Microsphere-loaded dual-response <i>in situ</i> gel for enhanced ocular drug delivery

Jinlan Mao; Kangyiran Pan; Suling Bei; Haidong Guo; Shuai Wang; Bowen Pan; Yuqian Liang; Yiqing Dai; Ilva D. Rupenthal; Li Liu; Xifeng Teng; Dongzhi Hou

doi:10.1016/j.jpha.2026.101593

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Jinlan Mao, Kangyiran Pan, Suling Bei, Haidong Guo, Shuai Wang, Bowen Pan, Yuqian Liang, Yiqing Dai, Ilva D. Rupenthal, Li Liu, Xifeng Teng, Dongzhi Hou. Microsphere-loaded dual-response in situ gel for enhanced ocular drug delivery[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101593

Citation:

Jinlan Mao, Kangyiran Pan, Suling Bei, Haidong Guo, Shuai Wang, Bowen Pan, Yuqian Liang, Yiqing Dai, Ilva D. Rupenthal, Li Liu, Xifeng Teng, Dongzhi Hou. Microsphere-loaded dual-response in situ gel for enhanced ocular drug delivery[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101593

Citation:

Jinlan Mao, Kangyiran Pan, Suling Bei, Haidong Guo, Shuai Wang, Bowen Pan, Yuqian Liang, Yiqing Dai, Ilva D. Rupenthal, Li Liu, Xifeng Teng, Dongzhi Hou. Microsphere-loaded dual-response in situ gel for enhanced ocular drug delivery[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101593

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Microsphere-loaded dual-response in situ gel for enhanced ocular drug delivery

doi: 10.1016/j.jpha.2026.101593

a. Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China;
b. Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand;
c. Guangzhou Huangpu District New Drug Application Service Center, Guangzhou, 510663, China;
d. College of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China

Funds:

This study was supported financially by the National Natural Science Foundation of China (Grant No.: 51192052), the Open Project of Guangdong Provincial Key Laboratory of Mineral Physics and Materials (Grant No.: GLMPM-047), and the Science and Technology Planning Program of Guangdong Province, China (Grant No.: 2020B1212060055). We thank Dr. Qingjun Zhou from Shandong Ophthalmic Research Institute, as well as the Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, the Guangdong Engineering Technology Research Centre for Molecular Probe, and the Biomedicine Imaging and Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems for their help in the experiments.

Received Date: Aug. 10, 2025
Accepted Date: Feb. 24, 2026
Rev Recd Date: Feb. 15, 2026
Available Online: Feb. 28, 2026

Abstract

Abstract

Glaucoma is one of the most common blinding eye diseases worldwide. The limited ocular surface retention leading to a short duration of efficacy is the challenge in topical ocular drug delivery for glaucoma treatment. In this study, we developed a microsphere-in-situ gel composite drug delivery system (MPs-DSISG) containing Eudragit RS PO microspheres and a cation- and temperature-sensitive in situ gel, exhibiting dual-response properties. Precorneal fluorescence retention and tear elimination kinetics experiments confirmed that the ocular residence time of MPs-DSISG was longer than that of commercially available formulations and drug solutions. Besides prolonged retention time, the incorporated microspheres exhibited affinity for corneal epithelial cells and embedded themselves in the superficial layers of the conjunctiva, Tenon’s capsule, episclera, and sclera. This enabled MPs-DSISG to achieve a 24 h intraocular pressure reduction, thus substantially reducing the dosing frequency. MPs-DSISG also demonstrated good biocompatibility‌ without ocular irritation and disturbing the tear film. In conclusion, this study demonstrates that incorporating microspheres into an insitu gel prolonged ocular retention and enhanced sustained drug efficacy, offering a promising improved treatment for anterior segment diseases.
- Microspheres,
- In situ gel,
- Ocular surface retention,
- Betaxolol hydrochloride,
- Timolol maleate

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References(48)

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