Brain delivery and systemic effect of cationic albumin conjugated PLGA nanoparticles

Cationic bovine serum albumin (CBSA)-conjugated poly(ethylene glycol)–poly(d,l-lactide-co-glycolide) (PEG–PLGA) nanoparticle (CBSA–NP) is an innovative protein and genes carrier for brain delivery. In the present study, single factor and orthogonal experiments have been carried out to optimize the formulation of preparing CBSA. Effects of varying formulation parameters on NP size were also determined. Quantitative and qualitative analyses of CBSA–NP and NP uptake by brain capillary endothelial cells were evaluated using 6-coumarin as the fluorescent probe. Uptake process was demonstrated to be dependent on the concentration of NPs, incubation time, and energy. Biodistribution indicated that our optimized CBSA–NP was efficiently taken up by the brain tissue, but did not lead to a general enhanced uptake into all tissues. Splenic accumulation of CBSA–NP was prominently decreased when compared with results from our previous studies. The optimized CBSA pI value was 8.9 and the achieved CBSA–NP obtained a concentration that was 2.31-fold compared with NP. Moreover, the splenic AUC of CBSA–NP was only 0.29-fold compared with that of NP. These results indicated that CBSA–NP was an ideal carrier for targeted brain delivery.