Preparation and in vivo and ex vivo studies of sirolimus nano-in-situ gel ophthalmic formulation

被引:0
|
作者
Liu, Ye [1 ]
Chen, Xu [1 ]
Chen, Xinghao [1 ]
Chen, Jie [1 ]
Zhang, Han [1 ]
Xu, Haonan [1 ]
Jin, Lu [1 ]
Wang, Qiao [1 ,2 ]
Tang, Zhan [1 ,2 ]
机构
[1] Hangzhou Med Coll, Sch Pharm, Hangzhou 310013, Peoples R China
[2] Hangzhou Med Coll, Key Lab Neuropsychiat Drug Res Zhejiang Prov, Hangzhou 310013, Peoples R China
关键词
Sirolimus; Ionomer in situ gel; Gellan gum; Pharmacokinetics; Corneal neovascularization; ENDOTHELIAL GROWTH-FACTOR; CORNEAL NEOVASCULARIZATION; RAPAMYCIN; PHARMACOKINETICS; RELEASE;
D O I
10.1186/s12951-024-02668-1
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Sirolimus (SR) is a macrolide with antifungal and antitumor immunosuppressant properties, classified as a selective inhibitor of mammalian target of rapamycin (mTOR). In this study, an ionic in situ gel of SR (SR-SUS-ISG) was formulated using gellan gum, exhibiting stability regardless of temperature and pH variations, causing minimal irritation. Harnessing the physiological conditions of the eye, SR-SUS-ISG underwent gelation upon contact with ions, increasing drug viscosity and prolonging retention on the ocular surface. Concurrently, SR-SUS-ISG displayed favorable shear dilution properties, reducing viscosity at ambient temperature, enhancing fluidity, and facilitating convenient packaging and transport. Biocompatibility assessments on both human corneal epithelial cells and rabbit eyes demonstrated that SR-SUS-ISG could well be tolerated. Pharmacokinetic investigations in rabbit ocular aqueous humor revealed sustained release, improved corneal penetration, and enhanced bioavailability. Additionally, in a rat corneal alkali burn model, SR-SUS-ISG exhibited inhibitory effects on corneal neovascularization, associated with decreased levels of the inflammatory factors VEGF and MMPs. These findings suggested that SR-SUS-ISG held promise as an effective ocular drug delivery system.
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页数:17
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