Balancing loading, cellular uptake, and toxicity of gelatin-pluronic nanocomposite for drug delivery: Influence of HLB of pluronic.

Abstract

In this study, pluronic stabilized gelatin nanocomposite of varying hydrophilic-lipophilic balance (HLB) were synthesized to study the effect of surface hydrophobicity on their cellular uptake and in turn the delivery of a model hydrophobic bioactive compound, curcumin (CUR). Notably, the variation in HLB from 22 to 8 did not cause much change in morphology (~spherical) and surface charge (~ -6.5mV) while marginally reducing the size of nanocomposite from 165 ± 097 nm to 134 ± 074 nm. On contrary, nanocomposites exhibited a very significant increase in their numbers, hydrophobicity as well as CUR loading with decreasing HLB values (22-8) of pluronic. Further, the cellular uptake of CUR through pluronic-gelatin nanocomposites was studied in human lung carcinoma (A549) cells. The results indicated that cellular uptake of CUR through nanocomposites followed the order HLB 22 > HLB 18 > HLB 15 > HLB 8. This was also reflected in terms of the decrease in cytotoxicity of CUR through nanocomposite of HLB 8 as compared to that of HLB 22. Interestingly, bare nanocomposite of HLB 8 showed significantly higher cytotoxicity as compared to that of HLB 22. Together these results suggested that although higher hydrophobicity of the gelatin-pluronic nanocomposite facilitated higher entrapment of CUR, the carrier per se became toxic due to its hydrophobic interaction with lipid bilayer of plasma membrane. Thus, HLB parameter is very important in designing hybrid nanocomposite systems involving protein and pluronic to ensure both bio-compatibility of the carrier and the optimum cellular delivery of the pay load.