Selective delivery of adapalene to the human hair follicle under finite dose conditions using polymeric micelle nanocarriers

Abstract

Drug delivery systems that target the pilosebaceous unit (PSU) selectively could improve the clinical management of diseases that originate in the hair follicle. The aims of this study were (i) to prepare polymeric micelles using d-α-tocopheryl polyethylene glycol succinate diblock copolymer that incorporated adapalene (ADA), a retinoid indicated for Acne vulgaris, and (ii) to investigate the feasibility of delivering ADA preferentially to the PSU under finite dose conditions - thereby better approximating actual conditions of use by patients. Incorporation of ADA into spherical micelles (d <20 nm) increased aqueous solubility by ∼50 000-fold (from <4 ng mL to 0.2 mg mL). Optimized micelle solution and gel formulations (0.02% ADA) were stable after storage for 4 weeks at 4 °C. Finite dose experiments using full-thickness porcine and human skin revealed that ADA delivery efficiency from micelle solution and gel formulations was equivalent and was >2- and 10-fold higher than that from Differin® gel and Differin® cream (products containing ADA at 0.1% (w/w)). Follicular delivery studies in human skin, using a punch biopsy technique to extract the intact PSU, demonstrated that the micelle solution and gel formulations did indeed enable preferential delivery of ADA to the PSU (4.5- and 3.3-fold higher, respectively, than that to PSU-free skin biopsies). Confocal laser scanning microscopy provided visual corroboration that ADA was uniformly distributed in the hair follicles. In conclusion, the results confirmed that polymeric micelle nanocarriers enabled selective, targeted drug delivery to the PSU under finite dose conditions and so might improve therapy of follicular diseases and decrease off-site side-effects.

Recent Advances Regarding the Therapeutic Potential of Adapalene

“…The obtained results (in vitro and ex vivo) were auspicious in terms of delivery of hydrophobic drug and reduction of skin irritation [ 132 ]. Additionally, ADP was incorporated in polymeric micelles, based on d-α-tocopheryl polyethylene glycol succinate diblock copolymer with in vitro promising results [ 133 ].…”

Targeted Topical Delivery of Retinoids in the Management of Acne Vulgaris: Current Formulations and Novel Delivery Systems

“…Adapalene has physicochemical properties that limit its bioavailability in the skin and appendages, in particular its high lipophilicity and pKa 4.23 (Table 2). Colloidal delivery approaches utilising both lipid and solid-based formulations have been investigated to target adapalene delivery to the pilosebaceous units [83,84,85,86,87,88,89,90,91].…”

Advanced development of a non-ionic surfactant and cholesterol material based niosomal gel formulation for the topical delivery of anti-acne drugs

“…ADP showed poor therapeutic applications clinically because it causes irritation of the skin, dryness, a burning or stinging sensation, peeling/ exfoliation and photosensitivity with pigmentation. To overcome these limitations, various approaches have been studied such as liposomes, 5 TyroSpheres, 6 polymeric micelles 7 and hydrogel matrices 8 to control and improve the ADP permeation. Nanovesicles have shown huge potential in topical delivery due to their advantages such as prolonged therapeutic effect and avoidance of the entry of the drug into the systemic circulation, thereby controlling the side effects.…”