Investigation on design of stable etoposide-loaded PEG-PCL micelles: effect of molecular weight of PEG-PCL diblock copolymer on the in vitro and in vivo performance of micelles.

In the present study, six different molecular weight diblock copolymer of methoxy poly (ethylene glycol)-b-poly (ε-caprolactone) (MPEG-PCL) were synthesized and characterized and was used for fabrication of etoposide-loaded micelles by nanoprecipitation technique. The particle size and percentage drug entrapment of prepared micelles were found to be dependent on the molecular weight of PCL block and drug to polymer ratio. The maximum drug loading of 5.32% was found in micellar formulation MPEG5000-PCL10000, while MPEG2000-PCL2000 exhibited 2.73% of maximum drug loading. A variation in the fixed aqueous layer thickness and PEG surface density of micellar formulations was attributed to difference in MPEG molecular weight and interaction of PEG and PCL block of copolymer. The MPEG2000-PCL2000 micelles demonstrated poor in vitro stability among other micellar formulations, due to its interaction with bovine serum albumin and immediate release of drug from micelles. Furthermore, plain etoposide and MPEG2000-PCL2000 micelles exhibited greater extent of hemolysis, due to presence of surfactants and faster release of drug from micelles, respectively. The biodistribution studies carried out on Ehrlich ascites tumor-bearing Balb/C mice confirmed higher accumulation of etoposide-loaded micellar formulation at tumor site compared to plain etoposide due to enhanced permeability and retention effect.

PLGA nanoparticles loaded with etoposide and quercetin dihydrate individually: in vitro cell line study to ensure advantage of combination therapy.

PLGA nanoparticles, separately loaded with etoposide (ETN) and quercetin dihydrate (QDN), were prepared by adapting the solvent diffusion (nanoprecipitation) technique. The effect of formulation variables such as amount of polymer, theoretical drug loading, surfactant concentration, and aqueous and organic phase volumes on particle size and entrapment efficiency, were systematically studied. The optimal formulations obtained were of submicron size (153.4 ± 4.2 nm for ETN and 148.6 ± 1.6 nm for QDN) and with low polydispersity indices (0.058 ± 0.02 for ETN and 0.088 ± 0.03 for QDN). The entrapment efficiencies were found as 63.88 ± 1.5 % and 41.36 ± 3.4 % for ETN and QDN, respectively. The characterization of ETN and QDN was done by measuring the zeta potential, TEM, and DSC analysis. The comparison was made in respect of in vitro cytotoxicity assay using cancer cell line A549 (human lung adenocarcinoma epithelial cell line). The results revealed significant increase in cytotoxicity in nanoparticle formulations than their respective free drug. The comparison was also made with respect to cytotoxic activity of individual drug and combination of drugs in the form of free drugs as well as nanoparticles. The combination treatment in the form of nanoparticles is found to produce best results among the treatments used in cytotoxicity studies.