Abstract
A major problem associated with prostate cancer treatment is the development of drug resistance. The development of drug resistance often leads to prostate cancer metastasis and prostate cancer-targeted drug delivery systems can be utilized to address this problem. Traditional drug delivery systems have many challenges, including the inability to control the drug release rate, target site inaccuracy, susceptibility to the microenvironment, poor drug solubility, and cytotoxicity of chemotherapeutics to non-malignant cells. As a result, there is an urgent need to formulate and functionalize a drug delivery system that better controls drug release. This study was designed to quantify the release of SC-514 from SC-514 Polylactic-Co-Glycolic Acid (PLGA) nanoparticles and conjugate SC-514-PLGA coated nanoparticles with the NF- κβ antibody, as well as fats. This study further explored new methods to quantify the release of SC-514 drug from the SC-514-PLGA coated nanoparticles after utilizing Liquid Chromatography–Mass Spectrometry (LC-MS) as the standard method to quantify SC-514 drug released. After quantification was completed, cell viability studies indicated that the ligand conjugated nanoparticles demonstrated a considerable ability to reduce tumor growth and SC-514 drug toxicity in the PC-3 cell line. The prepared drug delivery systems also possessed a significantly lower toxicity (P<0.05), bettered controlled-release behaviors in prostate cancer, and increased the solubility of SC-514 in comparison to free SC-514. SC-514 released from SC-514-PLGA, SC-514-PLGA-NF- κβAb, and SC-514-PLGA-Fat nanoparticles, significantly inhibited tumor growth when compared to that of free SC-514. The anti-cancer therapeutic effects of SC-514 were improved through the encapsulation of SC-514 with a PLGA polymer. The functionalized SC-514-PLGA nanoparticles can further control burst release. The new methods utilized in this study for quantifying drug release, may prove to be as effective as the current standard methods, such as LC/MS.
Highlights
Lactic-co-glycolic acid, referred to as Polylactic-Co-Glycolic Acid (PLGA), is one of the most successfully used biodegradable polymers used in controlled drug delivery systems [1,2,3,4]
This study further explored new methods to quantify the release of SC-514 drug from the SC-514-PLGA coated nanoparticles after utilizing Liquid Chromatography–Mass Spectrometry (LC-mass spectrometry (MS)) as the standard method to quantify SC-514 drug released
Our previous study indicated that the methodology of nanoparticle preparation allowed the formation of spherical Nano metric particles, homogeneous and negatively charged particles which are suitable for intravenous administration
Summary
Lactic-co-glycolic acid, referred to as PLGA, is one of the most successfully used biodegradable polymers used in controlled drug delivery systems [1,2,3,4]. Over the past 50 years, the development of biodegradable polymers has represented a revolution in medicine and has led to significant biotechnological advancements for drug delivery, biomaterials, tissue engineering, and medical device development. The development of these biodegradable polymers has been made possible through a unique collaboration between chemists, engineers, biologists, and physicians. One of the major driving forces for the development of polymeric drug delivery platforms has been the necessity of improving cancer therapeutics. The numerous therapeutic advantages of polymeric drug delivery platforms can be attributed to their versatile nature and ability to control drug release [6,7,8]
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