Abstract
The study focused to optimize, evaluate and investigate mechanistic perspective of ketoconazole (KTZ) loaded solid lipid nanoparticles (KTZ-SLNs) for enhanced permeation across rat skin. KTZ-SLNs were evaluated for size, distribution, zeta potential (ZP), percent entrapment efficiency (%EE), drug release, morphology, thermal behavior (DSC), compatibility (FTIR) and solid state characterization (X-ray diffraction, XRD). Moreover, ex-vivo permeation and drug deposition into rat skin were conducted using Franz diffusion cell. Mechanistic evaluations were confirmed using confocal laser scanning microscopy and vibrational ATR methods using EpiDermTM model. An in vivo dermatokinetics study was performed to ensure KTZ access to the dermal region. Accelerated and photostability studies were conducted at different temperatures (0, 30, and 40 °C) for 12 months. The spherical optimized KOF1 showed optimal particle size (291 nm), and high negative ZP (-27.7 mV). Results of FTIR, DSC, and XRD confirmed compatibility of KTZ with excipients, purity of KTZ & dissolved KTZ in lipid matrix, and amorphous nature of KTZ-SLNs. In-vitro release was found to be slow and sustained whereas ex vivo permeation parameters were significantly high in KTZ-SLNs as compared to drug suspension and marketed product. Drug retention was 10- and -5 fold higher than KTZ-SUS and marketed product, respectively. Pharmacokinetic parameters were improved by SLNs formulation. Confocal raman spectroscopy experiment showed that KTZ-SLNs could penetrate beyond the human stratum corneum into viable epidermis. Fluorescent microscopy confirmed improved penetration of KTZ-SLNs was through human follicular pathway. KTZ-SLNs stable over 12 months under set conditions.
Nanotechnology in Wound Healing; Semisolid Dosage Forms Containing Curcumin-Ampicillin Solid Lipid Nanoparticles, in-Vitro, Ex-Vivo and in-Vivo Characteristics
