RT Journal Article
T1 Oleogels for the ocular delivery of epalrestat: formulation, in vitro, in ovo, ex vivo and in vivo evaluation
A1 Kattar, Axel
A1 Vivero López, María
A1 Concheiro Nine, Ángel Joaquín
A1 Mudakavi, Rajeed
A1 Chauhan, Anuj
A1 Álvarez Lorenzo, Carmen
K1 Oleogel
K1 Epalrestat
K1 Ocular delivery
K1 Diabetes
K1 Topical administration
K1 Ocular biodistribution
AB The 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.
PB Springer
YR 2024
FD 2024-05-23
LK http://hdl.handle.net/10347/34263
UL http://hdl.handle.net/10347/34263
LA eng
NO Kattar, A., Vivero-Lopez, M., Concheiro, A. et al. Oleogels for the ocular delivery of epalrestat: formulation, in vitro, in ovo, ex vivo and in vivo evaluation. Drug Deliv. and Transl. Res. (2024). https://doi.org/10.1007/s13346-024-01560-7
NO This research was funded by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Actions (grant agreement-No 813440). The work was also supported by MCIN/AEI/10.13039/501100011033 [PID 2020-113881RB-I00] Spain, Xunta de Galicia [ED431C 2020/17] and FEDER. The work was also supported by the NIH award R01EY034477, Back of the eye drug delivery: Novel contact lenses, pathways, and in-silico modeling.
DS Minerva
RD 24 abr 2026