title: Application of multiple stepwise spinning disk processing for the synthesis of poly(methyl acrylates) coated chitosan-diclofenac sodium nanoparticles for colonic drug delivery.
abstract: The production of pharmaceutical nanoparticles by the spinning disk processing (SDP) technique has advantages in terms of its scalability and its capacity to produce readily tunable nanoparticles of narrow size distribution. In this study, we successfully developed a novel multiple stepwise SDP technique to develop aggregates of uniformly sized poly(methyl acrylates)-coated chitosan-diclofenac sodium nanocores (CS-PMA NPs) for colonic drug delivery. The processing conditions were optimized using the Box-Behnken design. SEM and TEM micrographs showed the optimized system to consist of 10 μm-sized agglomerates of CS-PMA NPs, the latter measuring 10nm in diameter. High drug entrapment of 88% was attained. Potential colon-targeted drug release from the CS-PMA NPs was demonstrated, with retardation of drug release in simulated gastrointestinal fluids and over 90% of the drug load released into simulated colonic fluid within 8 h. Drug uptake from CS-PMA NPs into Caco-2 cells was threefold higher than that from a control drug solution, with no apparent cytotoxicity observed at the NP doses administered. The collective data suggest that the SDP is a robust manufacturing method that can potentially be used to scale up the production of composite nanoparticulate colon-targeted drug delivery systems.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
authors.forename: Kampanart
authors.initials: K
authors.lastname: Huanbutta
authors.forename: Pornsak
authors.initials: P
authors.lastname: Sriamornsak
authors.forename: Manee
authors.initials: M
authors.lastname: Luangtana-Anan
authors.forename: Sontaya
authors.initials: S
authors.lastname: Limmatvapirat
authors.forename: Satit
authors.initials: S
authors.lastname: Puttipipatkhachorn
authors.forename: Lee-Yong
authors.initials: LY
authors.lastname: Lim
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
authors.forename: Jurairat
authors.initials: J
authors.lastname: Nunthanid
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry*; D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry*; D003106:Colon / Q000378:metabolism; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011109:Polymethacrylic Acids; D004008:Diclofenac; D048271:Chitosan
keywords: Box–Behnken design; Chitosan nanoparticles; Colonic drug delivery; Spinning disk processing