Inulin-Based Polymeric Micelles Functionalized with Ocular Permeation Enhancers: Improvement of Dexamethasone Permeation/Penetration through Bovine Corneas

• Main Authors: Giulia Di Prima, Mariano Licciardi, Flavia Bongiovì, Giovanna Pitarresi, Gaetano Giammona
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: Pharmaceutics
• Subjects: ocular drug delivery; inulin; permeation enhancers; taurine; PEG₂₀₀₀; carnitine
• Online Access: https://www.mdpi.com/1999-4923/13/9/1431

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.