Cellular uptake and cytotoxicity studies of pH-responsive polymeric nanoparticles fabricated by dispersion polymerization

OBJECTIVE: A strategy in site-specific drug delivery is the use of pH-gradients that exist in diseased conditions such as cancer for the release of loaded drug(s) in the biophase. The objective of this work is to synthesize pH-responsive docetaxel-loaded nanoparticles with a bisacrylate acetal crosslinker, which can get internalized into cells, and which will be equivalent to or more cytotoxic than the free drug against cancer cells. METHODS: pH-responsive nanoparticles were synthesized by a dispersion polymerization technique. The nanoparticles were characterized for physicochemical properties. Cytotoxicity studies of the nanoparticles were performed on PC3 and LNCaP prostate cancer cell lines using a cell viability assay. Cellular uptake studies were performed using a confocal laser scanning microscope. RESULTS: Smooth spherical nanoparticles were formed. In-vitro drug release was faster at pH 5.0 than pH 7.4, which confirmed the pH-responsiveness of the nanoparticles. Cytotoxicity studies showed that the nanoparticles were more effective at the same molar amount than the free drug against cancer cells. Both dose exposure and incubation time affected the cytotoxicity of prostate cancer cells. Furthermore, LNCaP cells appeared to be the more sensitive to docetaxel than PC3 cells. The cellular uptake studies clearly showed the presence of discrete nanoparticles within the cells in as little as 2 hours. CONCLUSION: pH-sensitive nanoparticles were developed; they degraded quickly in the mildly acidic environments similar to those found in endosomes and lysosomes of tumor tissues. These novel pH-sensitive nanoparticles would offer several advantages over conventional drug therapies.