title: Positively charged amphiphilic chitosan derivative for the transscleral delivery of rapamycin.
abstract: OBJECTIVE
  We explored the potential of an amphiphilic chitosan derivative to facilitate the transscleral delivery of rapamycin, a potential multitherapeutic agent with poor water solubility.
  
  
  METHODS
  The amphiphilic chitosan derivative, O-octanoyl-chitosan-polyethylene glycol (OChiPEG) graft copolymer, was analyzed using Fourier-transform infrared spectroscopy (FT-IR). OChiPEG micelles were prepared via the thin film method and characterized for their size using dynamic light scattering (DLS), zeta potential using laser Doppler velocimetry (LDV), morphology using transmission electron microscopy (TEM), drug entrapment efficiency (EE), and drug loading (DL) efficiency using reversed-phase high performance liquid chromatography (RP-HPLC), critical micelle concentration (CMC) using spectrofluorometry, and thermal properties using differential scanning calorimetry (DSC) and x-ray powder diffraction (XRPD). Scleral permeation and retention of rapamycin from the drug-loaded micelles were determined in porcine sclera clamped in Ussing chambers, using RP-HPLC.
  
  
  RESULTS
  Conjugation of hydrophilic and hydrophobic groups to chitosan was confirmed using FT-IR. Rapamycin-loaded micelles of particle size 40.6 nm and zeta potential + 6.84 mV were prepared successfully. These carriers exhibited a high EE and DL of 85.6 and 16.3%, respectively, and a CMC of 16.6 μM. OChiPEG micelles showed a high rapamycin scleral retention (14.8 ± 0.81 μg/g) with successful transscleral permeation (5.57 ± 1.04 × 10(-8) cm(2) · s(-1)).
  
  
  CONCLUSIONS
  Positively charged OChiPEG micelles loaded with rapamycin were prepared successfully. These showed a high scleral retention and successful permeation of rapamycin, and therefore may be useful for the topical delivery of other hydrophobic agents.
authors.affiliation: University College London, School of Pharmacy, London, United Kingdom.
authors.forename: Naba
authors.initials: N
authors.lastname: Elsaid
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Jackson
authors.forename: Mirza
authors.initials: M
authors.lastname: Gunic
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Somavarapu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D017078:Laser-Doppler Flowmetry; D008027:Light; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry*; D012542:Scattering, Radiation; D012590:Sclera / Q000187:drug effects*; D020123:Sirolimus / Q000008:administration & dosage*; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents / Q000737:chemistry*; D034421:Sus scrofa; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D008823:Micelles; C508427:PEG-graft-trimethyl-chitosan copolymer; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D048271:Chitosan; D020123:Sirolimus