Dual Drug Delivery Using Lactic Acid Conjugated SLN for Effective Management of Neurocysticercosis.

Abstract

The debut study was aimed to develop Lactic acid (LA)-conjugated solid lipid nanoparticles (SLN-LA) bearing albendazole (ALB) and prednisolone (PRD) for effective management of neurocysticercosis (NCC). LA was coupled to SLN by post-insertion technique. SLNs were characterized for particle size and size distribution, shape, and percent drug entrapment efficiency. In vitro drug release kinetics, fluorescence study and in vitro transendothelial transport, hematological studies and pharmacokinetic studies were carried out to predict the fullest drug delivery potential. Spherical SLNs (~100 nm) with good drug entrapments (~64 and ~78% for ALB and PRD, respectively) showed in vitro initial fast release (i.e., 20-40% drugs release in 4 h) followed by sustained release for more than 48 h. Fluorescence study and in vitro transendothelial transport depicted selective brain uptake of SLN-LA compared to SLN attributed to carrier mediated transport via monocarboxylic acid transporters (MCT - 1/2/3). Pharmacokinetic parameters such as AUC0-t and AUMC0-t and Cllast showed good drugs withholding capacity of SLNs. Organ distribution studies reflected high accumulation of drugs (ALB, 7.6 ± 0.31%; PRD, 5.21 ± 0.24%) in the brain after 24 h in case of SLN-LA as compared to plain drugs solution. SLN-LA in hematological studies revealed insignificant toxicity to blood cells. The overall study paved the potential advances in brain targeting with synergistic acting drugs for effective management of NCC.