Characterization of the self assembly of methoxy poly(ethylene oxide)-block-poly(α-benzyl carboxylate-ε-caprolactone) for the solubilization and in vivo delivery of valspodar

摘要

The aim of this study was to characterize the nanostructures formed from assembly of poly (ethylene oxide)-b-poly(α-benzyl carboxylate ε-caprolactone) (PEO-b-PBCL) in water, determine the effect of weight fraction of the hydrophilic block(f EO) on their morphology, and to investigate their potential for solubilization and delivery of P-glycoprotein (P-gp) inhibitor, valspodar. Three PEO-b-PBCL block copolymers having f EO ranging from 0.18-0.40 were synthesized. Assembly of PEO-b-PBCL was triggered through a co-solvent evaporation method. The average critical aggregation concentration (CAC) for PEO 114-b-PBCL 30, PEO 114-b-PBCL 60, and PEO 114-b-PBCL 95 was found to be 62, 41, and 23 nM, respectively. A lower rigidity of the hydrophobic domain in nanostructures formed from the assembly of PEO 114-b-PBCL 60 and PEO 114-b-PBCL 95 in comparison to PEO 114-b-PBCL 30 was observed. The morphology of the assembled structures was characterized by transmission electron microscopy (TEM). The TEM images of PEO 114-b-PBCL 30 (f EO = 0.40) showed the formation of spherical micelles with high polydispersity, whereas the assembly of PEO 114-b-PBCL 60 (f EO = 0.25) and PEO 114-b-PBCL 95 (f EO = 0.18) resulted in a mixed population of spherical micelles and vesicles. Valspodar achieved high loading in all the three PEO-b-PBCL nanocarriers reaching aqueous solubility of nearly 2 mg/mL. The morphology of PEO-b-PBCL carrier did not seem to influence the pharmacokinetics of the encapsulated valspodar in rats following intravenous administration. In conclusion, the results show a potential for PEO-b-PBCL nanocarriers as efficient solubilizing agents for delivery of valspodar.