Brown Larry R
Epic Therapeutics, Inc., 220 Norwood Park South, Norwood, MA 02062, USA.
Expert Opin Drug Deliv. 2005 Jan;2(1):29-42. doi: 10.1517/17425247.2.1.29.
The discovery of insulin in 1922 marked the beginning of research and development to improve the means of delivering protein therapeutics to patients. From that period forward, investigators have contemplated every possible route of delivery. Their research efforts have followed two basic pathways: one path has focused on non-invasive means of delivering proteins to the body; and the second path has been primarily aimed at increasing the biological half-life of the therapeutic molecules. Thus far, the commercial successes of protein delivery by the nasal, oral and pulmonary routes have been more opportunistic rather than the application of platform technologies applicable to every protein or peptide. In several limited cases, sustained delivery of peptides and proteins has employed the use of polymeric carriers. More successes have been achieved by chemical modification using amino acid substitutions, protein pegylation or glycosylation to improve the pharmacodynamic properties of certain macromolecules. Today, commercial successes for protein and peptide delivery systems remain limited. The needle and syringe remain the primary means of protein delivery. Major hurdles remain in order to overcome the combined natural barriers of drug permeability, drug stability, pharmacokinetics and pharmacodynamics of protein therapeutics.
1922年胰岛素的发现标志着改善向患者递送蛋白质疗法手段的研发工作的开端。从那时起，研究人员考虑了每一种可能的递送途径。他们的研究工作遵循两条基本途径：一条途径专注于将蛋白质非侵入性递送至体内的方法；第二条途径主要致力于延长治疗分子的生物半衰期。到目前为止，通过鼻腔、口服和肺部途径递送蛋白质的商业成功更多是靠机缘巧合，而非适用于每种蛋白质或肽的平台技术的应用。在一些有限的案例中，肽和蛋白质的持续递送采用了聚合物载体。通过使用氨基酸取代、蛋白质聚乙二醇化或糖基化进行化学修饰以改善某些大分子的药效学性质，已经取得了更多成功。如今，蛋白质和肽递送系统的商业成功仍然有限。针头和注射器仍是蛋白质递送的主要手段。为了克服蛋白质疗法在药物通透性、药物稳定性、药代动力学和药效学方面的综合天然屏障，仍然存在重大障碍。
