可注射式雙性幾丁聚醣奈米凝膠用於青光眼藥物緩釋型治療之開發與研究

Abstract

According to the World Health Organization (WHO), glaucoma is second only to cataracts as leading cause of global blindness. Glaucoma administration through ophthalmic solutions (eye drops) that can lower the intraocular pressure (IOP) has some problems including poor patient compliance and low bioavailability. In this study, a novel injectable anti-glaucoma nanogel was prepared by combining an amphiphilic chitosan (CHC) with an anti-glaucoma drug, latanoprost. The injectable anti-glaucoma nanogel was injected into subconjunctival region, which provided a localized, long-term, and sustained release of latanoprost that can be used in the glaucoma treatment. The rheological behavior of the colloidal nanogel was observed to affect the rigidity of colloidal nanogel in the presence of a stabilizer of latanoprost,, as BAK, while influencing subsequent drug release profile. In rheological test, the colloidal nanogel was found to rapidly recover to its original gel state after a high shear strain induced structural breakdown, indicating the colloidal nanogel to be provided with excellent recovery property. The drug release behavior of different compositions and procedures colloidal nanogel was evaluated. The stability of latanoprost within nanogels under three temperature conditions were investigated by LC/MS. In vitro cell cytotoxicity and in-vivo evaluation of the colloidal nanogel was observed to exhibit excellent bio-compatibility with Statens Seruminstitut rabbit cornea (SIRC) cells, and both skin and eye of rabbits. iv Finally, latanoprost was observed to distinctly deliver from the nanogel to conjunctival tissues and eye tissues, and transformed into biologically active latanoprost acid. In intraocular pressure (IOP) test, the latanoprost-loaded CHC nanogel was observed to effectively reduce IOP. These experimental outcomes clearly demonstrated a promising injectable latanoprost-containing drug depot with sustained release for anti-glaucoma treatment. Moreover, this newly-designed injectable drug delivery depot should be highly efficient in improving patient compliance, while also increasing the bioavailability of the latanprost comparing to other existing dosing strategy.

According to the World Health Organization (WHO), glaucoma is second only to cataracts as leading cause of global blindness. Glaucoma administration through ophthalmic solutions (eye drops) that can lower the intraocular pressure (IOP) has some problems including poor patient compliance and low bioavailability. In this study, a novel injectable anti-glaucoma nanogel was prepared by combining an amphiphilic chitosan (CHC) with an anti-glaucoma drug, latanoprost. The injectable anti-glaucoma nanogel was injected into subconjunctival region, which provided a localized, long-term, and sustained release of latanoprost that can be used in the glaucoma treatment. The rheological behavior of the colloidal nanogel was observed to affect the rigidity of colloidal nanogel in the presence of a stabilizer of latanoprost,, as BAK, while influencing subsequent drug release profile. In rheological test, the colloidal nanogel was found to rapidly recover to its original gel state after a high shear strain induced structural breakdown, indicating the colloidal nanogel to be provided with excellent recovery property. The drug release behavior of different compositions and procedures colloidal nanogel was evaluated. The stability of latanoprost within nanogels under three temperature conditions were investigated by LC/MS. In vitro cell cytotoxicity and in-vivo evaluation of the colloidal nanogel was observed to exhibit excellent bio-compatibility with Statens Seruminstitut rabbit cornea (SIRC) cells, and both skin and eye of rabbits. iv Finally, latanoprost was observed to distinctly deliver from the nanogel to conjunctival tissues and eye tissues, and transformed into biologically active latanoprost acid. In intraocular pressure (IOP) test, the latanoprost-loaded CHC nanogel was observed to effectively reduce IOP. These experimental outcomes clearly demonstrated a promising injectable latanoprost-containing drug depot with sustained release for anti-glaucoma treatment. Moreover, this newly-designed injectable drug delivery depot should be highly efficient in improving patient compliance, while also increasing the bioavailability of the latanprost comparing to other existing dosing strategy.