PLGA-CS-PEG Microparticles for Controlled Drug Delivery in the Treatment of Triple Negative Breast Cancer Cells

Sandra Musu Jusu,Winnston Oluwole Soboyejo,Olushola Segun Odusanya,Ali Azeko Salifu,Chukwudalu Clare Nwazojie,John David Obayemi,Vanessa Obiageli Uzonwanne

doi:10.3390/app11157112

Sandra Musu Jusu, Winnston Oluwole Soboyejo + Show 5 more

Open Access

https://doi.org/10.3390/app11157112

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Abstract

In this study, we explore the development of controlled PLGA-CS-PEG microspheres, which are used to encapsulate model anticancer drugs (prodigiosin (PGS) or paclitaxel (PTX)) for controlled breast cancer treatment. The PLGA microspheres are blended with hydrophilic polymers (chitosan and polyethylene glycol) in the presence of polyvinyl alcohol (PVA) that were synthesized via a water-oil-water (W/O/W) solvent evaporation technique. Chitosan (CS) and polyethylene glycol (PEG) were used as surface-modifying additives to improve the biocompatibility and reduce the adsorption of plasma proteins onto the microsphere surfaces. These PLGA-CS-PEG microspheres are loaded with varying concentrations (5 and 8 mg/mL) of PGS or PTX, respectively. Scanning electron microscopy (SEM) revealed the morphological properties while Fourier transform infrared spectroscopy (FTIR) was used to elucidate the functional groups of drug-loaded PLGA-CS-PEG microparticles. A thirty-day, in vitro, encapsulated drug (PGS or PTX) release was carried out at 37 °C, which corresponds to human body temperature, and at 41 °C and 44 °C, which correspond to hyperthermic temperatures. The thermodynamics and kinetics of in vitro drug release were also elucidated using a combination of mathematical models and the experimental results. The exponents of the Korsmeyer–Peppas model showed that the kinetics of drug release was well characterized by anomalous non-Fickian drug release. Endothermic and nonspontaneous processes are also associated with the thermodynamics of drug release. Finally, the controlled in vitro release of cancer drugs (PGS and PTX) is shown to decrease the viability of MDA-MB-231 cells. The implications of the results are discussed for the development of drug-encapsulated PLGA-CS-PEG microparticles for the controlled release of cancer drugs in treatment of triple negative breast cancer.

Highlights

Further in vivo work is needed to investigate the possible outcome of extended cancer drug release from the microparticles that were produced in this study, the current work does show that the combined use of polyethylene glycol (PEG) and CS polymer can be used to control the thermodynamics and the kinetics of the controlled release characteristics (Figure 4a–d and Tables 4 and 5)
The kinetics of drug release from both types of microspheres are well characterized by the Korsmeyer–Peppas model, with release exponents n within the range of 0.45 < n < 0.89
The in vitro drug release profiles obtained in this study exhibit a biphasic-controlled release of anticancer drugs from drug-loaded PLGACS-PEG microspheres with >50% drug released at day 30

Summary

Introduction

Kinetics; drug delivery; prodigiosin; paclitaxel and Cancer is the second leading cause of death globally [1,2] It was the cause of death for an estimated 9.6 million people in 2018 [1,2]. Cancer deaths will continue to rise, with 13 million people projected to die of cancer in 2030 At this rate, cancer may surpass cardiovascular disease as the leading cause of death, globally [2]. Current treatment modalities include radiotherapy, chemotherapy, hormonal therapy, and surgical removal [4]. These conventional treatment modes, are known to induce multiple side effects that can have negative long-term effects on a patient’s quality of life [4]

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