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

S M Jusu,O S Odusanya,J D Obayemi,V Uzonwanne,C C Nwazojie,A A Salifu,W O Soboyejo

doi:10.1038/s41598-020-71129-0

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.

Highlights

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
The hydrodynamic diameter obtained from the Dynamic Light Scattering (DLS) (Table 1) were greater than the mean diameter obtained from the Scanning Electron Microscopy (SEM) (Fig. 1F)
This could be attributed to the polyethylene glycol (PEG) being soluble in the DLS medium leading to a swollen structure with high water content[55]

Summary

Introduction

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. The positive values obtained for the change in enthalpy (ΔH) confirm that the drug release process (from all of the PLGA-PEG microspheres formulations containing PGS, PGS-LHRH or PTX-LHRH respectively) was endothermic. The Trypan blue dye (TBD) cell count was used to confirm the effects of the drug-loaded PLGA-PEG microsphere treatment on MDA-MB-231 cell viability.

Results

Conclusion