Systematic optimization of cationic surface engineered mucoadhesive vesicles employing Design of Experiment (DoE): A preclinical investigation

Int J Biol Macromol. 2019 Jul 15:133:1142-1155. doi: 10.1016/j.ijbiomac.2019.04.118. Epub 2019 Apr 17.

Abstract

Fungal keratitis (FK) is treated by topical natamycin (Nat) which is an effective antifungal agent. However, it has numerous therapeutic limitations i.e. toxicity, tolerance, need of frequent dosing and patient incompliance. The aim of the present study was to develop Nat loaded trimethyl chitosan (TMC) coated mucoadhesive cationic niosomes (Muc-Cat-Nios) for prolonged and effective delivery to eyes. Niosomes were prepared using thin film hydration method and optimized using a Box-Behnken design (BBD) with the help of Design-Expert® Software. Three independent variables were considered: amount of Span 60 (X1), amount of Cholesterol [Chol(X2)] and TMC concentration (X3). The encapsulation efficiency (R1: EE%), vesicle size (R2: VS) and Zeta potential (R3: ZP) were selected as dependent variables or responses. The optimized Nios displayed spherical shape, 1034.14 nm vesicle size and 81.76% EE. Nat loaded niosomes were incubated with TMC to get mucoadhesive cationic vesicular system. Uncoated and TMC coated niosomes were characterized for mucoadhesive properties, in vitro drug release, rheological behaviour, and ex vivo permeation studies. Cationic Nios showed greater mucoadhesive potential that provided drug release for a long period of time. The promising outcomes suggest that natamycin delivery using cationic mucoadhesive niosomes could be employed for the effective treatment of fungal keratitis.

Keywords: Fungal keratitis; Ocular drug delivery; TMC coated niosomes.

MeSH terms

  • Adhesiveness
  • Animals
  • Chitosan / chemistry
  • Cornea / metabolism
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Engineering*
  • Goats
  • Liposomes / chemistry*
  • Mucous Membrane / chemistry*
  • Natamycin / chemistry
  • Natamycin / metabolism
  • Rheology
  • Surface Properties

Substances

  • Drug Carriers
  • Liposomes
  • N-trimethyl chitosan chloride
  • Natamycin
  • Chitosan