Recuperating Biopharmaceutical Aspects of Amphotericin B and Paromomycin Using a Chitosan Functionalized Nanocarrier via Oral Route for Enhanced Anti-leishmanial Activity
Shabi Parvez, Ganesh Yadagiri, Archana Karole, Om Prakash Singh, Anurag Verma, Shyam Sundar, Shyam Lal Mudavath
Abstract
The design and development of new pharmaceutical formulations for the existing anti-leishmanial is a new strategic alternate to improve efficacy and safety rather than new drug discovery. Herein hybrid solid lipid nanoparticles (SLN) have been engineered to direct the oral delivery of two anti-leishmanial drugs amphotericin B (AmB) and paromomycin (PM). The combinatorial nanocarriers consist of conventional SLN, antileishmanial drugs (AmB and PM) which have been functionalized with chitosan (Cs) grafted onto the external surface. The Cs-SLN have mean particle size of 373.9 ±1.41 nm, polydispersity index (PDI) of 0.342±0.02 and the entrapment efficiency for AmB and PM was found to be 95.20±3.19 % and 89.45± 6.86 % respectively. Characterization of SLN was performed by scanning electron microscopy and transmission electron microscopy. Complete internalization of the formulation was observed in Caco-2 cells. Cs-SLN have shown a controlled and slow drug release profile over a period of 72 hrs and was stable at gastrointestinal fluids, confirmed by in vitro simulated gastro-intestinal fluid study. Cs coating enhanced the mucoadhesive property of Cs-SLN. The in-vitro anti-leishmanial activity of Cs-SLN (1µg/ml) has shown a maximum percentage of inhibition (92.35% and 89% respectively) on intra-cellular amastigote growth of L. donovani.