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
Z, Binkhathlan . 2012
The aim of this study was to characterize the nanostructures formed from assembly of poly(ethylene oxide)-bpoly( α-benzyl carboxylate ε-caprolactone) (PEO-b-PBCL) in water, determine the effect of weight fraction of the hydrophilic block( fEO) 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 fEO 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 PEO114-b-PBCL30, PEO114-b-PBCL60, and PEO114-b-PBCL95 was found to be 62, 41, and 23 nM, respectively. A lower rigidity of the hydrophobic domain in nanostructures formed from the assembly of PEO114-b- PBCL60 and PEO114-b-PBCL95 in comparison to PEO114-b-PBCL30 was observed. The morphology of the assembled structures was characterized by transmission electron microscopy (TEM). The TEM images of PEO114-b-PBCL30 (fEO = 0.40) showed the formation of spherical micelles with high polydispersity, whereas the assembly of PEO114-b-PBCL60 (fEO = 0.25) and PEO114-b-PBCL95 (fEO = 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.
A liquid chromatography-mass spectrometry (LC/MS) assay method was developed for the quantification of PSC 833 in rat plasma, using amiodarone as internal standard (IS).
Valspodar is a P-glycoprotein inhibitor widely used in preclinical and clinical studies for overcoming multidrug resistance. Despite this, the pharmacokinetics of valspodar in rat, a commonly used…
The aim of this study was to assess the potential of polymeric micelles to solubilize valspodar and modify its pharmacokinetics following intravenous and oral administration in rat.