Passive internalization and active extrusion determines PLGA-nanoparticle concentration in cancer cell lines

Background:Poly(lactic-co-glycolic) acid nanoparticle (PLGA-NP) trafficking across cell membranes was investigated to confirm preliminary results that contradicted existing studies.Materials & methods:Uptake and retention of PLGA-NPs at 37 and 4 degrees C in the presence and absence of metabolic inhibitors in various cell lines was estimated.Results:Pulse experiments with metabolic inhibitors and culturing at 4 degrees C demonstrated the predominantly passive nature of PLGA-NP uptake. Chase experiments with metabolic inhibitors indicated the role of active exocytosis in the extrusion of these NPs. PLGA-NPs with ionic or nonionic hydrophilic coats with highly positive or negative zeta-potential also showed similar results.Conclusion:Our study opens up the possibility of modulation of active exocytosis to increase intracellular retention of NPs for an extended period of drug delivery.