Abstract
Ophthalmic drug delivery is still a challenge due to the protective barriers of the eye. A common strategy to promote drug absorption is the use of ocular permeation enhancers, while an innovative approach is the use of polymeric micelles. In the present work, the two mentioned approaches were coupled by conjugating ocular permeation enhancers (PEG2000, carnitine, creatine, taurine) to an inulin-based co-polymer (INU-EDA-RA) in order to obtain self-assembling biopolymers with permeation enhancer properties for the hydrophobic drug dexamethasone (DEX). Inulin derivatives were properly synthetized, were found to expose about 2% mol/mol of enhancer molecules in the side chain, and resulted able to self-assemble at various concentrations by varying the pH and the ionic strength of the medium. Moreover, the ability of polymeric micelles to load dexamethasone was demonstrated, and size, mucoadhesiveness, and cytocompatibility against HCE cells were evaluated. Furthermore, the efficacy of the permeation enhancer was evaluated by ex vivo permeation studies to determine the performance of the used enhancers, which resulted in PEG2000 > CAR > TAU > CRE, while entrapment ability studies resulted in CAR > TAU > PEG2000 > CRE, both for fluorescent-labelled and DEX-loaded micelles. Finally, an increase in terms of calculated Kp and Ac parameters was demonstrated, compared with the values calculated for DEX suspension.
Highlights
Ocular drug delivery has always been a challenge for pharmaceutical technologists due to the presence of various anatomically and physiologically static and dynamic barriers that strongly limit the absorption of active molecules
The previously encouraging results obtained for INU-EDA-retinoic Acid (RA) and INU-EDA-RAPEG micelles as effective innovative drug delivery system (DDS) for promoting the permeation of hydrophobic drugs across the corneal tissue have been here coupled with the “permeation enhancer”
Carnitine, and creatine were selected as potential ocular permeation enhancer molecules due to their ability to interact with their specific transporters located on the corneal surface
Summary
Ocular drug delivery has always been a challenge for pharmaceutical technologists due to the presence of various anatomically and physiologically static and dynamic barriers that strongly limit the absorption of active molecules. Ocular permeation enhancers are molecules that are able to modify the corneal barrier transiently and reversibly, promoting drug entry into the tissue They could be food additives and endogenous molecules that are able to interact with their specific transporters. Another traditional successful strategy to overcome poor permeation across the epithelium is to chemically modify the active compound to enable increased passive transport or to employ the specific transporters located in the corneal tissue [1,2]. This is a key point in the development of effective prodrugs. Prodrugs are bioreversible derivatives that undergo an enzymatic and/or chemical transformation in vivo to release the active
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