Drug-encapsulated blend of PLGA-PEG microspheres: in vitro and in vivo study of the effects of localized/targeted drug delivery on the treatment of triple-negative breast cancer

Abstract

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.

In vitro studies of Annona muricata L. extract‐loaded electrospun scaffolds for localized treatment of breast cancer

“…The effect of the surfactant observed in this study is consistent with the findings of our prior work on the encapsulation of prodigiosin in electrospun fibers. 16 Although the proportion of the encapsulated prodigiosin (PG) released from the pluronic F127-containing fibers was similar (i.e., 50%) under the same sink conditions at physiological temperature and pH, a lower percentage of prodigiosin (PG) was released from the non-pluronic F127 fibers than in this study (80% vs. 90%). This suggests that the surfactant exerts similar stabilizing effects on the fibers (PLGA/Ge) and drugs (AME and PG) to prolong their release, whereas, in the absence of the surfactant, the AME extract and PG drug exhibit different diffusion rates out of the fibers.…”

“…13 Prior works have also explored the development of sustainedrelease drug delivery systems in an attempt to maintain and localize the anticancer drug concentrations at desirable doses over longer durations than bulk systemic chemotherapy to maximize therapeutic effect. [14][15][16] A few researchers have reported the successful loading of AME extracts into drug delivery carriers to potentiate their cytotoxic effects through their sustained release to the target cells. [17][18][19] For instance, Aruan et al 17 incorporated AME leaf extracts into electrospun polyvinyl alcohol nanofiber scaffolds and demonstrated the cytotoxic effects of the released extracts on the growth of Staphylococcus aureus.…”

PLGA Nanoparticle-Based Formulations to Cross the Blood–Brain Barrier for Drug Delivery: From R&D to cGMP

“…To overcome its short half-life, PLGA is combined with polyethylene glycol (PEG) to form PLGA-PEG copolymer NPs [63][64][65]. The PLGA-PEG copolymer is widely used in pharmaceutical products and devices.…”

An Insulin-like Growth Factor-1 Conjugated Bombyx mori Silk Fibroin Film for Diabetic Wound Healing: Fabrication, Physicochemical Property Characterization, and Dosage Optimization In Vitro and In Vivo

“…This study employed FTIR to characterize the chemical bonds/functional groups on SF-film that were relevant to the physicochemical properties and drug-loading capabilities of the film [43]. This study did not observe significant wavenumber shifts in the SF-…”