title: Acid-cleavable polymeric core-shell particles for delivery of hydrophobic drugs.
abstract: Here we describe the combined use of acid-labile microgel approach and RAFT-mediated seeded dispersion polymerization technique to prepare an acid-cleavable core-shell like polymeric colloidal system for the delivery of hydrophobic drugs at slightly acidic sites. A new bisacrylate acetal crosslinker was copolymerized with n-butyl acrylate (BA) in the presence of a RAFT agent using a dispersion polymerization technique, which yielded crosslinked spherical particles with the size ranging between 150 and 500 nm. The particles were cleaved in a pH-dependent manner similar to the acid-labile hydrolysis behaviour of the crosslinker. In order to mask the hydrophobic surface of the particles, polyethylene glycol acrylate (PEG-A) was grafted onto poly(BA) seed particles via the RAFT agent groups on the particle surface. The acidic-site selective delivery potential of the poly(BA)-g-poly(PEG-A) particles was assessed in-vitro using a lipophilic fluorescent dye as a model hydrophobic drug. Ca. 73% and 34% of the total dye loaded in the particles was found to be released at pH 5.0 and 7.4 in 24 h, respectively. The growth of human neuroblastoma cells was not affected by the incubation with the core-shell particles and their cleavage by-products up to 3 mg/ml concentration. The physicochemical and the functional features support the potential value of the acid-cleavable poly(BA) core-poly(PEG-A) shell particles as carriers for the delivery of hydrophobic drugs at acidic sites.
authors.affiliation: Centre for Advanced Macromolecular Design, CAMD, School of Chemical Sciences and Engineering, The University of New South Wales, Sydney 2052, NSW, Australia.
authors.forename: Yannie
authors.initials: Y
authors.lastname: Chan
authors.forename: Volga
authors.initials: V
authors.lastname: Bulmus
authors.forename: M Hadi
authors.initials: MH
authors.lastname: Zareie
authors.forename: Frances L
authors.initials: FL
authors.lastname: Byrne
authors.forename: Leonie
authors.initials: L
authors.lastname: Barner
authors.forename: Maria
authors.initials: M
authors.lastname: Kavallaris
mesh_terms: D000085:Acetates / Q000737:chemistry; D000143:Acids; D000179:Acrylates / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002850:Chromatography, Gel; D003432:Cross-Linking Reagents; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013052:Spectrometry, X-Ray Emission; D014867:Water
chemical_list: D000085:Acetates; D000143:Acids; D000179:Acrylates; D003432:Cross-Linking Reagents; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D004364:Pharmaceutical Preparations; D011108:Polymers; D014867:Water; D011092:Polyethylene Glycols; C006848:butyl acetate