Department of Ophthalmology, Jacobs Retina Center at the University of California-San Diego, La Jolla, CA 92093, USA.
Invest Ophthalmol Vis Sci. 2013 Feb 1;54(2):1268-79. doi: 10.1167/iovs.12-11172.
To test the feasibility of covalent loading of daunorubicin into oxidized porous silicon (OPS) and to evaluate the ocular properties of sustained delivery of daunorubicin in this system.
Porous silicon was heat oxidized and chemically functionalized so that the functional linker on the surface was covalently bonded with daunorubicin. The drug loading rate was determined by thermogravimetric analysis. Release of daunorubicin was confirmed in PBS and excised rabbit vitreous by mass spectrometry. Daunorubicin-loaded OPS particles (3 mg) were intravitreally injected into six rabbits, and ocular properties were evaluated through ophthalmic examinations and histology during a 3-month study. The same OPS was loaded with daunorubicin using physical adsorption and was evaluated similarly as a control for the covalent loading.
In the case of covalent loading, 67 ± 10 μg daunorubicin was loaded into each milligram of the particles while 27 ± 10 μg/mg particles were loaded by physical adsorption. Rapid release of daunorubicin was observed in both PBS and excised vitreous (~75% and ~18%) from the physical adsorption loading, while less than 1% was released from the covalently loaded particles. Following intravitreal injection, the covalently loaded particles demonstrated a sustained degradation of OPS with drug release for 3 months without evidence of toxicity; physical adsorption loading revealed a complete release within 2 weeks and localized retinal toxicity due to high daunorubicin concentration.
OPS with covalently loaded daunorubicin demonstrated sustained intravitreal drug release without ocular toxicity, which may be useful to inhibit unwanted intraocular proliferation.
测试阿霉素共价载入氧化多孔硅（OPS）的可行性，并评估该系统中阿霉素持续释放的眼部特性。
多孔硅经热氧化和化学功能化处理，使表面的功能连接子与阿霉素发生共价键合。通过热重分析测定药物载药量。通过质谱法在 PBS 和离体兔玻璃体内确证阿霉素的释放。将 3mg 载有阿霉素的 OPS 颗粒（3mg）眼内注射到 6 只兔子中，通过眼科检查和 3 个月的研究中的组织学评估眼部特性。将相同的 OPS 用物理吸附法载入阿霉素作为共价载入的对照进行类似评估。
在共价载入的情况下，每毫克颗粒中载入了 67±10μg 的阿霉素，而通过物理吸附载入的颗粒则为 27±10μg/mg。在 PBS 和离体玻璃体中均观察到物理吸附载入的阿霉素快速释放（约 75%和 18%），而共价载入的颗粒中释放量不到 1%。玻璃体内注射后，共价载入的颗粒在 3 个月内表现出 OPS 的持续降解和药物释放，无毒性证据；物理吸附载入的颗粒在 2 周内完全释放，并由于高浓度的阿霉素而导致局部视网膜毒性。
共价载入阿霉素的 OPS 表现出持续的眼内药物释放而无眼毒性，这可能有助于抑制眼内不需要的增殖。
