Allahyani, Eman; (2023) Design and Development of Phytonanoformulations for Acne Vulgaris Treatment. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Introduction: Acne vulgaris is a chronic inflammatory skin condition that primarily affects pilosebaceous units. Through the development and characterisation of nanotechnology-based formulations for the topical delivery of phytochemicals and retinoic acid, this study has addressed the known challenges of poor solubility and stability associated with these compounds. Methods: In this research, retinoic acid-chitosan oligosaccharides (RA-ChiOS) conjugate was synthesised via a coupling reaction. This conjugate was used to incorporate Cleome chrysantha Decne methanolic extract, quercetin, gallic acid, and rosmarinic acid. Through evaluations of their anti-acne properties, the suitability of the obtained formulations as potential treatments for acne vulgaris was established. In addition, retinoic acid was encapsulated with various amphiphilic carriers, either as simple micelles of TPGS and HS15 or mixed micelles of TPGS/or HS15 with Pluronic F127 and TPGS/ HS15 using the film hydration technique. Following short-term storage under defined conditions, the resultant products were characterised and evaluated. Results: FTIR and 1H NMR analysis demonstrated the effective synthesis of the RA-ChiOS conjugate. Micelles generated from RA-ChiOS had a mean particle size of 185.6 ±1.47 nm and an overall positive surface charge. Encapsulation of phytochemicals had variable effects on particle size but had no effect on surface charge (p ˃0.05). After evaluating phytochemicals' antioxidant, cytotoxic, antimicrobial, and anti-inflammatory properties, it became apparent that encapsulation significantly increased their efficacy compared to their free form. Furthermore, the study revealed that mixed micelles of TPGS/HS15 was higher than single and other mixed micelles in terms of encapsulation efficacy and stability as retinoic acid carriers. Conclusions: This research effectively improved the anti-acne properties of RA-ChiOS micelles by encapsulating phytochemicals, resulting in enhanced antioxidant activity, anti-microbial efficacy against C. acnes, and anti-inflammatory effects, while maintaining high biocompatibility. In addition, the use of TPGS/HS15 has emerged as a promising strategy for incorporating and delivering retinoic acid, as it offers improved solubility and stability.

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