication/31845960}, author = {Dening, T.J. and Siahaan, T.J. and Hageman, M.J.}, doi = {10.1016/j.xphs.2020.12.018}, journal-iso = {J PHARM SCI}, journal = {JOURNAL OF PHARMACEUTICAL SCIENCES}, volume = {110}, unique-id = {31845960}, issn = {0022-3549}, abstract = {Membrane permeation enhancers have received significant attention in recent years for enabling the oral absorption of poorly permeable drug molecules. In this study, we investigated the ability of His-Ala-Val (HAV) and Ala-Asp-Thr (ADT) peptides derived from the extracellular-1 (EC1) domain of E-cadherin proteins to increase the paracellular permeation and intestinal bioavailability of the poorly permeable model macromolecule, fluorescein-isothiocyanate dextran with average molecular weight 4000 (FD4). The in vitro enzymatic stability of linear and cyclic E-cadherin peptides was characterized under simulated gastric and intestinal conditions, and the cyclic E-cadherin peptides, HAVN1 and ADTC5, which demonstrated excellent stability in vitro, were advanced to in vivo intestinal instillation studies and compared against the established surfactant membrane permeation enhancer, sodium caprate (C10). Cyclic HAVN1 and ADTC5 peptides increased FD4 bioavailability by 7.2- and 4.4-fold compared to control, respectively (not statistically significant). In contrast, C10 provided a statistically significant 10.7-fold relative bioavailability enhancement for FD4. Importantly, this study represents the first report of cyclic E-cadherin peptides as intestinal membrane permeation enhancers. The findings described herein demonstrate the potential of enzymatically stabilized cyclic E-cadherin peptides for increasing poorly permeable drug absorption via the oral route. © 2020 American Pharmacists Association®}, keywords = {ABSORPTION; gastrointestinal; BIOAVAILABILITY; Intestinal Absorption; Oral drug delivery; Paracellular transport; epithelial permeability; absorption enhancer(s); permeation enhancer(s); macromolecular drug delivery}, year = {2021}, eissn = {1520-6017}, pages = {2139-2148} } @article{MTMT:32166213, title = {Revealing the importance of carrier-cargo association in delivery of insulin and lipidated insulin}, url = {https://m2.mtmt.hu/api/publication/32166213}, author = {Diedrichsen, R.G. and Harloff-Helleberg, S. and Werner, U. and Besenius, M. and Leberer, E. and Kristensen, M. and Nielsen, H.M.}, doi = {10.1016/j.jconrel.2021.07.030}, journal-iso = {J CONTROL RELEASE}, journal = {JOURNAL OF CONTROLLED RELEASE}, volume = {338}, unique-id = {32166213}, issn = {0168-3659}, abstract = {Delivery of therapeutic peptides upon oral administration is highly desired and investigations report that the cell-penetrating peptide (CPP) penetratin and its analogues shuffle and penetramax show potential as carriers to enhance insulin delivery. Exploring this, the specific aim of the present study was to understand the impact that their complexation with a lipidated or non-lipidated therapeutic cargo would have on the delivery, to evaluate the effect of differences in membrane interactions in vitro and in vivo, as well as to deduce the mode of action leading to enhanced delivery. Fundamental biophysical aspects were studied by a range of orthogonal methods. Transepithelial permeation of therapeutic peptide was evaluated using the Caco-2 cell culture model supplemented with epithelial integrity measurements, real-time assessment of the carrier peptide effects on cell viability and on mode of action. Pharmacokinetic and pharmacodynamic (PK/PD) parameters were evaluated following intestinal administration to rats and tissue effects were investigated by histology. The biophysical studies revealed complexation of insulin with shuffle and penetramax, but not with penetratin. This corresponded to enhanced transepithelial permeation of insulin, but not of lipidated insulin, when in physical mixture with shuffle or penetramax. The addition of shuffle and penetramax was associated with a lowering of Caco-2 cell monolayer integrity and viability, where the lowering of cell viability was immediate, but reversible. Insulin delivery in rats was enhanced by shuffle and penetramax and accompanied by a 10–20-fold decrease in blood glucose with immediate effect on the intestinal mucosa. In conclusion, shuffle and penetramax, but not penetratin, demonstrated to be potential candidates as carriers for transmucosal delivery of insulin upon oral administration, and their effect depended on association with both cargo and cell membrane. Interestingly, the present study provides novel mechanistic insight that peptide carrier-induced cargo permeation points towards enhancement via the paracellular route in the tight epithelium. This is different from the anticipated belief being that it is the cell-penetrating capability that facilitate transepithelial cargo permeation via a transcellular route. © 2021 The Authors}, keywords = {PEPTIDES; CELLS; MECHANISM; MECHANISMS; PERMEATION; RATS; INSULIN; INSULIN; Histology; Histology; cell culture; PENETRATIN; Insulin delivery; Mode of action; Oral administration; MEMBRANE INTERACTIONS; Membrane interaction; therapeutic peptides; intestinal delivery; intestinal delivery; Carrier peptide; Carrier peptide; Lipidated cargo; Lipidated cargo; Penetramax; Penetramax}, year = {2021}, eissn = {1873-4995}, pages = {8-21} } @article{MTMT:31995751, title = {Development of In Situ Gelling Meloxicam-Human Serum Albumin Nanoparticle Formulation for Nose-to-Brain Application}, url = {https://m2.mtmt.hu/api/publication/31995751}, author = {Katona, Gábor and Sipos, Bence and Budai-Szűcs, Mária and Balogh, György Tibor and Veszelka, Szilvia and Gróf, Ilona and Deli, Mária Anna and Volk, Balázs and Révész, Piroska and Pannonhalminé Csóka, Ildikó}, doi = {10.3390/pharmaceutics13050646}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {13}, unique-id = {31995751}, issn = {1999-4923}, abstract = {The aim of this study was to develop an intranasal in situ thermo-gelling meloxicam-human serum albumin (MEL-HSA) nanoparticulate formulation applying poloxamer 407 (P407), which can be administered in liquid state into the nostril, and to increase the resistance of the formulation against mucociliary clearance by sol-gel transition on the nasal mucosa, as well as to improve drug absorption. Nanoparticle characterization showed that formulations containing 12-15% w/w P407 met the requirements of intranasal administration. The Z-average (in the range of 180-304 nm), the narrow polydispersity index (PdI, from 0.193 to 0.328), the zeta potential (between -9.4 and -7.0 mV) and the hypotonic osmolality (200-278 mOsmol/L) of MEL-HSA nanoparticles predict enhanced drug absorption through the nasal mucosa. Based on the rheological, muco-adhesion, drug release and permeability studies, the 14% w/w P407 containing formulation (MEL-HSA-P14%) was considered as the optimized formulation, which allows enhanced permeability of MEL through blood-brain barrier-specific lipid fraction. Cell line studies showed no cell damage after 1-h treatment with MEL-HSA-P14% on RPMI 2650 human endothelial cells' moreover, enhanced permeation (four-fold) of MEL from MEL-HSA-P14% was observed in comparison to pure MEL. Overall, MEL-HSA-P14% can be promising for overcoming the challenges of nasal drug delivery.}, keywords = {Quality by Design; rapid equilibrium dialysis; muco-adhesion; brain PAMPA; RPMI 2650 nasal epithelial cell}, year = {2021}, eissn = {1999-4923}, orcid-numbers = {Katona, Gábor/0000-0003-1564-4813; Sipos, Bence/0000-0002-0131-4728; Budai-Szűcs, Mária/0000-0001-5187-5702; Balogh, György Tibor/0000-0003-3347-1880; Deli, Mária Anna/0000-0001-6084-6524; Volk, Balázs/0000-0002-2019-1874; Révész, Piroska/0000-0002-5336-6052; Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781} } @article{MTMT:32000163, title = {Improving Oral Bioavailability of Luteolin Nanocrystals by Surface Modification of Sodium Dodecyl Sulfate}, url = {https://m2.mtmt.hu/api/publication/32000163}, author = {Liu, J. and Sun, Y. and Cheng, M. and Liu, Q. and Liu, W. and Gao, C. and Feng, J. and Jin, Y. and Tu, L.}, doi = {10.1208/s12249-021-02012-y}, journal-iso = {AAPS PHARMSCITECH}, journal = {AAPS PHARMSCITECH}, volume = {22}, unique-id = {32000163}, issn = {1530-9932}, abstract = {Luteolin suffers from drawbacks like low solubility and bioavailability, thus hindering its application in the clinic. In this study, we employed sodium dodecyl sulfate (SDS), an efficient tight junction opening agent, to modify the surface of luteolin nanocrystals, aiming to enhance the bioavailability of luteolin (LUT) and luteolin nanocrystals (LNC). The particle sizes of SDS-modified luteolin nanocrystals (SLNC) were slightly larger than that of LNC, and the zeta potential of LNC and SLNC was −25.0 ± 0.7 mV and −43.5 ± 0.4 mV, respectively. Both LNC and SLNC exhibited enhanced saturation solubility and high stability in the liquid state. In the cellular study, we found that SDS has cytotoxicity on caco-2 cells and could open the tight junction of the caco-2 monolayer, which could lead to an enhanced transport of luteolin across the intestinal membrane. The bioavailability of luteolin was enhanced for 1.90-fold by luteolin nanocrystals, and after modification with SDS, the bioavailability was enhanced to 3.48-fold. Our experiments demonstrated that SDS could efficiently open the tight junction and enhance the bioavailability of luteolin thereafter, revealing the construction of SDS-modified nanocrystals is a good strategy for enhancing the oral bioavailability of poorly soluble drugs like luteolin. © 2021, American Association of Pharmaceutical Scientists.}, keywords = {nanocrystals; BIOAVAILABILITY; tight junction; luteolin; Sodium Dodecyl Sulfate}, year = {2021}, eissn = {1530-9932} } @article{MTMT:31655975, title = {Intestinal permeation enhancers to improve oral bioavailability of macromolecules: reasons for low efficacy in humans}, url = {https://m2.mtmt.hu/api/publication/31655975}, author = {Maher, S. and Geoghegan, C. and Brayden, D.J.}, doi = {10.1080/17425247.2021.1825375}, journal-iso = {EXPERT OPIN DRUG DELIV}, journal = {EXPERT OPINION ON DRUG DELIVERY}, volume = {18}, unique-id = {31655975}, issn = {1742-5247}, year = {2021}, eissn = {1744-7593}, pages = {273-300} } @article{MTMT:32024545, title = {Surface charge, glycocalyx, and blood-brain barrier function}, url = {https://m2.mtmt.hu/api/publication/32024545}, author = {Walter, Fruzsina and Santa Maria, Anaraquel and Mészáros, Mária and Veszelka, Szilvia and Dér, András and Deli, Mária Anna}, doi = {10.1080/21688370.2021.1904773}, journal-iso = {TISS BARR}, journal = {TISSUE BARRIERS}, volume = {9}, unique-id = {32024545}, issn = {2168-8362}, year = {2021}, eissn = {2168-8370}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Santa Maria, Anaraquel/0000-0003-3505-5477; Veszelka, Szilvia/0000-0001-8864-1184; Dér, András/0000-0001-6112-884X; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:31335512, title = {The Effect of Sodium Bicarbonate, a Beneficial Adjuvant Molecule in Cystic Fibrosis, on Bronchial Epithelial Cells Expressing a Wild-Type or Mutant CFTR Channel}, url = {https://m2.mtmt.hu/api/publication/31335512}, author = {Gróf, Ilona and Bocsik, Alexandra and Harazin, András and Santa Maria, Anaraquel and Vizsnyiczai, Gaszton and Barna, Lilla and Kiss, Lóránd and Fűr, Gabriella and Rakonczay, Zoltán and Ambrus, Rita and Révész, Piroska and Gosselet, Fabien and Pongsiri, Jaikumpun and Szabó, Hajnalka and Zsembery, Ákos and Deli, Mária Anna}, doi = {10.3390/ijms21114024}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {21}, unique-id = {31335512}, issn = {1661-6596}, year = {2020}, eissn = {1422-0067}, orcid-numbers = {Harazin, András/0000-0002-0904-5606; Santa Maria, Anaraquel/0000-0003-3505-5477; Vizsnyiczai, Gaszton/0000-0003-3245-3736; Rakonczay, Zoltán/0000-0002-1499-3416; Révész, Piroska/0000-0002-5336-6052; Pongsiri, Jaikumpun/0000-0001-9160-2645; Zsembery, Ákos/0000-0003-0253-9379; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:31385933, title = {Development and Characterization of Potential Ocular Mucoadhesive Nano Lipid Carriers Using Full Factorial Design}, url = {https://m2.mtmt.hu/api/publication/31385933}, author = {L. Kiss, Eszter and Berkó, Szilvia and Gácsi, Attila and Kovács, Anita and Katona, Gábor and Soós, Judit and Csányi, Erzsébet and Gróf, Ilona and Harazin, András and Deli, Mária Anna and Balogh, György Tibor and Budai-Szűcs, Mária}, doi = {10.3390/pharmaceutics12070682}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {12}, unique-id = {31385933}, issn = {1999-4923}, year = {2020}, eissn = {1999-4923}, orcid-numbers = {Berkó, Szilvia/0000-0002-3842-8876; Kovács, Anita/0000-0001-5593-1329; Katona, Gábor/0000-0003-1564-4813; Csányi, Erzsébet/0000-0002-3010-1959; Harazin, András/0000-0002-0904-5606; Deli, Mária Anna/0000-0001-6084-6524; Balogh, György Tibor/0000-0003-3347-1880; Budai-Szűcs, Mária/0000-0001-5187-5702} } @article{MTMT:31329545, title = {Graphene Oxide Nanosheets Tailored With Aromatic Dipeptide Nanoassemblies for a Tuneable Interaction With Cell Membranes}, url = {https://m2.mtmt.hu/api/publication/31329545}, author = {Trapani, G. and Caruso, V.C.L. and Cucci, L.M. and Attanasio, F. and Tabbì, G. and Forte, G. and La, Mendola D. and Satriano, C.}, doi = {10.3389/fbioe.2020.00427}, journal-iso = {FRONT BIOENG BIOTECHNOL}, journal = {FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY}, volume = {8}, unique-id = {31329545}, issn = {2296-4185}, keywords = {PEPTIDES; CELLS; FLUORESCENCE; COPPER; AFM; nanostructured materials; viscoelastic properties; Electron Spin Resonance Spectroscopy; Lipid Bilayers; cell culture; Graphene; self-assembly; DICHROISM; Molecular Biology; metal ions; viscoelasticity; Paramagnetic resonance; Photobleaching; fluorescence recovery after photobleaching; Nanosheets; Medical nanotechnology; electron paramagnetic resonance spectroscopy; supported lipid bilayers; supported lipid bilayers; Theranostics; dityrosine; QCM-D; Graphene oxide nanosheets; hybrid nanomaterials; peptide nanotubes; quartz crystal microbalance with dissipation monitoring; diphenylalanine; Peptide aggregation}, year = {2020}, eissn = {2296-4185} } @article{MTMT:31409586, title = {Overcoming negatively charged tissue barriers. Drug delivery using cationic peptides and proteins}, url = {https://m2.mtmt.hu/api/publication/31409586}, author = {Vedadghavami, A. and Zhang, C. and Bajpayee, A.G.}, doi = {10.1016/j.nantod.2020.100898}, journal-iso = {NANO TODAY}, journal = {NANO TODAY}, volume = {34}, unique-id = {31409586}, issn = {1748-0132}, abstract = {Negatively charged tissues are ubiquitous in the human body and are associated with a number of common diseases yet remain an outstanding challenge for targeted drug delivery. While the anionic proteoglycans are critical for tissue structure and function, they make tissue matrix dense, conferring a high negative fixed charge density (FCD) that makes drug penetration through the tissue deep zones and drug delivery to resident cells extremely challenging. The high negative FCD of these tissues is now being utilized by taking advantage of electrostatic interactions to create positively charged multi-stage delivery methods that can sequentially penetrate through the full thickness of tissues, create a drug depot and target cells. After decades of work on attempting delivery using strong binding interactions, significant advances have recently been made using weak and reversible electrostatic interactions, a characteristic now considered essential to drug penetration and retention in negatively charged tissues. Here we discuss these advances using examples of negatively charged tissues (cartilage, meniscus, tendons and ligaments, nucleus pulposus, vitreous of eye, mucin, skin), and delve into how each of their structures, tissue matrix compositions and high negative FCDs create barriers to drug entry and explore how charge interactions are being used to overcome these barriers. We review work on tissue targeting cationic peptide and protein-based drug delivery, compare and contrast drug delivery designs, and also present examples of technologies that are entering clinical trials. We also present strategies on further enhancing drug retention within diseased tissues of lower FCD by using synergistic effects of short-range binding interactions like hydrophobic and H-bonds that stabilize long-range charge interactions. As electrostatic interactions are incorporated into design of drug delivery materials and used as a strategy to create properties that are reversible, tunable and dynamic, bio-electroceuticals are becoming an exciting new direction of research and clinical work. © 2020 Elsevier Ltd}, keywords = {PEPTIDES; TISSUE; PHARMACOKINETICS; SKIN; review; human; Drug Interactions; TISSUES; nonhuman; epithelium; Histology; CATION; drug delivery system; drug carrier; nanoparticle; Cationic peptides; Hydrophobicity; Electrostatics; tendon; mucin; Vitreous Body; hydrogen bond; Positively charged; Skinfold Thickness; Bioenergy; binding energy; membrane permeability; synovium; joint; mucoadhesion; Static Electricity; articular cartilage; ligament; clinical research; clinical trial (topic); gastrointestinal mucosa; peptides and proteins; nucleus pulposus; intervertebral disk; Synergistic effect; Negatively charged; Targeted drug delivery; Targeted drug delivery; Controlled drug delivery; Binding interaction; cell penetrating peptides; negative fixed charge; knee meniscus; stomach mucus; Cationic drug carriers; Cationic protein drug carriers; Electro-diffusive transport; Electrostatic charge interactions; Negatively charged tissues; Charge interactions; Drug delivery materials}, year = {2020}, eissn = {1878-044X} } @article{MTMT:31526166, title = {Adapted nano-carriers for gastrointestinal defense components: surface strategies and challenges}, url = {https://m2.mtmt.hu/api/publication/31526166}, author = {Wang, W. and Yan, X. and Li, Q. and Chen, Z. and Wang, Z. and Hu, H.}, doi = {10.1016/j.nano.2020.102277}, journal-iso = {NANOMED: NANOTECHNOL}, journal = {NANOMEDICINE: NANOTECHNOLOGY BIOLOGY AND MEDICINE}, volume = {29}, unique-id = {31526166}, issn = {1549-9634}, abstract = {Nano-carriers (NCs) provide drugs with protective and oriented strategies. Despite their success in parenteral administration, NCs still need to be optimized to meet the more serious obstacles encountered in the gastrointestinal tract (GIT). The main defense mechanisms include renewing mucus, epithelial obstacles and digestion by GIT segments. These hurdles pose challenges even before NCs target molecules or proteins, which has often led to unsatisfactory delivery efficiency. Therefore, a critical focus is the exemption from negative effects of GIT. A series of adapted NCs have been designed based on surface strategies to form an expected distribution and increase gastrointestinal utilization. In this paper, we review the strategies and efforts of NCs to adapt to gastrointestinal defense components, including the mucus, epithelium and gastrointestinal segments; the related gastrointestinal mechanisms and functions are also summarized synchronously. Last, we discuss the delivery challenges in terms of physiopathological GIT and surface properties of the NCs. © 2020 Elsevier Inc.}, keywords = {MOLECULES; gastrointestinal tract; Drug delivery; defense mechanism; surface property; Network security; Targeted drug delivery; Controlled drug delivery; nano-carriers; Target molecule; Parenteral administration; Nano-carrier; Gastrointestinal barriers; Gastrointestinal response}, year = {2020}, eissn = {1549-9642} } @article{MTMT:30912242, title = {Encapsulation in Polymeric Nanoparticles Enhances the Enzymatic Stability and the Permeability of the GLP-1 Analog, Liraglutide, Across a Culture Model of Intestinal Permeability}, url = {https://m2.mtmt.hu/api/publication/30912242}, author = {Ismail, Ruba and Bocsik, Alexandra and Katona, Gábor and Gróf, Ilona and Deli, Mária Anna and Pannonhalminé Csóka, Ildikó}, doi = {10.3390/pharmaceutics11110599}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {11}, unique-id = {30912242}, issn = {1999-4923}, year = {2019}, eissn = {1999-4923}, orcid-numbers = {Ismail, Ruba/0000-0002-5122-9513; Katona, Gábor/0000-0003-1564-4813; Deli, Mária Anna/0000-0001-6084-6524; Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781} } @article{MTMT:30913424, title = {Transmucosal Absorption Enhancers in the Drug Delivery Field}, url = {https://m2.mtmt.hu/api/publication/30913424}, author = {Maher, Sam and Casettari, Luca and Illum, Lisbeth}, doi = {10.3390/pharmaceutics11070339}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {11}, unique-id = {30913424}, issn = {1999-4923}, abstract = {Drug delivery systems that safely and consistently improve transport of poorly absorbed compounds across epithelial barriers are highly sought within the drug delivery field. The use of chemical permeation enhancers is one of the simplest and widely tested approaches to improve transmucosal permeability via oral, nasal, buccal, ocular and pulmonary routes. To date, only a small number of permeation enhancers have progressed to clinical trials, and only one product that includes a permeation enhancer has reached the pharmaceutical market. This editorial is an introduction to the special issue entitled Transmucosal Absorption Enhancers in the Drug Delivery Field (https://www.mdpi.com/journal/pharmaceutics/special_issues/transmucosal_absorption_enhancers). The guest editors outline the scope of the issue, reflect on the results and the conclusions of the 19 articles published in the issue and provide an outlook on the use of permeation enhancers in the drug delivery field.}, keywords = {vaginal delivery; ORAL DELIVERY; permeation enhancers; nasal delivery; absorption modifying excipients; ocular delivery; transmucosal permeation}, year = {2019}, eissn = {1999-4923}, orcid-numbers = {Maher, Sam/0000-0002-0856-1035; Casettari, Luca/0000-0001-6907-8904} } @article{MTMT:30913423, title = {Surface-layer protein from Lactobacillus acidophilus NCFM attenuates tumor necrosis factor-alpha-induced intestinal barrier dysfunction and inflammation}, url = {https://m2.mtmt.hu/api/publication/30913423}, author = {Wang, Huifang and Zhang, Qiuxiang and Niu, Yuhan and Zhang, Xin and Lu, Rongrong}, doi = {10.1016/j.ijbiomac.2019.06.041}, journal-iso = {INT J BIOL MACROMOL}, journal = {INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES}, volume = {136}, unique-id = {30913423}, issn = {0141-8130}, abstract = {Lactobacillus acidophilus NCFM, a probiotic generally regarded as safe, carries a proteinaceous surface (S) layer, composed of numerous identical subunits (surface layer protein, Slp). S-layer proteins have been confirmed to possess multiple biological properties, but their role in maintaining the intestinal epithelial barrier is not fully known. We investigated the effects of Slp on tumor necrosis factor (TNF)-alpha-elicited intestinal barrier dysfunction and explored the underlying molecular mechanism. TNF-alpha administration markedly induced intestinal epithelial injury and inflammation in Caco-2 cells. Preincubation of Caco-2 cells with Slp at concentrations ranging from 50 to 100 mu pg/mL for 6 h improved intestinal epithelial cell integrity and permeability, restored ZO-1 and Occludin protein expressions (P < 0.05) and reduced the secretion of interleukin 8 by a maximum of 47.8%. Furthermore, the addition of Slp to Caco-2 cell monolayers attenuated cell apoptosis and inhibited nuclear factor-kappa B (NF-kappa B) p65 nucleus translocation by suppressing the activation of NF-kappa B. Collectively, the ability of Slp to attenuate dysfunction of the intestinal epithelial barrier stimulated by TNF-alpha and to exert anti-inflammatory effects supports its potential use in the development of functional foods and in the prevention of inflammatory bowel diseases. (C) 2019 Elsevier B.V. All rights reserved.}, keywords = {Inflammation; CACO-2 CELL MONOLAYERS; Intestinal epithelial barrier; Surface-layer protein; L. acidophilus NCFM}, year = {2019}, eissn = {1879-0003}, pages = {27-34} } @article{MTMT:30913422, title = {Cell-penetrating peptide: a means of breaking through the physiological barriers of different tissues and organs}, url = {https://m2.mtmt.hu/api/publication/30913422}, author = {Xu, Jiangkang and Khan, Abdur Rauf and Fu, Manfei and Wang, Rujuan and Ji, Jianbo and Zhai, Guangxi}, doi = {10.1016/j.jconrel.2019.07.020}, journal-iso = {J CONTROL RELEASE}, journal = {JOURNAL OF CONTROLLED RELEASE}, volume = {309}, unique-id = {30913422}, issn = {0168-3659}, abstract = {The selective infiltration of cell membranes and tissue barriers often blocks the entry of most active molecules. This natural defense mechanism prevents the invasion of exogenous substances and limits the therapeutic value of most available molecules. Therefore, it is particularly important to find appropriate ways of membrane translocation and therapeutic agent delivery to its target site. Cell penetrating peptides (CPPs) are a group of short peptides harnessed in this condition, possessing a significant capacity for membrane transduction and could be exploited to transfer various biologically active cargoes into the cells. Since their discovery, CPPs have been employed for delivery of a wide variety of therapeutic molecules to treat various disorders including cranial nerve involvement, ocular inflammation, myocardial ischemia, dermatosis and cancer. The promising results of CPPs-derived therapeutics in various tumor models demonstrated a potential and worthwhile scope of CPPs in chemotherapy. This review describes the detailed description of CPPs and CPPs-assisted molecular delivery against various tissues and organs disorders. An emphasis is focused on summarizing the novel insights and achievements of CPPs in surmounting the natural membrane barriers during the last 5 years.}, keywords = {DISORDERS; Therapeutic agents; cell penetrating peptides; Membrane transduction}, year = {2019}, eissn = {1873-4995}, pages = {106-124} }