Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Finland.
Curr Drug Metab. 2013 Jan;14(1):28-56.
Although it is acknowledged that the main impediment of orally administered therapeutic agents is their extensive and changeable pre-systemic metabolism, low absorption and instability in harsh environment of the gastrointestinal (GI) tract are also main influential factors, resulting into inadequate and erratic drug bioavailability. To overcome these shortcomings, nanotechnology has offered new promising strategies to prevent and treat a wide variety of diseases by employing different oral drug-carrier structures capable to enhance therapeutic effects and minimize the toxicity of healthy organs or cells. This review, in general, elucidates some considerable features of in vitro oral drug delivery in three different parts. The first one summarizes the main challenges for oral drug delivery and available absorption mechanisms. The second part embodies an in-depth discussion on the role of the intestinal absorption models used to predict permeability, cellular uptake or even toxicity of nanoparticles, resulting into the design of nanocarriers with optimum efficacy for oral delivery. The third section of the literature is devoted, more particularly, to nanocarriers developed for oral absorption in the past few years, including the behavior of nanovehicles upon oral administration with respect to membrane permeability, retention properties and stability, as well as methods which may lengthen residence time in the GI environment or improve drug absorption.
尽管人们承认口服治疗药物的主要障碍是其广泛而多变的前体系统代谢，但在胃肠道（GI）恶劣环境中低吸收率和不稳定性也是主要影响因素，导致药物生物利用度不足和不稳定。为了克服这些缺点，纳米技术通过采用不同的口服药物载体结构，提供了新的有前途的策略，以预防和治疗各种疾病，从而增强治疗效果并最小化健康器官或细胞的毒性。总的来说，本综述在三个不同部分阐述了体外口服药物传递的一些重要特征。第一部分总结了口服药物传递的主要挑战和可用的吸收机制。第二部分深入讨论了用于预测纳米粒子渗透性、细胞摄取甚至毒性的肠道吸收模型的作用，从而设计出具有最佳口服传递效果的纳米载体。文献的第三部分专门讨论了过去几年中开发用于口服吸收的纳米载体，包括纳米载体在口服给药时在膜通透性、保留特性和稳定性方面的行为，以及可以延长在胃肠道环境中停留时间或提高药物吸收的方法。
