title: Chirality plays critical roles in enhancing the aqueous solubility of nocathiacin I by block copolymer micelles.
abstract: OBJECTIVE
  Although drug solubilization by block copolymer micelles has been extensively studied, the rationale behind the choice of appropriate block copolymer micelles for various poorly water-soluble drugs has been of relatively less concern. The objective of this study was to use methoxy-poly(ethylene glycol)-polylactate micelles (MPEG-PLA) to solubilize glycosylated antibiotic nocathiacin I and to compare the effects of chirality on the enhancement of aqueous solubility.
  
  
  METHODS
  Nocathiacin I-loaded MPEG-PLA micelles with opposite optical property in PLA were synthesized and characterized. The drug release profile, micelle stability and preliminary safety properties of MPEG-PLA micelles were evaluated. Meanwhile, three other poorly water-soluble chiral compound-loaded micelles were also prepared and compared.
  
  
  RESULTS
  The aqueous solubility of nocathiacin I was greatly enhanced by both L- and D-copolymers, with the degree of enhancement appearing to depend on the chirality of the copolymers. Comparison of different chiral compounds confirmed the trend that aqueous solubility of chiral compounds can be more effectively enhanced by block copolymer micelles with specific stereochemical configuration.
  
  
  CONCLUSIONS
  The present study introduced chiral concept on the selection and preparation of block copolymer micelles for the enhancement of aqueous solubility of poorly water-soluble drugs.
authors.affiliation: State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Feng
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Wang
authors.forename: Hairong
authors.initials: H
authors.lastname: Ma
authors.forename: Yijun
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000192:Actinomycetales / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D004355:Drug Stability; D006031:Glycosylation; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D007773:Lactates / Q000009:adverse effects / Q000737:chemistry; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D011091:Polyesters / Q000009:adverse effects / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry*; D055550:Protein Stability; D012995:Solubility; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004337:Drug Carriers; D036341:Intercellular Signaling Peptides and Proteins; D007773:Lactates; D008823:Micelles; D010455:Peptides; D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); C463319:nocathiacin I; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols