TitlePolymeric nanospheres for skin penetration enhancement
NameBatheja, Priya B. (author), Michniak-Kohn, Bozena (chair), Minko, Tamara (internal member), You, Goufeng (internal member), Dayan, Nava (outside member), Rutgers University, Graduate School - New Brunswick,
Polymeric drug delivery systems,
DescriptionResearch and development in the field of topical and transdermal delivery has been particularly challenging due to the tough penetration barrier provided by the stratum corneum, the superficial skin layer. Nano-sized vesicles can potentially act as carriers to skin layers without causing the toxicity and irritation associated with chemical and physical skin penetration enhancers. In this study we have characterized the skin penetration potential of polymeric nanospheres made from amphiphilic ABA-triblock co-polymers that are biocompatible, biodegradable and bind efficiently to hydrophobic molecules. We evaluated the delivery of hydrophobic and poorly water soluble compounds via these nanospheres into different skin layers and found significant enhancement in their delivery to the epidermal-dermal junction and to the dermis. Thus, these nanospheres have tremendous potential for targeting diseases such as acne, psoriasis and eczema that have their origins in these layers. Formulation of the nanospheres in hydrophilic gels, alone and in combination with a chemical skin penetration enhancer significantly increased the penetration of complexed molecules in vitro in human skin and in vivo in porcine skin. We also evaluated the delivery profiles of these nanospheres in a bioengineered Human Skin Equivalent (HSE). The full thickness HSE was developed from a combination of human derived cells and extra-cellular components and cultured with a novel media cocktail to strengthen the permeability barrier. The HSE was characterized for the permeability profiles of agents with differing physiochemical properties and was found to be more permeable than human skin, but similar to the commercially available skin equivalent EpidermFT®. The HSE also served as an effective model for evaluation of phototoxicity of topically applied agents, and was able to correctly predict the phototoxic potential of compounds when evaluated against a validated in vitro cell-based method. When used for evaluation of the skin delivery potential of nanosphere formulations, the penetration enhancement ratios in the HSE were similar to those obtained in human skin and porcine skin, although the amount and depth of skin penetration of compounds was different. Thus, despite a weaker permeability barrier, the HSE can serve as a reproducible model for pre-screening of the skin delivery properties of formulations.
NoteIncludes bibliographical references (p. 237-247)
Noteby Priya B. Batheja
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.