Oleogels for the ocular delivery of epalrestat: formulation, in vitro, in ovo, ex vivo and in vivo evaluation

Author:

Kattar AxelORCID,Vivero-Lopez MariaORCID,Concheiro AngelORCID,Mudakavi Rajeev,Chauhan AnujORCID,Alvarez-Lorenzo CarmenORCID

Abstract

AbstractThe ocular administration of lipophilic and labile drugs such as epalrestat, an aldose reductase inhibitor with potential for diabetic retinopathy treatment, demands the development of topical delivery systems capable of providing sufficient ocular bioavailability. The aim of this work was to develop non-aqueous oleogels based on soybean oil and gelators from natural and sustainable sources (ethyl cellulose, beeswax and cocoa butter) and to assess their reproducibility, safety and efficiency in epalrestat release and permeation both ex vivo and in vivo. Binary combinations of gelators at 10% w/w resulted in solid oleogels (oleorods), while single gelator oleogels at 5% w/w remained liquid at room temperature, with most of the oleogels displaying shear thinning behavior. The oleorods released up to 4 µg epalrestat per mg of oleorod in a sustained or burst pattern depending on the gelator (approx. 10% dose in 24 h). The HET-CAM assay indicated that oleogel formulations did not induce ocular irritation and were safe for topical ocular administration. Corneal and scleral ex vivo assays evidenced the permeation of epalrestat from the oleorods up to 4 and 2.5 µg/cm2 after six hours, respectively. Finally, the capacity of the developed oleogels to sustain release and provide significant amounts of epalrestat to the ocular tissues was demonstrated in vivo against aqueous-based niosomes and micelles formulations loaded with the same drug concentration. Overall, the gathered information provides valuable insights into the development of oleogels for ocular drug delivery, emphasizing their safety and controlled release capabilities, which have implications for the treatment of diabetic neuropathy and other ocular conditions. Graphical abstract

Funder

Universidade de Santiago de Compostela

Publisher

Springer Science and Business Media LLC

Reference74 articles.

1. European Commission The 2021 Aeging Report; 2021. https://ec.europa.eu/info/publications/2021-ageing-report-economic-and-budgetary-projections-eu-member-states-2019-2070_en.

2. Laiteerapong N, Huang ES. Diabetes in America; chap. 16 diabetes in older adults. 3rd ed. NIDDK; 2018.

3. Lorenzi M. The Polyol Pathway as a mechanism for Diabetic Retinopathy: attractive, elusive, and resilient. Exp Diabetes Res. 2007;2007:1–10. https://doi.org/10.1155/2007/61038.

4. Tang WH, Martin KA, Hwa JA, Reductase. Oxidative stress, and Diabetic Mellitus. Front Pharmacol. 2012;3:1–8. https://doi.org/10.3389/fphar.2012.00087.

5. Taylor R, Agius L. The biochemistry of diabetes. J Biochem. 1988;250:625–40.

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