Hydrogel containing adapalene- and dapsone-loaded lipid-core nanocapsules for cutaneous application: development, characterization, in vitro irritation and permeation studies

Lipid-core polymeric nanocapsule suspensions containing adapalene and dapsone (AD-LCNC) were developed and incorporated in a Carbopol 940 (R) hydrogel (AD-LCNC HG). A nanoemulsion (AD-NE), similarly prepared but omitting the polymer, was developed and also incorporated in a Carbopol 940((R)) hydrogel (AD-NE HG) to evaluate the polymer effect. Physicochemical characteristics were evaluated. AD-LCNC suspensions containing 0.07% of dapsone and 0.025% of adapalene presented an average size of 194.9 +/- 0.42nm, zeta potential of -15 +/- 1.2mV and polydispersity index of 0.12 +/- 0.02, using electrophoretic light scattering (n=3). The granulometric profiles showed unimodal size distributions for AD-LCNC suspensions, demonstrating that no microscopic population is present in the formulation. No instability phenomena were observed by multiple light-scattering analysis. Photomicrographs obtained by TEM showed homogeneous- and spherical-shaped particles. The encapsulation efficiency was 99.99% for dapsone and 100% for adapalene. The pH values for AD-LCNC suspensions were 5.1 and 7.6 for AD-LCNC HG. Formulations were classified as nonirritant in the HET-CAM test. Rheological analysis demonstrated a non-Newtonian pseudoplastic profile. The in vitro skin permeation studies showed a higher amount of adapalene in epidermis (130.52 +/- 25.72ng/mg) and dermis (4.66 +/- 2.5ng/mg) for AD-NE HG. The AD-LCNC HG presented higher amount of dapsone in both the skin layers (73.91 +/- 21.64ng/mg in epidermis and 4.08 +/- 0.85ng/mg in dermis). The assay showed significant difference between AD-LCNC HG and AD-NE HG (p<0.05), and drug was not found in the receptor medium.