Nanoparticle formulations have found increasing applications in modern therapies. To achieve desired treatment efficacy and safety profiles, drug release kinetics of nanoparticles must be controlled tightly. However, actual drug release kinetics of nanoparticles cannot be readily measured due to technique difficulties, although various methods have been attempted. Among existing experimental approaches, dialysis method is the most widely applied one due to its simplicity and avoidance of separating released drug from the nanoparticles. Yet this method only measures the released drug in the medium outside a dialysis device (the receiver), instead of actual drug release from the nanoparticles inside the dialysis device (the donor). Thus we proposed a new method using numerical deconvolution to evaluate actual drug release kinetics of nanoparticles inside the donor based on experimental release profiles of nanoparticles and free drug solution in the receptor determined by existing dialysis tests. Two computer programs were developed based on two different numerical methods, namely least square criteria with prescribed Weibull function or orthogonal polynomials as input function. The former was used for all analyses in this work while the latter for verifying the reliability of the predictions. Experimental data of drug release from various nanoparticle formulations obtained from different dialysis settings and membrane pore sizes were used to substantiate this approach. The results demonstrated that this method is applicable to a broad range of nanoparticle and microparticle formulations requiring no additional experiments. It is independent of particle formulations, drug release mechanisms, and testing conditions. This new method may also be used, in combination with existing dialysis devices, to develop a standardized method for quality control, in vitro-in vivo correlation, and for development of nanoparticles and other types of dispersion formulations.

中文翻译：

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一种通过数值反卷积评估透析装置内部纳米粒子实际药物释放动力学的新方法

纳米颗粒制剂已发现在现代疗法中越来越多的应用。为了获得所需的治疗功效和安全性，必须严格控制纳米颗粒的药物释放动力学。然而，尽管已经尝试了各种方法，但是由于技术困难，纳米颗粒的实际药物释放动力学不能容易地测量。在现有的实验方法中，透析方法由于其简单性和避免了将释放的药物与纳米颗粒分离而成为应用最广泛的方法。然而，该方法仅测量透析装置（接收器）外部介质中的释放药物，而不是从透析装置（供体）内部的纳米颗粒实际释放药物的方法。因此，我们提出了一种使用数值反卷积的新方法，以通过现有透析测试确定的纳米粒子和受体中游离药物溶液的实验释放曲线，评估供体内部纳米粒子的实际药物释放动力学。基于两种不同的数值方法开发了两个计算机程序，即使用规定的威布尔函数或正交多项式作为输入函数的最小二乘准则。前者用于这项工作中的所有分析，而后者则用于验证预测的可靠性。从通过不同透析设置和膜孔径获得的各种纳米颗粒制剂中释放药物的实验数据用于证实该方法。结果表明，该方法适用于广泛的纳米颗粒和微粒制剂，无需其他实验。它与颗粒配方，药物释放机制和测试条件无关。该新方法还可以与现有的透析设备结合使用，以开发用于质量控制，体内外相关性以及开发纳米粒子和其他类型的分散体制剂的标准化方法。