Acne is a chronic dermatological disease of pilosebaceous units existing in the form of hair follicles (HFs) and accompanying sebaceous glands. In topical acne treatment, localisation of drug substance at the target site, in pilosebaceous units, especially in HFs is essential. The aims of this study were to develop and optimise adapalene (ADA)-loaded PAMAM dendrimer-based nanocarriers for topical acne treatment and to prepare gel formulations of the selected nanocarriers and to characterise their rheological properties and spreadability. ADA accumulation in HFs and in the skin from PAMAM dendrimers' aqueous colloidal formulations and their gel formulations were quantitatively determined using punch biopsy technique. Follicular targeting efficiency from PAMAM dendrimers and their gel formulation was compared with the commercial gel product, Differin® Gel. The localisation of fluorescently labelled PAMAM dendrimers was visualised using a confocal microscope, which confirmed a successful delivery of the carrier system to the HFs. It was also quantified that PAMAM dendrimers improved follicular localisation and skin deposition of ADA. PAMAM dendrimers' gel formulation including lower ADA doses compared with the commercial product exhibited efficient performance in terms of drug accumulation in HFs. In vitro cell viability studies showed the relative safety of G2-PAMAM dendrimers which could be considered to possibly be well tolerated by the skin. Overall, PAMAM dendrimers' potential to selectively target drugs to the site of action, reduce dose administrated, therefore minimise side effects and provide efficiency in topical treatment of dermatological diseases such as acne was shown.
Keywords: Acne; Adapalene; Dermal delivery; Follicular targeting; Nanocarriers; PAMAM dendrimers; Punch biopsy.