title: Microfluidic assembly of monodisperse multistage pH-responsive polymer/porous silicon composites for precisely controlled multi-drug delivery.
abstract: We report an advanced drug delivery platform for combination chemotherapy by concurrently incorporating two different drugs into microcompoistes with ratiometric control over the loading degree. Atorvastatin and celecoxib were selected as model drugs due to their different physicochemical properties and synergetic effect on colorectal cancer prevention and inhibition. To be effective in colorectal cancer prevention and inhibition, the produced microcomposite contained hypromellose acetate succinate, which is insoluble in acidic conditions but highly dissolving at neutral or alkaline pH conditions. Taking advantage of the large pore volume of porous silicon (PSi), atorvastatin was firstly loaded into the PSi matrix, and then encapsulated into the pH-responsive polymer microparticles containing celecoxib by microfluidics in order to obtain multi-drug loaded polymer/PSi microcomposites. The prepared microcomposites showed monodisperse size distribution, multistage pH-response, precise ratiometric controlled loading degree towards the simultaneously loaded drug molecules, and tailored release kinetics of the loaded cargos. This attractive microcomposite platform protects the payloads from being released at low pH-values, and enhances their release at higher pH-values, which can be further used for colon cancer prevention and treatment. Overall, the pH-responsive polymer/PSi-based microcomposite can be used as a universal platform for the delivery of different drug molecules for combination therapy.
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Dongfei
authors.initials: D
authors.lastname: Liu
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhang
authors.forename: Bárbara
authors.initials: B
authors.lastname: Herranz-Blanco
authors.forename: Ermei
authors.initials: E
authors.lastname: Mäkilä
authors.forename: Vesa-Pekka
authors.initials: VP
authors.lastname: Lehto
authors.forename: Jarno
authors.initials: J
authors.lastname: Salonen
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D003460:Crystallization / Q000295:instrumentation / Q000379:methods; D003692:Delayed-Action Preparations / Q000138:chemical synthesis*; D004058:Diffusion; D004339:Drug Compounding / Q000295:instrumentation* / Q000379:methods; D015195:Drug Design; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008422:Materials Testing; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D058726:Nanoconjugates / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D016062:Porosity; D012825:Silicon / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D053769:Nanocapsules; D058726:Nanoconjugates; D011108:Polymers; D012825:Silicon
keywords: controlled drug release; microfluidics; monodisperse composite; pH-responsive; porous silicon