González-Fernández Felipe M, Bianchera Annalisa, Gasco Paolo, Nicoli Sara, Pescina Silvia
Department of Food and Drug, University of Parma, Viale Parco Area delle Scienze, 27/a, 43124 Parma, Italy.
Nanovector S.r.l., Via Livorno, 60, 10144 Torino, Italy.
Pharmaceutics. 2021 Mar 26;13(4):447. doi: 10.3390/pharmaceutics13040447.
Nanotherapeutics based on biocompatible lipid matrices allow for enhanced solubility of poorly soluble compounds in the treatment of ophthalmic diseases, overcoming the anatomical and physiological barriers present in the eye, which, despite the ease of access, remains strongly protected. Micro-/nanoemulsions, solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) combine liquid and/or solid lipids with surfactants, improving drug stability and ocular bioavailability. Current research and development approaches based on try-and-error methodologies are unable to easily fine-tune nanoparticle populations in order to overcome the numerous constraints of ocular administration routes, which is believed to hamper easy approval from regulatory agencies for these systems. The predictable quality and specifications of the product can be achieved through quality-by-design (QbD) implementation in both research and industrial environments, in contrast to the current quality-by-testing (QbT) framework. Mathematical modelling of the expected final nanoparticle characteristics by variation of operator-controllable variables of the process can be achieved through adequate statistical design-of-experiments (DoE) application. This multivariate approach allows for optimisation of drug delivery platforms, reducing research costs and time, while maximising the understanding of the production process. This review aims to highlight the latest efforts in implementing the design of experiments to produce optimised lipid-based nanocarriers intended for ophthalmic administration. A useful background and an overview of the different possible approaches are presented, serving as a starting point to introduce the design of experiments in current nanoparticle research.
基于生物相容性脂质基质的纳米疗法可提高难溶性化合物在眼科疾病治疗中的溶解度，克服眼部存在的解剖学和生理学屏障，尽管眼部易于触及，但仍受到严密保护。微乳液/纳米乳液、固体脂质纳米粒（SLN）或纳米结构脂质载体（NLC）将液体和/或固体脂质与表面活性剂结合，提高了药物稳定性和眼部生物利用度。当前基于试错法的研发方法无法轻松微调纳米颗粒群体，以克服眼部给药途径的诸多限制，据信这阻碍了监管机构对这些系统的轻松批准。与当前的测试质量（QbT）框架相反，通过在研究和工业环境中实施设计质量（QbD），可以实现产品可预测的质量和规格。通过充分应用统计实验设计（DoE），可以通过改变过程中操作员可控变量来对预期的最终纳米颗粒特性进行数学建模。这种多变量方法能够优化药物递送平台，降低研究成本和时间，同时最大程度地加深对生产过程的理解。本综述旨在突出在实施实验设计以生产用于眼部给药的优化脂质基纳米载体方面的最新努力。介绍了有用的背景知识和不同可能方法的概述，作为在当前纳米颗粒研究中引入实验设计的起点。
