Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Glycoconj J. 2010 May;27(4):445-59. doi: 10.1007/s10719-010-9292-3. Epub 2010 May 11.
Carbohydrates are attractive candidates for drug development because sugars are involved in many, if not most, complex human diseases including cancer, immune dysfunction, congenital disorders, and infectious diseases. Unfortunately, potential therapeutic benefits of sugar-based drugs are offset by poor pharmacologic properties that include rapid serum clearance, poor cellular uptake, and relatively high concentrations required for efficacy. To address these issues, pilot studies are reported here where 'Bu(4)ManNAc', a short chain fatty acid-monosaccharide hybrid molecule with anti-cancer activities, was encapsulated in polyethylene glycol-sebacic acid (PEG-SA) polymers. Sustained release of biologically active compound was achieved for over a week from drug-laden polymer formulated into microparticles thus offering a dramatic improvement over the twice daily administration currently used for in vivo studies. In a second strategy, a tributanoylated ManNAc analog (3,4,6-O-Bu(3)ManNAc) with anti-cancer activities was covalently linked to PEG-SA and formulated into nanoparticles suitable for drug delivery; once again release of biologically active compound was demonstrated.
碳水化合物是药物开发的有吸引力的候选物，因为糖参与许多复杂的人类疾病，即使不是大多数，包括癌症、免疫功能障碍、先天疾病和传染病。不幸的是，基于糖的药物的潜在治疗益处被较差的药理性质所抵消，这些性质包括快速血清清除、细胞摄取不良以及为了达到疗效所需的相对较高浓度。为了解决这些问题，本研究报告了将具有抗癌活性的短链脂肪酸-单糖杂合分子“Bu(4)ManNAc”包封在聚乙二醇-癸二酸（PEG-SA）聚合物中的初步研究。载药聚合物制成微球后可实现生物活性化合物的持续释放超过一周，从而大大改善了目前用于体内研究的每日两次给药方式。在第二种策略中，具有抗癌活性的三丁酸甘露糖类似物（3,4,6-O-Bu(3)ManNAc）与 PEG-SA 共价连接并制成适合药物递送的纳米颗粒；再次证明了生物活性化合物的释放。
