Electrohydrodynamic fabrication of core–shell PLGA nanoparticles with controlled release of cisplatin for enhanced cancer treatment

Abstract

Philip JT Reardon,1,* Maryam Parhizkar,2,* Anthony H Harker,3 Richard J Browning,4 Vessela Vassileva,5 Eleanor Stride,4 R Barbara Pedley,5 Mohan Edirisinghe,2 Jonathan C Knowles1 1Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, 2Department of Mechanical Engineering, 3Department of Physics & Astronomy, University College London, London, 4Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, 5Department of Oncology, UCL Cancer Institute, University College London, London, UK *These authors contributed equally to this work Abstract: Increasing the clinical efficacy of toxic chemotherapy drugs such as cisplatin (CDDP), via targeted drug delivery, is a key area of research in cancer treatment. In this study, CDDP-loaded poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles (NPs) were successfully prepared using electrohydrodynamic atomization (EHDA). The configuration was varied to control the distribution of CDDP within the particles, and high encapsulation efficiency (>70%) of the drug was achieved. NPs were produced with either a core–shell (CS) or a matrix (uniform) structure. It was shown that CS NPs had the most sustained release of the 2 formulations, demonstrating a slower linear release post initial “burst” and longer duration. The role of particle architecture on the rate of drug release in vitro was confirmed by fitting the experimental data with various kinetic models. This indicated that the release process was a simple diffusion mechanism. The CS NPs were effectively internalized into the endolysosomal compartments of cancer cells and demonstrated an increased cytotoxic efficacy (concentration of a drug that gives half maximal response [EC50] reaching 6.2 µM) compared to free drug (EC50 =9 µM) and uniform CDDP-distributed NPs (EC50 =7.6 µM) in vitro. Thus, these experiments indicate that engineering the structure of PLGA NPs can be exploited to control both the dosage and the release characteristics for improved clinical chemotherapy treatment. Keywords: cisplatin, drug delivery, cancer chemotherapy, polymer, poly(lactic-co-glycolic acid), nanoparticles, electrohydrodynamic atomization, controlled release

Keywords

• cisplatin
• drug delivery
• cancer chemotherapy
• polymer
• Poly (lactic-co-glycolic acid
• nanoparticles
• electrohydrodynamic atomization
• controlled release