Ocular gelling microspheres: in vitro Precorneal retention time and drug permeation through reconstituted corneal epithelium

Purpose: The model drug norfloxacin (NOR)was encapsulated into trehalose (TRH) and hydroxyethylcellulose(NAT) microspheres to obtain a novel gelling ophthalmic delivery system for prolonged release on corneal tissue. Methods: We assessed NOR release from microspheres, prepared by the emulsion-solvent evaporation method. A new in vitro tear turnover model, including inserts containing reconstituted human corneal epithelium (RHC), was designed to evaluate the TRH/NAT microspheres’ precorneal retention time. Bioadhesive properties of TRH/NAT microspheres were validated by using drug-loaded microspheres prepared with gelatine (GLT) commonly used as reference material in adhesion studies. Results: In vitro drug release showed a typical trend of swelling systems. Precorneal retention tests showed that TRH/NAT microspheres maintained fluorescence in tear fluid for 81.7 min, whereas TRH/GLT microspheres and water solution maintained fluorescence for 51.8 and 22.3 min, respectively. NOR released from microspheres permeated throughout RHC slower (Js = 23.08 μ g/cm2h) than NOR from commercial eye drops Js = 42.77 μ g/cm2h) used as the control. Conclusions: Adequate drug concentrations in aqueous humor could be prolonged after the administration of TRH/NAT/NOR microspheres. Good bioadhesive properties of the system and slow drug release on corneal surface might increase ocular NOR bioavailability.