Solid Lipid Nanoparticles for Oral Delivery of Decitabine: Formulation Optimization, Characterization, Stability and Ex-Vivo Gut Permeation Studies

摘要

The aim of current study was to develop solid lipid nanoparticles (SLNs) as novel lipid nanocarriers for oral delivery of Decitabine (DCB) using the cold homogenization technique. Box-Behnken design (3(3)) with 17 experimental runs was used to achieve optimal formulations. The optimized batch was characterized by combining particle size distribution analysis, Z-potential, TEM, EE, DL, and DLS measurements, with rheological in-vitro drug release, accelerated stability, and ex-vivo gut permeation studies. The optimized batch revealed SLNs with spherical morphology with TEM-determined particle size of 136.6 +/- 2.35 nm. Z-potential and %EE were found to be -31.34 +/- 0.67 mV and 58.89% +/- 0.78, respectively. The in-vitro release study showed burst release at the initial stage, followed by sustained release over the subsequent 24 hrs in the intestinal medium. Thus, obtained data were further analyzed using release kinetic models, which revealed Higuchi matrix as the best fit model. The ex-vivo gut permeation study proved that the SLNs prepared by using lipid and surfactants allowed a nearly 4-fold increment in the permeation of the drug present in the formulation from the intestine, as compared to plain drug solution. Moreover, SLNs prepared with solid lipid and surfactants held high potential for entrapping DCB, showing better prospects for the oral delivery of DCB.