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PermeaPad

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PermeaPad is a biomimetic barrier technology that was initially developed in 2013 by Dr. Massimiliano Pio di Cagno and Dr. Annette Bauer-Brandl at the University of Southern Denmark.[1]. Since 2016, PermeaPad has been available as a commercial product. This technology is designed for conducting drug permeability tests without relying on animal models.

The fundamental concept behind PermeaPad is to create an artificial, non-animal barrier that simulates the permeability of drugs. Originally, PermeaPad pads were developed for large-scale diffusion cells such as Franz cells or side-by-side cells to investigate the apparent permeability (Papp) of drugs through the gastrointestinal tract[2]. Later, this technology was adapted to a 96-well plate configuration for high-throughput testing.

PermeaPad GIT Barrier

The barrier consists of a liposomal gel[3] that spontaneously forms upon hydration and is sandwiched between two layers of regenerated cellulose. What sets PermeaPad GIT barrier apart from other tests is its unique resistance to chemical and mechanical stress, making it particularly suitable for formulation testing. The barrier is compatible with a wide range of surfactants and co-solvents, including Polysorbate 80, DMSO, and Triton-X, even at high concentrations[4].

Of particular interest is PermeaPad's compatibility with various biorelevant media such as FaSSIF, FaSSIF-V2, FeSSIF, and FeSSIF-V2. The barrier also takes into account paracellular transport, contributing to its biomimetic nature[5].

The applications of PermeaPad are diverse and include compound screening, pre-formulation tests, food effect studies, as well as dissolution and permeation assays. These tests can be performed either in 96-well plates or in various permeation setups, including vertical diffusion cells, side-by-side cells, and others.

Applying mucus to PermeaPad GIT barrier enhances its biomimetic properties. This makes the barrier suitable for studying in vitro nasal[6] and pulmonary drug delivery systems[7], in addition to oral formulations.

PermeaPad Skin Barrier

Recently the suitability of the PermeaPad Skin barrier for drug permeation testing was explored as an alternative to human and animal skin models. The limitations of using porcine skin and the ethical concerns surrounding animal models have prompted the development of biomimetic barriers as potential alternatives for transdermal testing. The barrier is designed to replicate the stratum corneum and consists of a lipid mixture between layers of regenerated cellulose and a porous filter[8]

Conclusion

Overall, PermeaPad offers an avenue for conducting drug permeability tests without relying on animal models. The combination of biomimetic nature, chemical resistance, and adaptability to different test setups makes it a tool in pharmaceutical research and development.

References

  1. "WIPO - Search International and National Patent Collections". patentscope.wipo.int. Retrieved 2023-08-21.
  2. di Cagno, Massimiliano; Bibi, Hanady A.; Bauer-Brandl, Annette (2015-06-20). "New biomimetic barrier Permeapad™ for efficient investigation of passive permeability of drugs". European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences. 73: 29–34. doi:10.1016/j.ejps.2015.03.019. ISSN 1879-0720. PMID 25840123.
  3. Brandl, M.; Tardi, C.; Drechsler, M.; Bachmann, D.; Reszka, R.; Bauer, K. H.; Schubert, R. (1997-03-17). "Three-dimensional liposome networks: freeze fracture electron microscopical evaluation of their structure and in vitro analysis of release of hydrophilic markers". Advanced Drug Delivery Reviews. 24 (2): 161–164. doi:10.1016/S0169-409X(96)00455-3. ISSN 0169-409X.
  4. Bibi, Hanady Ajine; di Cagno, Massimiliano; Holm, Rene; Bauer-Brandl, Annette (2015-09-30). "Permeapad™ for investigation of passive drug permeability: The effect of surfactants, co-solvents and simulated intestinal fluids (FaSSIF and FeSSIF)". International Journal of Pharmaceutics. 493 (1–2): 192–197. doi:10.1016/j.ijpharm.2015.07.028. ISSN 1873-3476. PMID 26192628.
  5. Eriksen, Jonas Borregaard; Barakat, Hesham; Luppi, Barbara; Brandl, Martin; Bauer-Brandl, Annette (April 2022). "Modulation of Paracellular-like Drug Transport across an Artificial Biomimetic Barrier by Osmotic Stress-Induced Liposome Shrinking". Pharmaceutics. 14 (4): 721. doi:10.3390/pharmaceutics14040721. ISSN 1999-4923. PMC 9027509 Check |pmc= value (help). PMID 35456555 Check |pmid= value (help).
  6. Corazza, Elisa; di Cagno, Massimiliano Pio; Bauer-Brandl, Annette; Abruzzo, Angela; Cerchiara, Teresa; Bigucci, Federica; Luppi, Barbara (2022-12-01). "Drug delivery to the brain: In situ gelling formulation enhances carbamazepine diffusion through nasal mucosa models with mucin". European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences. 179: 106294. doi:10.1016/j.ejps.2022.106294. ISSN 1879-0720. PMID 36116696 Check |pmid= value (help). Unknown parameter |s2cid= ignored (help)
  7. Butnarasu, Cosmin; Garbero, Olga Valentina; Petrini, Paola; Visai, Livia; Visentin, Sonja (2023-01-22). "Permeability Assessment of a High-Throughput Mucosal Platform". Pharmaceutics. 15 (2): 380. doi:10.3390/pharmaceutics15020380. ISSN 1999-4923. PMC 9966667 Check |pmc= value (help). PMID 36839702 Check |pmid= value (help).
  8. Magnano, Greta Camilla; Sut, Stefania; Dall'Acqua, Stefano; Di Cagno, Massimiliano Pio; Lee, Luke; Lee, Ming; Larese Filon, Francesca; Perissutti, Beatrice; Hasa, Dritan; Voinovich, Dario (2022-11-25). "Validation and testing of a new artificial biomimetic barrier for estimation of transdermal drug absorption". International Journal of Pharmaceutics. 628: 122266. doi:10.1016/j.ijpharm.2022.122266. hdl:11368/3032698. ISSN 0378-5173. PMID 36228883 Check |pmid= value (help). Unknown parameter |s2cid= ignored (help)


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