Nanoparticles made of multiblock copolymer of lactic acid and ethylene glycol containing periodic side–chain carboxyl groups for oral delivery of cyclosporine A

The purpose of this study was to evaluate the potential of new carboxylated multiblock copolymer of lactic acid and ethylene glycol (EL14) for nanoparticle formation and their ability to deliver high molecular weight hydrophobic drug-Cyclosporine A (CsA). CsA loaded EL14 nanoparticles (NPs) were compared to traditional PLGA NPs, both prepared by emulsion-diffusion-evaporation process. The increase in drug payload from 10 to 30% for EL14 NPs showed no difference in particle size, however the entrapment efficiency tends to decrease from 50 to 43%, on the other hand the more hydrophobic PLGA showed an increasing trend in entrapment efficiency from 20 to 62% with increasing particle size. Over 90% of CsA was released in vitro from both the nanoparticulates; however the release was much slower in case of more hydrophobic PLGA. On in vivo evaluation in rats, the nanoparticles made of EL14 showed a higher Cmax, a faster Tmax and enhanced tissue levels to that of PLGA, that are crucial for CsA activity and toxicity, however the overall bioavailability of the nanoparticulates were similar and higher than Neoral®. Together these data demonstrate the feasibility of nanoparticles made of low molecular weight, hydrophilic polymer EL14 for efficient delivery of CsA