title: The use of nano polymeric self-assemblies based on novel amphiphilic polymers for oral hydrophobic drug delivery.
abstract: OBJECTIVE
  To investigate the use of nano self-assemblies formed by polyallylamine (PAA) modified with 5 or 10% mole fluorenylmethoxy carbonyl (Fmoc(5)/(10)), dimethylamino-1-naphthalenesulfonyl (Dansyl(5)/(10)) and 5% mole cholesteryl group (Ch(5)) for oral hydrophobic drug delivery.
  
  
  METHODS
  Propofol, griseofulvin and prednisolone were loaded into amphiphilic PAAs. Particle size and morphology of drug-loaded self-assemblies were determined using photon correlation spectroscopy and transmission electron microscopy. Solubilising capacity, in vitro drug release and formulation stability were analysed by HPLC, and in vitro biocompatibility studies (haemolysis and cytotoxicity) were carried out on bovine erythrocytes and Caco-2 cells, respectively. Dansyl(10) and Ch(5) griseofulvin formulations were administered intra-gastrically to rats, and drug plasma levels were analysed by HPLC.
  
  
  RESULTS
  Drug-encapsulated self-assemblies typically have hydrodynamic size of 300-400 nm. Dansyl(10) exhibited universal drug solubiliser property and had significantly improved prednisolone, griseofulvin and propofol solubility by 145, 557 and 224-fold, respectively. Fmoc polymers resulted in modest drug solubility improvement. These polymers were non-haemolytic, did not enhance cytotoxicity compared to unmodified PAA, and demonstrated significant increase in griseofulvin plasma concentration compared to griseofulvin in water after oral administration.
  
  
  CONCLUSIONS
  Ch(5) and Dansyl(10) showed promising potential as nano-carriers for oral hydrophobic drug delivery.
authors.affiliation: School of Pharmacy and Life Sciences, The Robert Gordon University St Andrew St, Aberdeen, AB25 1HG, UK.
authors.forename: Hoskins
authors.initials: H
authors.lastname: Clare
authors.forename: Paul Kong Thoo
authors.initials: PK
authors.lastname: Lin
authors.forename: Laurence
authors.initials: L
authors.lastname: Tetley
authors.forename: Woei Ping
authors.initials: WP
authors.lastname: Cheng
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018938:Caco-2 Cells; D002417:Cattle; D002470:Cell Survival; D002782:Cholestenes / Q000737:chemistry / Q000633:toxicity; D003619:Dansyl Compounds / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D005449:Fluorenes / Q000737:chemistry / Q000633:toxicity; D006118:Griseofulvin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D011073:Polyamines / Q000737:chemistry* / Q000633:toxicity; D011239:Prednisolone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015742:Propofol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D002782:Cholestenes; D003619:Dansyl Compounds; D004337:Drug Carriers; D005449:Fluorenes; D006993:Hypnotics and Sedatives; D011073:Polyamines; C063994:polyallylamine; D006118:Griseofulvin; D011239:Prednisolone; D015742:Propofol