Enhanced cellular delivery of idarubicin by surface modification of propyl starch nanoparticles employing pteroic acid conjugated polyvinyl alcohol
2011
Jain, Ratnesh | Dandekar, Prajakta | Loretz, Brigitta | Melero, Ana | Stauner, Thomas | Wenz, Gerhard | Koch, Marcus | Lehr, Claus-Michael
Enhanced intracellular internalization of the anti-cancer active idarubicin (IDA) was achieved through appropriate surface modification of IDA loaded propyl starch nanoparticles. This was conducted by synthesizing pteroic acid modified polyvinyl alcohol (ptPVA) and employing this stabilizer for formulating the said nanoparticles. Pteroic acid attached at the nanoparticles improved the surface protein adsorption of the nanoparticle, a condition which the nanoparticles would largely experience in vitro and in vivo and hence improve their cellular internalization. Spherical, homogenous IDA nanoparticles (214±5nm) with surface modified by ptPVA were formulated using the solvent emulsification–diffusion technique. The encapsulation efficiency and drug loading amounted around 85%. In vitro release studies indicated a controlled release of IDA. Safety and efficacy of the nanoparticles was confirmed by suitable cellular cytotoxicity assays. Protein binding studies indicated a higher adsorption of the model protein on nanoparticles formulated with ptPVA as compared to PVA. Cellular uptake studies by confocal laser scanning microscopy revealed a higher cellular uptake of ptPVA stabilized nanoparticles thus confirming the proposed hypothesis of higher protein adsorption being responsible for higher cellular internalization.
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