Ocular gelling microspheres: in vitro precorneal retention time and drug permeation through reconstituted corneal epithelium.
OBJECTIVE
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 (J(s) = 23.08 microg/cm(2)h) than NOR from commercial eye drops (J(s) = 42.77 microg/cm(2)h) 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.
Giannola
Libero I
LI
Dipartimento di Chimica e Tecnologie Farmaceutiche, Università di Palermo, Palermo, Italy. litagian@unipa.it
de Caro
Viviana
V
Giandalia
Giulia
G
Siragusa
Maria G
MG
Cordone
Lorenzo
L
D000268:Adhesiveness; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D002461:Cell Line, Transformed; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003692:Delayed-Action Preparations; D019573:Epithelium, Corneal / Q000378:metabolism*; D005780:Gelatin / Q000737:chemistry; D005782:Gels / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D008863:Microspheres; D009643:Norfloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009883:Ophthalmic Solutions / Q000737:chemistry; D010539:Permeability; D014199:Trehalose / Q000737:chemistry
D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D005782:Gels; D009883:Ophthalmic Solutions; D005780:Gelatin; D002482:Cellulose; C002283:hydroxyethylcellulose; D014199:Trehalose; D009643:Norfloxacin