An On-Demand Triggered Release System for Protecting the Skin from Ultraviolet Light

Abstract

Aims: This thesis aimed to develop photosensitive liposomes for on-demand delivery of entrapped ultraviolet (UV) filters for skin protection. It was hypothesized that liposomes with suitable size would have limited skin penetration, reducing potential for systemic toxicity, and the photosensitivity would allow UV filters to be released upon exposure to sunlight. Specific objectives were to: i) develop a simultaneous assay for hydrophilic and lipophilic UV filters; ii) prepare, characterize, and evaluate the skin permeation, retention, and deposition characteristics of photosensitive liposomes; iii) develop a bioadhesive hydrogel suitable for topical applications; iv) investigate the photoprotective effects of the photosensitive liposomes. Methods: 1,2-Bis(4-(n-butyl)phenylazo-4'-phenylbutyroyl)phosphatidylcholine (BisAzo-PC) was synthesized and used to formulate photosensitive liposomes which were physically characterized. To achieve this, a validated HPLC assay was developed. Drug permeation, retention, and deposition characteristics was investigated using porcine skin. A 32 factorial design was used to formulate a bioadhesive binary hydrogel. A fibroblast model was used to evaluate photoprotective properties. The universal Sun Protect Factor (uSPF) was also measured. Results and Discussion: Liposomes with optimal characteristics were formulated from hydrogenated soy phosphatidylcholine, cholesterol, and BisAzo-PC, and achieved modest entrapment efficiency and drug loading. Permeation, retention, and deposition studies identified minimal permeation of UV filters through the epidermis and localization of the liposomes in the stratum corneum. A binary hydrogel consisting of 12% hydroxypropyl methylcellulose and 6% polyvinylpyrrolidone was identified to have favorable texture properties and adhesiveness. The hydrogel could impair the release of benzophenone-4. This effect is theorized to be due to the polymer forming complexes with negatively charged molecules, holding the molecule within the matrix. Photoprotective properties of the formulation indicated the capacity of the photosensitive liposome-in-gel to reduce reactive oxygen species generated by fibroblasts when exposed to UV irradiation. uSPF values corroborated this finding with the formulation at 38.1 ± 1.1, exceeding that of a commercial sunscreen. However, some cell death was observed 24 hours after irradiation, indicating the delayed damage. Conclusions: Benzophenone-4 and octocrylene were simultaneously encapsulated into photosensitive liposomes, and proven to have limited skin penetration. Liposomes suspended in the binary gel could provide sustained protection against UV irradiation.