RESUMO
Asenapine maleate (ASPM) is an antipsychotic drug prescribed for the treatment of schizophrenia and bipolar disorder. ASPM possesses low oral bioavailability due to extensive hepatic metabolism. Therefore, RGD peptide conjugated liposomes loaded with ASPM were prepared to target Peyer's patches in the intestine which in-turn get access into intestinal lymphatic system thereby increasing the oral bioavailability of the drug. Liposomes were evaluated for size, zeta potential, differential scanning calorimetry (DSC), FTIR spectroscopy, X-ray diffraction (XRD), shape and morphology, in vitro drug release, cell line studies, everted intestinal uptake, pharmacodynamics, pharmacokinetics, tissue distribution, targetability and stability studies. In vitro drug release study showed the sustained release of drug from the formulations. Optimized liposomes (size <110 nm) showed greater permeability across the Caco2 + Raji B co-culture model in vitro and everted rat ileum ex vivo. Liposomes showed increase in bioavailability and high efficacy in reducing the L-DOPA-carbidopa induced locomotor count compared to plain drug. Liposomes also showed high concentration of drug in the brain after their oral administration. Imaging studies showed that RGD peptide conjugated liposomes were successful in targeting the Peyer's patches, both in vivo and ex vivo. The study successfully demonstrated the improved pharmacokinetics and efficacy profile of ASPM by using a ligand conjugated targeted liposomal system.