title: A smart micellar system with an amine-containing polycarbonate shell.
abstract: The present paper reports the design and preparation of an amphiphilic triblock co-polymer poly(ε-caprolactone) (PCL)-poly(6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione) (PADMC)-PCL and the use of micelles composed of them as carriers for pH-sensitive drug release. The triblock co-polymers were synthesized via two-step ring-opening polymerization with catalysis by Novozym-435 lipase. By adjusting the feed ratio, three co-polymers with different PCL lengths and the same PADMC length were produced. The block structure of the co-polymers obtained was confirmed by comparative studies on PCL-PADMC-PCLs and the corresponding random poly(ε-caprolactone-random-6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione) (poly(CL-r-ADMC)) by means of nuclear magnetic resonance and differential scanning calorimetry. Cell cytotoxicity tests showed that the co-polymer displayed no apparent cytotoxicity to 293T and HeLa cells. Transmissions electron microscopy indicates that the self-assembled micelles exhibited a well-defined spherical shape with a diameter between ∼30 and 50 nm. The critical aggregation concentration was dependent on the block composition. Due to the presence of ionizable tertiary amine groups in the PADMC block, acid-induced variation in the micellar morphology was evident with respect to micelle size and size distribution. The size-pH curve was characterized by a smooth sigmoid form, and had a dramatic upward shift with decreasing pH from 6.5 to 4.5, which correlated well with the buffer range of hydrophilic PADMC. As a demonstration of the potential of PCL-PADMC-PCL micelles to control drug delivery, acid induced drug release for prednisone acetate-loaded micelles was explored. PCL-PADMC-PCL micelles show good promise as smart drug carriers, sensing the local specific pH decrease around lesion sites.
authors.affiliation: Key Laboratory of Biomedical Polymers, Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
authors.forename: Hua-Fen
authors.initials: HF
authors.lastname: Wang
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Luo
authors.forename: Chen-Wei
authors.initials: CW
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
mesh_terms: D000588:Amines / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D034261:Epothilones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005453:Fluorescence; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D057446:Hydrodynamics; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D011076:Polycarboxylate Cement / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D058105:Polymerization / Q000187:drug effects; D011241:Prednisone / Q000494:pharmacology; D012542:Scattering, Radiation; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D000588:Amines; D034261:Epothilones; D008823:Micelles; D011076:Polycarboxylate Cement; D011091:Polyesters; D014867:Water; C016240:polycaprolactone; C005506:polycarbonate; D011241:Prednisone