title: Simple Microfluidic Approach to Fabricate Monodisperse Hollow Microparticles for Multidrug Delivery.
abstract: Herein, we report the production of monodisperse hollow microparticles from three different polymers, namely, pH-responsive acetylated dextran and hypromellose acetate succinate and biodegradable poly(lactic-co-glycolic acid), at varying polymer concentrations using a poly(dimethylsiloxane)-based microfluidic device. Hollow microparticles formed during solvent diffusion into the continuous phase when the polymer close to the interface solidified, forming the shell. In the inner part of the particle, phase separation induced solvent droplet formation, which dissolved the shell, forming a hole and a hollow-core particle. Computational simulations showed that, despite the presence of convective recirculation around the droplet, the mass-transfer rate of the solvent dissolution from the droplet to the surrounding phase was dominated by diffusion. To illustrate the potential use of hollow microparticles, we simultaneously encapsulated two anticancer drugs and investigated their loading and release profiles. In addition, by utilizing different polymer shells and polymer concentrations, the release profiles of the model drugs could be tailored according to specific demands and applications. The high encapsulation efficiency, controlled drug release, unique hollow microparticle structure, small particle size (<7 μm), and flexibility of the polymer choice could make these microparticles advanced platforms for pulmonary drug delivery.
authors.affiliation: †Vilnius University Institute of Biotechnology, Vilnius LT-02241, Lithuania.|‡Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland.
authors.forename: Remigijus
authors.initials: R
authors.lastname: Vasiliauskas
authors.affiliation: ‡Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland.
authors.forename: Dongfei
authors.initials: D
authors.lastname: Liu
authors.affiliation: ‡Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cito
authors.affiliation: ‡Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: ‡Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland.
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Shahbazi
authors.affiliation: ‡Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Sikanen
authors.affiliation: †Vilnius University Institute of Biotechnology, Vilnius LT-02241, Lithuania.|§School of Engineering and Applied Physics, Harvard University, Cambridge, Massachusetts 02138, United States.
authors.forename: Linas
authors.initials: L
authors.lastname: Mazutis
authors.affiliation: ‡Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D065966:Absorption, Physicochemical; D002214:Capsules / Q000737:chemistry*; D003198:Computer Simulation; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D004338:Drug Combinations; D004339:Drug Compounding / Q000295:instrumentation*; D015195:Drug Design; D004867:Equipment Design; D019544:Equipment Failure Analysis; D008422:Materials Testing; D044085:Microfluidics / Q000295:instrumentation*; D008956:Models, Chemical; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D016062:Porosity
chemical_list: D002214:Capsules; D004129:Dimethylpolysiloxanes; D004338:Drug Combinations; D011108:Polymers; C013830:baysilon
keywords: PDMS microfluidics; drug delivery; hollow microparticles; multidrug encapsulation; solvent diffusion