Lucero-Acuña Armando, Gutiérrez-Valenzuela Cindy Alejandra, Esquivel Reynaldo, Guzmán-Zamudio Roberto
Department of Chemical and Environmental Engineering, University of Arizona Tucson USA
Department of Chemical and Metallurgical Engineering, University of Sonora Hermosillo MEXICO.
RSC Adv. 2019 Mar 15;9(16):8728-8739. doi: 10.1039/c9ra00821g.
In this study we describe a mathematical analysis that considers the temperature effects of the controlled drug release process from biodegradable poly-d,l-lactide--glycolide (PLGA) nanoparticles. Temperature effects are incorporated and applied to two drug release models. The first one consists of a two-stage release process that considers only simultaneous contributions of initial burst and nanoparticle degradation-relaxation (BR model). The second one is a three release stage model that considers, additionally, a simultaneous drug diffusion (BRD model) step. In these models, the temperature dependency of the release parameters, initial burst constant, , the rate of degradation-relaxation constant, , time to achieve 50% of release, , and effective diffusion coefficient constant ( ), are determined using mathematical expressions analogous to the Arrhenius equation. The temperature dependent models are used to analyze the release of previously encapsulated Rhodamine 6G dye as a model drug in polyethylene glycol modified PLGA nanoparticles. The experimental data used to develop the mathematical model was obtained from release studies carried out in phosphate buffer pH 7.4 at 37 °C, 47 °C, and 57 °C. Multiphasic release behaviors with an overall increase rate associated with the incubation temperature were observed. The study incorporates a parametrical analysis that can evaluate diverse temperature variation effects of the controlled release parameters for the two models.
在本研究中，我们描述了一种数学分析方法，该方法考虑了可生物降解的聚-d，l-丙交酯-乙交酯（PLGA）纳米颗粒控释过程中的温度效应。温度效应被纳入并应用于两种药物释放模型。第一个模型由一个两阶段释放过程组成，该过程仅考虑初始突释和纳米颗粒降解-松弛的同时作用（BR模型）。第二个模型是一个三释放阶段模型，此外还考虑了一个同时存在的药物扩散步骤（BRD模型）。在这些模型中，使用类似于Arrhenius方程的数学表达式来确定释放参数的温度依赖性，即初始突释常数、降解-松弛常数的速率、达到50%释放所需的时间以及有效扩散系数常数（）。温度依赖性模型用于分析先前包封的罗丹明6G染料作为模型药物在聚乙二醇修饰的PLGA纳米颗粒中的释放情况。用于建立数学模型的实验数据来自于在37°C、47°C和57°C的pH 7.4磷酸盐缓冲液中进行的释放研究。观察到了与孵育温度相关的总体增加速率的多相释放行为。该研究纳入了参数分析，可评估这两种模型中控释参数的不同温度变化效应。
