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theses

The importance of nanotechnology in the field of drug delivery has been dramatically increased and nanocarriers are finding potential applications in many areas of medicine. The unique physico-chemical properties of nanoparticles allow them to overcome some biological barriers and hence, improve the bioavailability of their payload. In this thesis, a platform technology has been described based on amphiphilic biocompatible ABA triblock copolymers that self-assemble to form polymeric nanomicelles (TyroSpheres) to address the need of a suitable carrier system for enhancing the topical delivery of lipophilic actives and their solubility as well as stability in the formulation. Our goal was to investigate the applicability of TyroSpheres for follicular drug delivery and develop an aqueous-based gel formulation of drug-TyroSphere for acne therapy. In addition, we explored other biological properties of this carrier system for drug delivery, including cytotoxicity, genotoxicity and skin irritation to ensure the safety of the carriers/formulation for short-term and long-term applications. Our selected anti-acne drug was adapalene, a third generation retinoid with a logP of 8.2. Adapalene-TyroSphere formulations were characterized for carrier particle size, binding efficiency, drug loading, drug release, sebum partitioning, crystallinity, and finally follicular delivery. Gel formulations of adapalene-TyroSpheres were also prepared using different thickening agents and analyzed for content uniformity, rheology, particle agglomeration and skin irritation. A preclinical mouse acne model was employed to test the efficacy of the adapalene treatment via TyroSpheres and compare it with the commercial product, Differin®. Another highly lipophilic active that was formulated with TyroSpheres was Vitamin D3, which is sensitive to many environmental factors and hence, is an unstable compound. TyroSpheres were able to protect Vitamin D3 against hydrolysis and photodegradation and significantly enhance the stability of this active in the aqueous formulation. In summary, our findings show that TyroSpheres lack short-term cytotoxicity and genotoxicity. These nanoparticles can accumulate in hair follicles and enhance drug delivery through intercellular and follicular pathways, which can benefit treatment of dermatological disorders, such as acne. The comedolytic properties of the retinoid were preserved after being encapsulated in TyroSpheres. The novel oil-free and alcohol-free aqueous-based formulation of adapalene can be potentially used in management of acne by delivering the drug where the disease originates, while reducing drug/vehicle-related skin irritation.

ETD_7131

Ph.D.

Includes bibliographical references

by Tannaz Ramezanli

doi:10.7282/T3NC63C7

ETD doctoral

The author owns the copyright to this work.