Development of biocompatible nanogel for sustained drug release by overcoming the blood brain barrier in zebrafish model

Abstract

A potential delivery system has to be fabricated for crossing the blood-brain barrier (BBB) to reach the brain fluid for effective delivery of drugs for any neurological disorders. The present study is aimed for the delivery of donepezil through functionalized PNIPAM nanogel by overcoming the BBB using zebrafish model. We had synthesized the poly N-isopropyl acrylamide nanogels with 20 nm size for sustained drug release. The entrapment of donepezil in the nanogel was quantified as 87.5% by HPLC and its sustained drug release pattern was achieved at 37 °C using Janus green dye release assay. Acetylcholineesterase inhibition assay for the donepezil conjugated nanogel (DCN) has confirmed thermoresponsive drug release by obtaining the donepezil peak at 9.3 min retention time in HPLC. Swim behavior and heart beat rates were found to be biocompatible for the functionalized nanogel DCN in zebrafish. Histological analysis revealed increased pial surface in anterior telenchepalon region of zebrafish brain for the DCN administered fishes. DCN treated embryos exhibited minor developmental deformities above 5 μg/ml and thus confirmed its minimal toxicity and its therapeutic efficiency. This study may shed light on the development of neurospecific nanogel for targeted and sustained drug release to brain by crossing the blood-brain barrier.