Sinha V R, Trehan Aman
Department of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, 160014 Chandigarh, India.
J Control Release. 2003 Jul 31;90(3):261-80. doi: 10.1016/s0168-3659(03)00194-9.
In a very short time, since their emergence, the field of controlled delivery of proteins has grown immensely. Because of their relatively large size, they have low transdermal bioavailabilities. Oral bioavailability is generally poor since they are poorly absorbed and easily degraded by proteolytic enzymes in the gastrointestinal tract. Ocular and nasal delivery is also unfavorable due to degradation by enzymes present in eye tissues and nasal mucosa. Thus parenteral delivery is currently most demanding and suitable for delivery of such molecules. In systemic delivery of proteins, biodegradable microspheres as parenteral depot formulation occupy an important place because of several aspects like protection of sensitive proteins from degradation, prolonged or modified release, pulsatile release patterns. The main objective in developing controlled release protein injectables is avoidance of regular invasive doses which in turn provide patient compliance, comfort as well as control over blood levels. This review presents the outstanding contributions in field of biodegradable microspheres as protein delivery systems, their methods of preparation, drug release, stability, interaction with immune system and regulatory considerations.
在极短的时间内，自其出现以来，蛋白质控释领域取得了巨大的发展。由于它们相对较大的尺寸，其经皮生物利用度较低。口服生物利用度通常较差，因为它们吸收不良且易被胃肠道中的蛋白水解酶降解。眼部和鼻腔给药也不理想，因为眼组织和鼻粘膜中存在的酶会导致降解。因此，目前肠胃外给药对这类分子的递送最为迫切且合适。在蛋白质的全身递送中，可生物降解微球作为肠胃外长效制剂由于在多个方面具有优势，如保护敏感蛋白质不被降解、延长或改变释放、脉冲释放模式等，占据重要地位。开发控释蛋白质注射剂的主要目标是避免常规的侵入性给药剂量，这反过来又能提高患者的依从性、舒适度以及对血液水平的控制。本综述介绍了可生物降解微球作为蛋白质递送系统领域的杰出贡献、其制备方法、药物释放、稳定性、与免疫系统的相互作用以及监管方面的考虑因素。
