Background: A major problem associated with prostate cancer treatment is drug resistance leading to prostate cancer metastasis. Prostate cancer-targeted drug delivery system is one way to address this problem. Traditional drug delivery systems face many challenges, such as inability to control the release rate, inaccurate targeting, susceptibility to the microenvironment, and poor stability of the drug. Hence, there is a need to formulate a drug delivery system and functionalize the surface of delivery system for a better control of drug release.
Targeted drug delivery of nanoparticles decorated with site-specific recognition ligands is of considerable interest to minimize cytotoxicity of chemotherapeutics in the normal cells. This study was designed to measure drug release of SC-514-PLGA nanoparticles and conjugate SC-514 polylactic-co-glycolic acid (PLGA) nanoparticles loaded with NF-KB antibody and fats. This study explored new methods to quantify the SC-514 drug released from SC-514-PLGA nanoparticles. The anti-proliferative effects of the SC-514 drug released by the nanoparticle treatments were investigated in PC-3 cells and cord blood cells. MDR expression in PC-3 cells was investigated after treatment with free SC-514 and SC-514 from SC-514-PLGA nanoparticles.
Methods: SC-514 drug release was studied under in vitro conditions in phosphate buffer solution (PBS) at a pH of 7.4, using dialysis method. Liquid chromatography–mass spectrometry (LC-MS) was utilized as the standard method to quantify SC-514 drug released. Furthermore, other experimental methods utilized to quantify SC-514 drug released included: colony assay, wound healing assay, and transwell migration and invasion assays. MTT calorimetric assay was utilized to investigate the impact of the nanoparticle formulations (SC-514-PLGA, SC-514-PLGA-NF-KB, SC-514-PLGA-Fat) on PC-3 cells and cord blood cells. In addition, in vitro cellular uptake of fluorescent nanoparticle formulations in PC-3 and cord blood cells were examined with confocal fluorescence microscope.
Results: The ligand conjugated nanoparticles showed considerable reduction of tumor growth and toxicity (side-effect of the drug treatment in prostate cancer) of SC-514 drug in prostate cancer treatment. Our results demonstrated that prepared drug delivery system possesses a much lower toxicity, better prostate cancer controlled-release behaviors and confers higher solubility to SC-514 than free SC-514. SC-514 released from SC-514-PLGA, PLGA-SC-514-NF-KB, and PLGA-SC-514-Fat significantly inhibited tumor growth when compared to free SC-514. A more significant reduction of cell viability was recorded in PC-3 cells by all treatments (Free SC-514, SC-514-PLGA, and SC-514-PLGA-NF-KB) compared to cord blood cells, except for SC-514-PLGA-Fat nanoparticle formulation. SC-514 drug from SC-514-PLGA nanoparticles reduced the expression of MDR proteins than free SC-514.
Conclusion: Encapsulation of SC-514 with PLGA polymer increased the anti-cancer therapeutic effects of SC-514 drug. Burst release from SC-514-PLGA nanoparticles can be controlled by functionalization. New methods of quantifying drug release maybe as effective as the standard methods of drug quantification, such as LC/MS method.