Evaluation of nano-sized dendritic structures for dermal drug targeting

Acne is a chronic dermatological disease of pilosebaceous units consisting of hair follicles and accompanying sebaceous glands. In its topical treatment, drug localization at the target site, in pilosebaceous units, especially in hair follicles is essential. In this thesis; development, optimization and characterization studies of adapalene loaded PAMAM dendrimer and dendron-based micelle (DM) nanocarriers for topical acne treatment were conducted. Gel formulations of the selected dendritic nanocarriers were also prepared, rheological properties and spreadability were investigated. Adapalene accumulation in hair follicles and in the skin from PAMAM dendrimers' and DMs' aqueous colloidal formulations and their gel formulations were quantitatively determined using punch biopsy technique. Follicular targeting efficiency of the nanocarriers and their gel formulations was compared with the commercial gel product. The localisation of fluorescently labeled PAMAM dendrimers and the fluorescent dye from DMs loaded with fluorescent Nile Red was visualized using confocal microscope. In vitro adapalene release from polymer-dendron conjugates (PDC-ADA), constructed by covalent conjugation of adapalene to dendron structures, was evaluated. The localised amounts of PDC-ADA and adapalene released from the conjugates within the skin quantitatively determined. In conclusion, it was determined that dendritic nanocarriers improved follicular localization and skin deposition of adapalene. The dendritic nanocarriers' gel formulations including lower adapalene doses compared to the commercial product, exhibited efficient performance in terms of drug accumulation in hair follicles. Dendritic nanocarriers' potential to selectively target drugs to the site of action, reduce dose administration, therefore minimize side effects in topical treatment of dermatological diseases such as acne was shown. Key Words: PAMAM dendrimer, dendron micelle, skin, hair follicle, acne