Surface-modified polycaprolactone nanoparticles for the brain-targeted delivery of nevirapine

Abstract

The low-density lipoprotein (LDL) receptors overexpressed in brain capillary endothelial cell (BCEC) membrane were successfully targeted by polysorbate 80 (PS80)-coated polycaprolactone (PCL) nanoparticles for brain delivery of nevirapine (NVP). The nanoparticles prepared by emulsion solvent evaporation technique were evaluated for mean particle size (nm), zeta potential (mV), percentage drug entrapment efficiency (% EE), percentage drug loading (% DL), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), transmission electron microscopy (TEM), in vitro drug release study, stability study and in vivo biodistribution study. The mean particle size (nm) of uncoated nanoparticles, NvPNPs5, and PS80-coated nanoparticles, P80NvPNPs5, were (128.43 ± 4.82) nm and (218.3 ± 7.3) nm, respectively. The SEM and TEM analysis showed small-sized (< 100 nm), spherical-shaped, smooth-surface nanoparticles with less aggregation. The zeta potential (mV) analysis showed stable nanoparticles with values (− 72.1 ± 0.00) mV, NvPNPs5; (− 16.2 ± 0.00) mV, P80NvPNPs5; (− 16.2 ± 0.00) mV, 6CFNvPNPs5; and (− 13.6 ± 0.00) mV, P806CFNvPNPs5. The FT-IR and DSC report indicated drug excipient compatibility. P80NvPNPs5 showed an in vitro drug release for 36 h and its release kinetic was best fitted in Higuchi model (R2 = 0.936). Korsemeyer Peppas model showed an anomalous non-Fickian drug release mechanism as n = 0.767. P80NvPNPs5 released NVP for 24 h in the brain with prolonged blood circulation for 48 h as compared with NvPNPs5 and free drug suspension, (p < 0.05) in in vivo biodistribution study in Swiss Wistar rat. The confocal laser scanning microscopy (CLSM) study showed uniform distribution of P80NvPNPs5 in rat BCECs for 24 h post i.v. administration. The present observation concludes the futuristic scope of P80NvPNPs5 nanoparticles for brain delivery of different antiretroviral drugs as well as other CNS active drugs to treat several CNS disorders.