Triple-negative breast cancer (TNBC) is more aggressive and difficult to treat using conventional bulk chemotherapy that is often associated with increased toxicity and side effects. In this study, we encapsulated targeted drugs [A bacteria-synthesized anticancer drug (prodigiosin) and paclitaxel] using single solvent evaporation technique with a blend of FDA-approved poly lactic-co-glycolic acid-polyethylene glycol (PLGA_PEG) polymer microspheres. These drugs were functionalized with Luteinizing Hormone-Releasing hormone (LHRH) ligands whose receptors are shown to overexpressed on surfaces of TNBC. The physicochemical, structural, morphological and thermal properties of the drug-loaded microspheres were then characterized using Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), Nuclear Magnetic Resonance Spectroscopy (NMR), Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). Results obtained from in vitro kinetics drug release at human body temperature (37 °C) and hyperthermic temperatures (41 and 44 °C) reveal a non-Fickian sustained drug release that is well-characterized by Korsmeyer-Peppas model with thermodynamically non-spontaneous release of drug. Clearly, the in vitro and in vivo drug release from conjugated drug-loaded microspheres (PLGA-PEG_PGS-LHRH, PLGA-PEG_PTX-LHRH) is shown to result in greater reductions of cell/tissue viability in the treatment of TNBC. The in vivo animal studies also showed that all the drug-loaded PLGA-PEG microspheres for the localized and targeted treatment of TNBC did not caused any noticeable toxicity and thus significantly extended the survival of the treated mice post tumor resection. The implications of this work are discussed for developing targeted drug systems to treat and prevent local recurred triple negative breast tumors after surgical resection.

This paper presents the anomalous release kinetics of a cancer drug (prodigiosin) frompoly-n-isopropyl-acrylamide(P(NIPA))-based gels. The release exponents, n, which correspond to the drug release mechanisms, were found to be between 0.41 and 1.40. This is within a range that include Fickian case I (n = 0.45) and non-Fickian diffusion (case II) (n > 0.45) for cylindrical drug-loaded structures. The results, however, suggest that the release exponents, n, correspond mostly to anomalous case II and super case II transport mechanics with sigmoidal characteristics. The drug release kinetics of the P(NIPA)-based hydrogels are well described by bi-dose functions. The observed drug release behavour is related to the porosity of the hydrogels, which can be controlled by cross-linking and copolymerization with acrylamide, which also improves the hydrophilicity of the gels. The paper also presents the effects of cancer drug release on cell survival (%), as well as the cell metabolic activities of treated cells and non-treated cells. The implications of the results are discussed for the development of implantable thermosensitive gels for the controlled release of drugs for localized cancer treatment.