Acid-responsive Polymeric Nanocarriers For Topical Adapalene Delivery

Acne vugaris is a common disease which affects about80%of teenagers.Theacne skin is characteristic of a relatively lower pH microenvironment in contrast tothe healthy skin. Such pH discrepancy can be used as a site-specific trigger foron-demand topical drug delivery. Adaplene is the third-genneration retinoid whichhas been widely used for topical acne treatment; however, the dose-dependent andvehicle-dependent irritation of the commercial available dosage form often leads tothe poor patient compliance. When encapsulated adapalene in acid-responsivepolymer, the rapid delivery of high concentration of the drug to the application sitecan be eliminated and the on-demand adapalene release can be achieved ultilizing theacid microenvieronment of acne skin. The adapalene-loaded nanoparticle wasprepared via the nanoprecipitation process with Eudragit EPO and poly (vinylalcohol) as the carrier and stablilizer respectively. The drug loading was3.5±0.3%(w/w) which was determined by high performance liquid chromatography (HPLC).The adaplene-loaded nanoparticles showed a spherical morphology with a sizeof125.8±3.5nm and a positive charged surface of18.4±2.9mV via dynamiclight scattering.The nanoparticles were also characterized via X-ray diffraction(XRD), differential thermal analysis (DTA) and Fourier transform infraredspectroscopy (FTIR) to prove the presence of hydrogen bonding between thedrug and the carrier. The drug release study demonstrated a rapid adapalene releaseat pH4.0compared to that at pH5.0and6.0. The permeation study revealed asignificant higher drug flux from the adapalene-loaded nanoparticle (6.5±0.6μg.cm-2.h-1) in comparison to that (3.9±0.4μg.cm-2.h-1) in the control vehicle(Transcutol) when using silicone membrane.The in vitro pig skin permeation study,together with the tape stripping study showed that adapalene-loaded nanoparticle candeliver the same amount of drug to the stratum corneum as the control vehicle(Transcutol) did.This paper confirmed that the acid-responsive adapalene nanocarrier cansignificantly improve the efficiency of drug delivery, reduce the skin irritation andimprove the therapy.