LAUSR

Gelatin based nanocarriers have major limitation of shorter circulation half-life (t1/2). Present study addressed this issue by conjugating gelatin with folate followed by nanoprecipitation in presence of polysorbate 80 forming folate attached gelatin nanoparticles (GNP-F). The folic acid was conjugated with gelatin through the formation of amide linkage with a maximum conjugation yield of ∼69 %. Cryo-SEM analysis indicated that unconjugated gelatin nanoparticles (GNP) and GNP-F were spherical of nearly identical size of ∼200 nm. The irinotecan (IRI)-loading efficiency estimated for IRI-GNP and IRI-GNP-F was 6.6 ± 0.42 % and 11.2 ± 0.73 % respectively and both formulations showed faster release of IRI at acidic pH (∼5) than at physiological pH (∼7). Further IRI-GNP-F demonstrated significantly higher cytotoxicity in folate receptor (FR)-positive HeLa cells than the unconjugated IRI-GNP nanoparticles confirming active targeting. Subsequently the antitumor activity of above formulations in FR-positive fibrosarcoma (syngeneic) tumor-bearing mice followed the order of IRI-GNP-F>IRI-GNP>free IRI. The pharmacokinetic evaluation of IRI-GNP and IRI-GNP-F revealed that encapsulation of IRI within GNP without folate improved its plasma maximum concentration (Cmax). However, folate conjugation of GNP remarkably improved the t1/2 of IRI. Taken together, folate as a targeting ligand modulates the pharmacokinetic property of IRI loaded GNP to favor active verses passive targeting.