Yu J, Chien Y W
Controlled Drug-Delivery Research Center, Rutgers University, College of Pharmacy, Piscataway, NJ 08854-8067, USA.
Crit Rev Ther Drug Carrier Syst. 1997;14(4):395-453.
Peptide and protein drugs are being used increasingly in major research and development programs in the pharmaceutical industry and are also an important class of therapeutic agents due to advances in genetic engineering and biotechnology. Systemic delivery of these macromolecular drugs, however, has been limited to the parenteral route largely because of their extensive presystemic elimination when taken orally. Faced with this dilemma concerning the systemic delivery of these macromolecules with their unique conformational complexity for therapeutic activity, pharmaceutical scientists have evaluated the potential of various non-oral routes of administration as alternatives. Despite the tremendous efforts that have been devoted to this problem, only limited success has been achieved--mostly with small peptides. Growing attention has been given to the potential of a pulmonary route as an alternative non-invasive means for systemic delivery of peptide/protein-based therapeutic agents due to the fact that the lung provides a huge but extremely thin absorptive mucosal membrane. Although current studies show great promise, pulmonary delivery of therapeutic peptides and proteins is complicated by the complexity of the anatomic structure of the human respiratory system and the influence on drug deposition exerted by respiration. This review discusses the fundamental structure and physiology of the human respiratory system, current methodology used to study pulmonary drug absorption, approaches of drug delivery to the distal lung, and recent progress in pulmonary drug delivery by case studies. The mechanisms of pulmonary drug absorption are also discussed.
肽类和蛋白质类药物在制药行业的主要研发项目中应用越来越广泛，并且由于基因工程和生物技术的进步，它们也是一类重要的治疗药物。然而，这些大分子药物的全身给药一直局限于肠胃外途径，主要是因为口服时它们会在体循环前被大量消除。面对这些具有独特构象复杂性以发挥治疗活性的大分子全身给药的困境，药物科学家评估了各种非口服给药途径作为替代方法的潜力。尽管在这个问题上付出了巨大努力，但仅取得了有限的成功——主要是针对小肽。由于肺提供了巨大但极其薄的吸收性粘膜，肺部给药途径作为肽/蛋白质类治疗药物全身给药的一种替代非侵入性手段的潜力受到越来越多的关注。尽管目前的研究显示出很大的前景，但治疗性肽和蛋白质的肺部给药因人类呼吸系统解剖结构的复杂性以及呼吸对药物沉积的影响而变得复杂。本综述通过案例研究讨论了人类呼吸系统的基本结构和生理学、目前用于研究肺部药物吸收的方法、药物递送至远端肺的途径以及肺部药物递送的最新进展。还讨论了肺部药物吸收的机制。
