Article
Pharmacology & Pharmacy
Fiona McCartney, Diego R. Perinelli, Mattia Tiboni, Robert Cavanagh, Simone Lucarini, Giovanni Filippo Palmieri, Luca Casettari, David J. Brayden
Summary: The study compared the performance of three monoesters with varying sugar moieties as intestinal permeation enhancers. Results showed that all three esters enhanced permeability in rat intestinal tissue likely via tight junction modulation, while C12-trehalose was slightly less efficacious but also less damaging to the tissue. All three esters have potential for oral formulations as permeation enhancers.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Review
Pharmacology & Pharmacy
Sam Maher, David J. Brayden
Summary: The use of chemical permeation enhancers shows promise in improving oral absorption of low permeability active agents like peptides, but overcoming physiological barriers to achieve significant increases in bioavailability remains a challenge in clinical settings.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Review
Pharmacology & Pharmacy
Sam Maher, Caroline Geoghegan, David J. Brayden
Summary: This article discusses the reasons for sub-optimal bioavailability of macromolecules from PE dosage forms and suggests approaches to improve performance in humans. Optimization of co-localization of the PE with the macromolecule at the epithelial surface is crucial for effective permeation enhancement. Innovative delivery systems have been developed to overcome challenges in achieving optimal co-localization in the GI tract.
EXPERT OPINION ON DRUG DELIVERY
(2021)
Review
Polymer Science
Aneta Ostrozka-Cieslik
Summary: Hormones have gained significant attention as potential drugs for treating various diseases, but formulating hormone-containing drug forms has limitations. This review discusses the development of hydrogels as potential hormone carriers and factors affecting the efficacy of hormones applied to the skin.
Article
Medicine, Research & Experimental
Rosita Kneiszl, Shakhawath Hossain, Per Larsson
Summary: Oral administration of biological drugs faces challenges due to low bioavailability, which can be addressed by formulating drugs with permeation enhancers. Molecular dynamics simulations were used in this study to investigate the impact of six permeation enhancers on model membrane structures, revealing their potential to increase membrane permeability in a concentration-dependent manner. These findings suggest insights for the design of oral dosage forms incorporating permeability enhancer molecules.
MOLECULAR PHARMACEUTICS
(2022)
Article
Multidisciplinary Sciences
Nicholas G. Lamson, Katherine C. Fein, John P. Gleeson, Alexandra N. Newby, Sijie Xian, Kyle Cochran, Namit Chaudhary, Jilian R. Melamed, Rebecca L. Ball, Kanika Suri, Vishal Ahuja, Anna Zhang, Adrian Berger, Dmytro Kolodieznyi, Brigitte F. Schmidt, Gloria L. Silva, Kathryn A. Whitehead
Summary: The study found that strawberry and its red pigment pelargonidin can serve as effective enhancers for oral absorption of macromolecules, with minimal adverse effects and significant bioactivity in mouse models.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Caroline Twarog, Fiona McCartney, Sabine M. Harrison, Brigitte Illel, Elias Fattal, David J. Brayden
Summary: SNAC and C-10 are intestinal permeation enhancers used in formulations of peptides for oral delivery in clinical trials. They have similar mechanisms of action in isolated rat intestinal mucosae, affecting mucosa integrity and interacting with intestinal mucus. Both enhancers have low toxicity and are in agreement with clinical trial data.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Polymer Science
Asif Nawaz, Arshad Farid, Muhammad Safdar, Muhammad Shahid Latif, Shakira Ghazanfar, Nosheen Akhtar, Soad K. Al Jaouni, Samy Selim, Muhammad Waseem Khan
Summary: This research developed a curcumin hydrogel containing natural essential oils as permeation enhancers and demonstrated that suitable natural permeation enhancers can improve the in vitro release and ex vivo permeation and retention of curcumin. Among various natural essential oils, 3% aloe vera oil had the greatest effect on the permeability rate and skin retention of curcumin.
Article
Pharmacology & Pharmacy
David Dahlgren, Tobias Olander, Markus Sjoblom, Mikael Hedeland, Hans Lennernas
Summary: Paracellular permeation enhancers were found to increase the mucosal permeability of hydrophilic peptides with low molecular mass compared to those with a transcellular mechanism-of-action. Additionally, luminal hypotonicity primarily affects paracellular solute transport in the mucosal crypt region.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Cell Biology
Peter Gennemark, Katrin Walter, Niclas Clemmensen, Dinko Rekic, Catarina A. M. Nilsson, Jane Knochel, Mikko Holtta, Linda Wernevik, Birgitta Rosengren, Dorota Kakol-Palm, Yanfeng Wang, Rosie Z. Yu, Richard S. Geary, Stan J. Riney, Brett P. Monia, Rikard Isaksson, Rasmus Jansson-Lofmark, Cristina S. J. Rocha, Daniel Linden, Eva Hurt-Camejo, Rosanne Crooke, Lloyd Tillman, Tina Ryden-Bergsten, Bjorn Carlsson, Ulf Andersson, Marie Elebring, Anna Tivesten, Nigel Davies
Summary: In this study, a chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery was developed and shown to effectively reduce LDL cholesterol levels. Animal experiments demonstrated liver targeting and significant reductions in PCSK9 and LDL cholesterol levels after oral administration.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Katherine C. Fein, John P. Gleeson, Alexandra N. Newby, Kathryn A. Whitehead
Summary: Decades of research on oral peptide drugs have led to clinically successful formulations, often utilizing permeation enhancers to facilitate absorption in the intestines. This study examined the effects of two permeation enhancers on the transport of macromolecules of varying sizes, highlighting their potential to improve the absorption of proteins.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
David J. Brayden, Sam Maher
Summary: The FDA approval of oral semaglutide for type 2 diabetes and oral octreotide for acromegaly demonstrates that selected niche peptides can be administered orally with the use of selected intestinal permeation enhancers. The oral octreotide formulation MYCAPSSA has shown promising results in terms of safety and efficacy, offering acromegaly patients a convenient alternative to monthly depot injections. The Transient Permeation Enhancer technology used in this formulation has shown potential in improving oral absorption of macromolecules.
EXPERT OPINION ON DRUG DELIVERY
(2021)
Article
Polymer Science
Randa Mohammed Zaki, Mohamed A. Ibrahim, Doaa H. Alshora, Amal El Sayeh Abou El Ela
Summary: This study aimed to prepare Span 60-based elastic nanovesicles using the adapted ethanol injection method, and evaluate their ability to improve transdermal permeation of tacrolimus. Different concentrations and types of penetration enhancers were assessed for their impact on the physicochemical properties of the nanovesicles. The results showed significant enhancement in in vitro release compared to pure drug suspension.
Article
Instruments & Instrumentation
Katayoun Morteza-Semnani, Majid Saeedi, Jafar Akbari, Mohammad Eghbali, Amirhossein Babaei, Seyyed Mohammad Hassan Hashemi, Ali Nokhodchi
Summary: The study explored the transdermal permeation enhancing capability of cumin essential oil in nanoemulgel systems containing diclofenac sodium. The nanoemulsion was produced by optimizing HLB values and changing surfactant mixtures. Results showed that the nanoemulgel formulations with cumin essential oil demonstrated higher permeation of diclofenac and stronger antinociceptive effects in mice models compared to simple gel and marketed formulations.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Jacob R. Jorgensen, Lasse H. E. Thamdrup, Khorshid Kamguyan, Line H. Nielsen, Hanne M. Nielsen, Anja Boisen, Thomas Rades, Anette Mullertz
Summary: This study introduces a concept of oral delivery device using elastomeric material to enhance absorption of peptides like insulin. The polydimethylsiloxane foil unfolds in the intestine to closely contact with the intestinal mucosa, increasing peptide absorption. The potential for development of commercially viable biocompatible devices for oral delivery of macromolecules is promising.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Pharmacology & Pharmacy
Sam Maher, Caroline Geoghegan, David J. Brayden
Summary: This article discusses the reasons for sub-optimal bioavailability of macromolecules from PE dosage forms and suggests approaches to improve performance in humans. Optimization of co-localization of the PE with the macromolecule at the epithelial surface is crucial for effective permeation enhancement. Innovative delivery systems have been developed to overcome challenges in achieving optimal co-localization in the GI tract.
EXPERT OPINION ON DRUG DELIVERY
(2021)
Editorial Material
Chemistry, Medicinal
David J. Brayden
Summary: Per Artursson's significant contributions to the field of Caco-2 cells have positioned him as one of the most cited and influential Pharmaceutical scientists of his generation. His research has advanced understanding in key areas such as predictive drug fluxes, intestinal metabolism, and transporter functions, among others.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Caroline Twarog, Fiona McCartney, Sabine M. Harrison, Brigitte Illel, Elias Fattal, David J. Brayden
Summary: SNAC and C-10 are intestinal permeation enhancers used in formulations of peptides for oral delivery in clinical trials. They have similar mechanisms of action in isolated rat intestinal mucosae, affecting mucosa integrity and interacting with intestinal mucus. Both enhancers have low toxicity and are in agreement with clinical trial data.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Hugh E. Giffney, Eoin P. Cummins, Evelyn P. Murphy, David J. Brayden, Daniel Crean
Summary: Adenosine receptors play a crucial role in regulating NR4A expression in myeloid cells, with PKD mediating this process. NF-kappa B also plays a role in regulating NR4A expression, but may not be the central pathway through which AR-stimulation affects NR4A expression.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Pharmacology & Pharmacy
Marilyn N. Martinez, Fang Wu, Balint Sinko, David J. Brayden, Michael Grass, Filippos Kesisoglou, Aaron Stewart, Kiyohiko Sugano
Summary: This article discusses how certain excipients can alter drug oral bioavailability through various in vivo mechanisms. The first part explores the impact of excipients on gastrointestinal absorption, while the second part focuses on evaluating these biological effects through in vitro, in vivo, and in silico methods. Examples are provided to illustrate how these studies can be used to optimize formulations. The article also mentions the application of these tools by the Center for Drug Evaluation and Research to support biowaivers.
Article
Engineering, Biomedical
Neha Shrestha, Yining Xu, Julien R. C. Prevost, Fiona McCartney, David Brayden, Raphael Frederick, Ana Beloqui, Veronique Preat
Summary: Nanoparticle-based oral drug delivery systems have the potential to target inflamed regions in the gastrointestinal tract. This study developed mucus-penetrating nanoparticles to encapsulate monoclonal antibodies for the treatment of inflammatory bowel disease. The results showed that the length of the PEG chain had a significant impact on the efficacy of the nanoparticles in vivo.
ACTA BIOMATERIALIA
(2022)
Review
Pharmacology & Pharmacy
Joseph P. O'Shea, Patrick Augustijns, Martin Brandl, David J. Brayden, Joachim Brouwers, Brendan T. Griffin, Rene Holm, Ann-Christin Jacobsen, Hans Lennernas, Zahari Vinarov, Caitriona M. O'Driscoll
Summary: This article discusses the complexity of oral drug absorption and the importance of evaluating intestinal permeability. It provides a critique of in vivo, in vitro, and ex vivo approaches for assessing drug permeability. Continued improvement and validation of in silico models will enhance early characterization of permeability and facilitate absorption modeling.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Sadaf Ejaz, Bridget Hogg, Delyan R. Hristov, David J. Brayden, Muhammad Imran, Sourav Bhattacharjee
Summary: Crosslinked chitosan nanocarriers entrapping coumarin-6 with or without surface mannosylation were synthesized and evaluated for their cytotoxicity, cellular uptake, permeation, and mucin adhesion. Results showed that mannosylated and non-mannosylated nanocarriers exhibited similar biocompatibility in cell experiments, but differed in cellular uptake. Additionally, chitosan nanocarriers enhanced adhesion to porcine gut mucin through increased cationic charge density.
Article
Chemistry, Multidisciplinary
Patrik Lundquist, Georgiy Khodus, Zhigao Niu, Lungile Nomcebo Thwala, Fiona McCartney, Ivailo Simoff, Ellen Andersson, Ana Beloqui, Aloise Mabondzo, Sandra Robla, Dominic-Luc Webb, Per M. Hellstroem, asa Keita, Eduardo Sima, Noemi Csaba, Magnus Sundbom, Veronique Preat, David J. Brayden, Maria Jose Alonso, Per Artursson
Summary: Peptide drugs are not orally bioavailable due to their poor stability and permeability, but nanoparticle formulations may provide a solution. In this study, the absorption mechanisms of four insulin-loaded arginine-rich nanoparticles were investigated. One nanoparticle showed significant uptake and is proposed for further investigation for local delivery.
Article
Oncology
David J. Brayden
Summary: The clinical translation of orally administered macromolecules for systemic delivery is limited, but local delivery of macromolecules for treating inflammatory bowel conditions has shown promise. Currently, only a few orally administered peptide products have gained FDA approval, while locally delivered macromolecules for gut-targeted therapy have reached clinical trials.
Article
Pharmacology & Pharmacy
Caroline Twarog, Elias Fattal, Magali Noiray, Brigitte Illel, David J. Brayden, Myriam Taverna, Herve Hillaireau
Summary: This study compares the biophysical interactions between exenatide and C-10 or SNAC, finding that specific supramolecular structures are formed and non-specific interactions dominate the binding process. Bile salts in the gastrointestinal lumen inhibit the interaction between these permeation enhancers and exenatide.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Shane Forde, Giulianna Vozza, David J. Brayden, Hugh J. Byrne, Jesus M. Frias, Sinead M. Ryan
Summary: In order to address the challenges of oral administration of SeMet, researchers encapsulated it in zein-coated nanoparticles made from chitosan using an ionic gelation formulation. The SeMet-NPs showed high stability and minimal cytotoxicity, as well as antioxidant properties. Additionally, they exhibited increased intestinal permeability compared to free SeMet. These findings suggest the potential of SeMet-NPs for further development as an oral supplement.
Review
Pharmacology & Pharmacy
Mirko Koziolek, Patrick Augustijns, Constantin Berger, Rodrigo Cristofoletti, David Dahlgren, Janneke Keemink, Paer Matsson, Fiona McCartney, Marco Metzger, Mario Mezler, Janis Niessen, James E. Polli, Maria Vertzoni, Werner Weitschies, Jennifer Dressman
Summary: This review discusses various methodologies used to determine drug permeability in the human gastrointestinal tract, including in vitro, in silico, and in vivo approaches. It highlights advancements in novel techniques such as computational approaches and gut-on-chip models. The review also explores the impact of permeability estimations on PK predictions and the importance of drug permeability in clinical studies.
Article
Biochemistry & Molecular Biology
Minna Khalid Danish, John P. Gleeson, David J. Brayden, Hugh J. Byrne, Jesus M. Frias, Sinead M. Ryan
Summary: This study demonstrates the potential of chitosan-zein nanoparticles as an oral delivery system for the encapsulation of IPP and LKP, showing their effectiveness in reducing blood pressure.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)