Vanessa Dartora: Chitosan Hydrogels Containing MK2 inhibitor peptide-Loaded Nanoparticles to Facilitate Percutaneous Absorption and Dampen Local Inflammation for Atopic Dermatitis Treatment
SEMINAR (Zoom)
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Speaker
Vanessa Franco Carvalho Dartora
9:25 am via ZOOM
Title: Chitosan Hydrogels Containing MK2 inhibitor peptide-Loaded Nanoparticles to Facilitate Percutaneous Absorption and Dampen Local Inflammation for Atopic Dermatitis Treatment
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited treatment options. Topical corticosteroids are the first-line treatment to control moderate-to-severe AD; however, their prolonged application can result in dermal atrophy. In this study, the MK2-inhibitor peptide YARA (YARAAARQARAKALNRQGLVAA) was encapsulated into pNIPAM nanoparticles (NP), which were incorporated into chitosan hydrogels to promote local drug delivery, improve moisture and suppress inflammation, while reducing adverse side effects. Hollow thermoresponsive pNIPAM NPs were synthesized via degradation of a N,N′-bis (acryloyl)cystamine (BAC) cross-linked core and the polyvinyl alcohol (PVA)/ Chitosan hydrogel was obtained using the freeze-thaw method. The NPs showed a mean diameter of 361.5 ± 4.6 nm, negative ζ potential (-28.3 mV), high loading efficiency (>50%) and no cytotoxic activity in human fibroblasts and keratinocytes, suggesting their safety for topical applications. Nanoparticles improved the release kinetics of YARA when compared to the nonencapsulated peptide (up to 120 h release). The NPs and hydrogels delivered 2 and 4-fold, respectively, more YARA into viable layers of porcine skin in vitro 12 h post-application than the nonencapsulated compound in intact and impaired barrier conditions. Furthermore, the NPs treatment decreased the levels of IL-1, TNF-, INF-y and IL-10 up to 9 times compared to non-treated human keratinocytes after the induction of inflammation. Consistent with the results in cell culture, the nanoencapsulation YARA in NP further reduced the levels of IL-1, IL-8, IL-6 and INF-y up to 14 times in an ex vivo skin culture model after induction of inflammation with Lipopolysaccharide from Escherichia coli (LPS). Our data suggest that YARA loaded nanoparticles incorporated into chitosan hydrogel is a promising formulation strategy for topical treatment of AD.
BIO
Dr. Vanessa Dartora is a pharmacist that received her Master and Ph.D. at the University of São Paulo, Brazil in the Department of Pharmacology. She has focused her research on the development of nanostructured and / or nanoparticulate delivery systems to modify the distribution profile and promote the co-localization of multiple drugs at specific sites (skin and breast tissue), associating the increase in effectiveness with the reduction of adverse effects. Dr. Dartora is a Postdoctoral fellow at Biomedical Engineering Department from UC Davis since February 2021. Her currently projects include the development and evaluation of polymeric nanoparticles to promote an effective delivery of pharmaceuticals through the skin. Recently, she was accepted in the UC Davis Stem Cell Training Program working with bioorganic chemistry and bioconjugate chemistry to engineer glycosaminoglycans and proteoglycan mimetics for tissue healing and regeneration. Dr. Dartora is a member of the American Association of Pharmaceutical Sciences (AAPS), Brazilian Association of Pharmaceutical Sciences (ABCF) and the Biomedical Engineering Society (BME) since 2018. In 2021 she won Best Poster Presentation prize (1st Place) at the 27th Annual Cancer Research Symposium poster – UC Davis Comprehensive Cancer Center, and, in 2022, the best Poster Presentation at the 7th Annual Postdoctoral Research Symposium-2022 (PRS-2022).
