Lee Hye J
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Kwanak-Gu, Korea.
Arch Pharm Res. 2002 Oct;25(5):572-84. doi: 10.1007/BF02976925.
Rapid development in molecular biology and recent advancement in recombinant technology increase identification and commercialization of potential protein drugs. Traditional forms of administrations for the peptide and protein drugs often rely on their parenteral injection, since the bioavailability of these therapeutic agents is poor when administered nonparenterally. Tremendous efforts by numerous investigators in the world have been put to improve protein formulations and as a result, a few successful formulations have been developed including sustained-release human growth hormone. For a promising protein delivery technology, efficacy and safety are the first requirement to meet. However, these systems still require periodic injection and increase the incidence of patient compliance. The development of an oral dosage form that improves the absorption of peptide and especially protein drugs is the most desirable formulation but one of the greatest challenges in the pharmaceutical field. The major barriers to developing oral formulations for peptides and proteins are metabolic enzymes and impermeable mucosal tissues in the intestine. Furthermore, chemical and conformational instability of protein drugs is not a small issue in protein pharmaceuticals. Conventional pharmaceutical approaches to address these barriers, which have been successful with traditional organic drug molecules, have not been effective for peptide and protein formulations. It is likely that effective oral formulations for peptides and proteins will remain highly compound specific. A number of innovative oral drug delivery approaches have been recently developed, including the drug entrapment within small vesicles or their passage through the intestinal paracellular pathway. This review provides a summary of the novel approaches currently in progress in the protein oral delivery followed by factors affecting protein oral absorption.
分子生物学的快速发展以及重组技术的最新进展增加了潜在蛋白质药物的识别和商业化。肽类和蛋白质药物的传统给药形式通常依赖于肠胃外注射，因为这些治疗剂非肠胃外给药时生物利用度较差。世界各地众多研究人员付出了巨大努力来改进蛋白质制剂，结果开发出了一些成功的制剂，包括缓释人生长激素。对于一种有前景的蛋白质递送技术而言，疗效和安全性是首先要满足的要求。然而，这些系统仍然需要定期注射，并且增加了患者依从性的发生率。开发一种能提高肽类尤其是蛋白质药物吸收的口服剂型是最理想的制剂，但也是制药领域最大的挑战之一。开发肽类和蛋白质口服制剂的主要障碍是代谢酶和肠道中不可渗透的粘膜组织。此外，蛋白质药物的化学和构象不稳定性在蛋白质药物领域也不是一个小问题。解决这些障碍的传统制药方法，虽然对传统有机药物分子很成功，但对肽类和蛋白质制剂却无效。肽类和蛋白质的有效口服制剂可能仍将高度依赖于化合物的特异性。最近已经开发出了许多创新的口服药物递送方法，包括将药物包裹在小囊泡中或使其通过肠道细胞旁通道。本文综述了目前蛋白质口服递送方面正在进行的新方法以及影响蛋白质口服吸收的因素。
