Studies On Biopolymer Based Nanoparticles For Delivery Of Lithium

Abstract

This work was initiated with a goal to overcome the side effects of lithium for mood disorders. A nanoencapsulant based delivery strategy was formulated based lithium encapsulated in chitosan nanoparticles (CL), lithium encapsulated in gelatin nanoparticles (GL), lithium encapsulated in alginate nanoparticles (AL) and lithium encapsulated in chitosan alginate nanoparticles (CAL). From the zeta potential, size, and percentage of lithium encapsulated, all the nanocarriers were comparable. From XRD, HRSEM and other studies it was postulated that the lithium binds to the biopolymers through ionic linkages or non-specific interactions. In vitro studies using PC 12 cells and DAPI staining technique indicated a better cell differentiation when chitosan nanocarriers were employed. A loading of 7 mg lithium per 20 mg chitosan was optimized. For active targeting of the drug lactoferrin was conjugated to the chitosan nanocarrier (CLL) and the conjugated demonstrated through FTIR measurements. Lactoferrin also helped in the slower release of lithium at physiological pH condition. Through the studies an increased uptake of lithium through endocytosis and receptor mediated endocytic pathway has been suggested. In vivo studies employing mice models and manic condition being induced by vanoxerine clearly demonstrated the advantage of lithium loaded chitosan based nanocarrier delivery systems, which was proved through ECG changes, serum urea and creatine levels, oxidant stress marker parameters, and histopathological studies. The fluorescent tagged nanoparticles clearly demonstrated the advantage of lactoferrin based targeting. In essence, this study demonstrates an alternative route to lithium-based treatment of manic disorders by employing lactoferrin conjugated chitosan nanoparticles as carriers for lithium. This study draws significance in the advantage of nanocarriers to overcome the side effects of several conventional drugs. newline Keywords: Nanotechnology; Nanocarriers; Blood Brain Barrier; Biopolymer; Chitosan nanoparticles; Lithium; Mood disorder; Drug delivery; Targeted drug delivery. newline newline