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Abstract
The purpose of this study was to develop poloxamer (P407)-based in-situ thermogellable hydrogels with reducing concentration of P407 by adding hypromellose (HPMC) and with enhancing mucoadhesion of resulting hydrogels by adding hyaluronic acid (HA) for prolonging ocular delivery of hydroxypropyl-β-cyclodextrin (HPβCD)-solubilized testosterone (TES). Results demonstrated that 0.5% TES solution was successfully solubilized with adding 10% HPβCD. Non-gellable 13% P407 sol became in-situ gellable with adding 2.0-2.5% HPMC and mucoadhesibility was further imporved with adding 0.3% HA-L (low MW) or HA-H (high MW). Optimized 0.5% HPβCD-solubilized TES P407-based thermogellable hydrogels with enhancement of mucoadhesion for prolonging ocular delivery comprised 13% P407, 2.5% HPMC, and 0.3% HA-L or HA-H. Furthermore, rheological measurements under simulated eye blinking confirmed that non-thixotropic properties of optimized hydrogels could be spreaded evenly and retain a greater amount of drug-loaded hydrogels on the ocular surface for a longer period to prolong drug delivery. Compared with conventional eye drops, the prolonged residence time of optimized hydrogels from ex vivo and in vivo studies were observed, indicating relationships between rheological properties and in vivo performances. It was concluded that P407-based thermosensitive hydrogels with reducing concentration of P407 and enhancing mucoadhesion was successfully formulated by adding 2.5% HPMC and 0.3% HA in 13% P407 for potentially accomplishing effective clinical treatment of DED.
Disclosure statement
No potential conflict of interest was reported by the authors.
This study was partially supported by research grants from the Ministry of Science and Technology of the Republic of China (MOST 109-2314-B-264-001, MOST 109-2320-B-037-018) and Jin-lung-yuan Foundation (2022-2023).
CRediT authorship contribution statement
Ling-Chun Chen: Investigation, Formal analysis, Visualization, Writing-original draft. Shyr-Yi Lin: Funding acquisition, Project administration, Resources. Ming-Thau Sheu: Conceptualization, Project administration, Resources, Supervision, Writing—review & editing. Chi-Yun Chung: Investigation, Formal analysis, Validation, Methodology. Wei-Jie Cheng: Methodology, Investigation, Formal analysis. Hong-Liang Lin: Conceptualization, Investigation, Formal analysis, Methodology, Project administration, Supervision, Validation, Visualization, Writing—review & editing.