Fix J A
ALZA Corporation, Palo Alto, California 94303, USA.
J Pharm Sci. 1996 Dec;85(12):1282-5. doi: 10.1021/js960158a.
The development of oral formulations for the effective delivery of peptides and proteins has been an elusive target. Although some success has been achieved (e.g., with cyclosporine), progress has been slow compared with what has been achieved with more traditional, organic drug molecules. Poor membrane permeability, enzymatic instability, and large molecular size are three factors that have remained major hurdles for peptide formulators. Absorption-enhancing agents that have been effective, at least in research environments, with smaller drug candidates, have also shown some limited efficacy in small animal models with certain peptides. In most cases, however, effective formulations have only achieved fairly low peptide absorption (< 10%) and have also resulted in significant alterations in the normal cellular morphology of the gastrointestinal tract, at least on a transient basis. Both literature and current data are reviewed in this report. Taken as a whole, the data suggest that the successful development of oral peptide formulations remains a significant challenge. Where successes are achieved, they will most likely be on a case-by-case basis and will reflect a balance between absorption-promoting efficacy of the formulation and the extent to which transient alteration of cell or tissue morphology occurs.
开发用于有效递送肽和蛋白质的口服制剂一直是一个难以实现的目标。尽管已经取得了一些成功（例如环孢素），但与更传统的有机药物分子相比，进展仍然缓慢。膜通透性差、酶不稳定性和分子量大是肽配方设计师仍然面临的三个主要障碍。至少在研究环境中对较小候选药物有效的吸收增强剂，在某些肽的小动物模型中也显示出有限的疗效。然而，在大多数情况下，有效的制剂仅实现了相当低的肽吸收（<10%），并且至少在短暂的基础上还导致了胃肠道正常细胞形态的显著改变。本报告对文献和当前数据进行了综述。总体而言，数据表明口服肽制剂的成功开发仍然是一项重大挑战。在取得成功的情况下，很可能是逐案实现的，并且将反映制剂的吸收促进功效与细胞或组织形态的短暂改变程度之间的平衡。
