Nanoparticles offer an ideal opportunity for the efficient local anesthetic drug delivery required during and after ocular procedures. Currently available local anesthetic drugs are short acting, which may prevent adequate ocular pain control. Therefore, development of sustained controlled release anesthetic devices for pain control over a relatively short period (up to 48 h) potentially meets various opthalmological analgesic requirements. This study presents preliminary findings for drug delivery using poly(sebacic acid) (PSA) nanoparticles for tetracaine and lidocaine administration. Tetracaine- or lidocaine-loaded PSA nanoparticles were prepared using a double emulsion methodology. Release profiles were similar for both formulations, with 50% cumulative release achieved after 17 h and 23 h for tetracaine and lidocaine, respectively. The release profiles were studied, and data obtained from in vitro experiments were fit to different mathematical models. Based on mathematical models used in this study, drug release from all PSA-based formulations was diffusion-controlled, best described by the Higuchi model. Based on preliminary experiments, a hybrid formulation providing a burst effect was designed to counter the fast adsorption of drug expected in the physiological system. This was achieved by coating the lidocaine-loaded PSA nanoparticles with a gelatin/lidocaine layer. The coating provided accelerated lidocaine release, with 50% cumulative release obtained as early as 7 h compared to 23 h for uncoated nanoparticles. This formulation provided a triphasic release that can treat different pain levels at predetermined timelines. Our results provide new insight into the benefits of using polyanhydrides as a platform for drug delivery in ophthalmology.

中文翻译：

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受控和定时给药：基于聚酐的纳米粒子作为眼部药物载体

纳米颗粒为眼部手术期间和之后所需的有效局部麻醉药物输送提供了理想的机会。目前可用的局部麻醉药物是短效的，这可能会妨碍对眼部疼痛的充分控制。因此，开发用于在相对较短的时间内（长达 48 小时）控制疼痛的持续控释麻醉装置可能会满足各种眼科镇痛要求。本研究展示了使用聚（癸二酸）（PSA）纳米颗粒进行丁卡因和利多卡因给药的药物递送的初步发现。使用双乳液方法制备丁卡因或利多卡因负载的 PSA 纳米颗粒。两种制剂的释放曲线相似，丁卡因和利多卡因分别在 17 小时和 23 小时后达到 50% 的累积释放。研究了释放曲线，并且从体外实验中获得的数据适合不同的数学模型。根据本研究中使用的数学模型，所有基于 PSA 的制剂的药物释放都是受扩散控制的，最好用 Higuchi 模型来描述。基于初步实验，设计了一种提供爆发效应的混合制剂，以对抗生理系统中预期的药物快速吸附。这是通过用明胶/利多卡因层涂覆负载利多卡因的 PSA 纳米颗粒来实现的。涂层提供了加速的利多卡因释放，与未涂层纳米粒子的 23 小时相比，早在 7 小时就获得了 50% 的累积释放。这种配方提供了一种三相释放，可以在预定的时间段内治疗不同的疼痛水平。