title: Double-Walled Microparticles-Embedded Self-Cross-Linked, Injectable, and Antibacterial Hydrogel for Controlled and Sustained Release of Chemotherapeutic Agents.
abstract: First-line cancer chemotherapy has been prescribed for patients suffered from cancers for many years. However, conventional chemotherapy provides a high parenteral dosage of anticancer drugs over a short period, which may cause serious toxicities and detrimental side effects in healthy tissues. This study aims to develop a new drug delivery system (DDS) composed of double-walled microparticles and an injectable hydrogel for localized dual-agent drug delivery to tumors. The uniform double-walled microparticles loaded with cisplatin (Cis-DDP) and paclitaxel (PTX) were fabricated via coaxial electrohydrodynamic atomization (CEHDA) technique and subsequently were embedded into injectable alginate-branched polyethylenimine. The findings show the uniqueness of CEHDA technique for simply swapping the place of drugs to achieve a parallel or a sequential release profile. This study also presents the simulation of CEHDA technique using computational fluid dynamics (CFD) that will help in the optimization of CEHDA's operating conditions prior to large-scale production of microparticles. The new synthetic hydrogel provides an additional diffusion barrier against Cis-DDP and confines premature release of drugs. In addition, the hydrogel can provide a versatile tool for retaining particles in the tumor resected cavity during the injection after debulking surgery and preventing surgical site infection due to its inherent antibacterial properties. Three-dimensional MDA-MB-231 (breast cancer) spheroid studies demonstrate a superior efficacy and a greater reduction in spheroid growth for drugs released from the proposed composite formulation over a prolonged period, as compared with free drug treatment. Overall, the new core-shell microparticles embedded into injectable hydrogel can serve as a flexible controlled release platform for modulating the release profiles of anticancer drugs and subsequently providing a superior anticancer response.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore , 4 Engineering Drive 4, Singapore 117585.
authors.forename: Pooya
authors.initials: P
authors.lastname: Davoodi
authors.affiliation: NUS Environmental Research Institute, National University of Singapore , 1 Create Way, Create Tower #15-02, Singapore 138602.
authors.forename: Wei Cheng
authors.initials: WC
authors.lastname: Ng
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore , 4 Engineering Drive 4, Singapore 117585.
authors.forename: Wei Cheng
authors.initials: WC
authors.lastname: Yan
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore , 4 Engineering Drive 4, Singapore 117585.|Civil, Environmental and Chemical Engineering, RMIT University , GPO Box 2476, Melbourne Victoria 3001, Australia.
authors.forename: Madapusi P
authors.initials: MP
authors.lastname: Srinivasan
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore , 4 Engineering Drive 4, Singapore 117585.
authors.forename: Chi-Hwa
authors.initials: CH
authors.lastname: Wang
keywords: 3D tumor spheroids; antibacterial surfaces; core−shell microparticles; dual-agent drug delivery; injectable hydrogels