A representative
poly(beta-amino ester) (PbAE) with biodegradable and pH-sensitive properties was used to formulate a nanoparticle-based
dosage form for
tumor-targeted
paclitaxel delivery. The
polymer undergoes rapid dissolution when the pH of the medium is less than 6.5 and hence is expected to release its contents at once within the acidic tumor microenvironment and endo/lysosome compartments of cells. PbAE nanoparticles were prepared by
solvent displacement method and characterized for particle size, charge, and surface morphology.
Pluronic F-108, a triblock copolymer of poly(
ethylene oxide) (PEO) and
poly(propylene oxide) (PPO), was blended with PbAE to induce surface modification of the nanoparticles. In vitro cellular uptake of tritiated [(3)H]-
paclitaxel in
solution form and as a nanoparticulate formulation was studied in MDA-MB-231 human breast
adenocarcinoma cells grown in 12-well plates. We also examined the intracellular degradation pattern of the formulations within the cells by estimating the drug release profile. Cytotoxicity assay was performed on the formulations at different doses and time intervals. Nanoparticles prepared from
poly(epsilon-caprolactone) (PCL) that do not display pH-sensitive release behavior were used as control. Spherical nanoparticles having positive zeta potential ( approximately 40 mV) were obtained in the size range of 150-200 nm with PbAE. The PEO chains of the
Pluronic were well-anchored within the nanomatrix as determined by electron spectroscopy for chemical analysis (ESCA). The intracellular accumulation of
paclitaxel within
tumor cells was significantly higher when administered in the nanoparticle formulations as compared to aqueous
solution. Qualitative fluorescent microscopy confirmed the rapid release of the payload into the cytosol in the case of PbAE nanoparticles, while the integrity of the PCL nanoparticles remained intact. The cytotoxicity assay results showed significantly higher tumoricidal activity of
paclitaxel when administered in the nanoparticle formulations. The cell-kill effect was maximal for
paclitaxel-loaded PbAE nanoparticles when normalized with respect to intracellular
drug concentrations. Thus, PEO-modified PbAE nanoparticles show tremendous potential as novel carriers of
cytotoxic agents for achieving improved
drug disposition and enhanced efficacy.