The aim of the present investigation was to fabricate and evaluate solid lipid nanoparticles (SLNs) of asenapine maleate (AM) to improve its oral bioavailability (BA). AM-SLNs were prepared by high speed homogenization followed by ultrasonication technique. The resultant SLNs exhibited particle size, zeta potential and entrapment efficiency of 114.3 ± 3.5 nm, -12.9 ± 3.8 mV, and 84.10% ± 2.90% respectively. In vitro release study of AM-SLNs showed 9.23% ± 2.72% and 92.09% ± 3.40% release of AM in pH 1.2 medium and phosphate buffer pH 6.8, respectively, indicating higher potential of lymphatic uptake. Cell viability study using Caco-2 cell line indicated non-toxicity of the carriers and drug. The uptake of AM-SLNs across Caco-2 cell line was time and energy dependent exhibiting clathrin-claveole mediated endocytosis transport. Cellular uptake of Coumarin loaded SLNs was effectively increased as compared to the dye solution. The pharmacokinetic results in rats showed 50.19-fold improvement in BA of AM after fabrication of SLNs. Collectively, all these findings demonstrated effectiveness of SLNs to improve therapeutic efficacy of AM in the treatment of schizophrenia.
Keywords: Asenapine maleate; Caco-2 cell line; bioavailability; lymphatic transport; oral absorption mechanism; solid lipid nanoparticles.