Development of delivery methods for carbohydrate-based drugs: controlled release of biologically-active short chain fatty acid-hexosamine analogs.
Development of delivery methods for carbohydrate-based drugs: controlled release of biologically-active short chain fatty acid-hexosamine analogs.
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DOI：
10.1007/s10719-010-9292-3
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发表时间：
2010-05
影响因子：
3
通讯作者：
Yarema, Kevin J.
中科院分区：
文献类型：
--
作者：
Aich, Udayanath;Meledeo, M. Adam;Sampathkumar, Srinivasa-Gopalan;Fu, Jie;Jones, Mark B.;Weier, Christopher A.;Chung, Sung Yun;Tang, Benjamin C.;Yang, Ming;Hanes, Justin;Yarema, Kevin J.
碳水化合物是药物开发的有吸引力的候选者，因为糖与许多（如果不是大多数）复杂的人类疾病有关，包括癌症、免疫功能障碍、先天性疾病和传染病。不幸的是，糖基药物的潜在治疗益处被较差的药理学特性所抵消，这些特性包括快速的血清清除、较差的细胞摄取以及功效所需的相对较高的浓度。为了解决这些问题，本文报道了初步研究，其中 Bu4ManNAc（一种具有抗癌活性的短链脂肪酸-单糖杂化分子）被封装在聚乙二醇-癸二酸（PEG-SA）聚合物中。从配制成微粒的负载药物的聚合物中，生物活性化合物的持续释放超过一周，从而比目前用于体内研究的每天两次给药有了显着的改进。第二种策略是，将具有抗癌活性的三丁酰化ManNAc类似物（3,4,6-O-Bu3ManNAc）与PEG-SA共价连接，并配制成适合药物输送的纳米颗粒；再次证明了生物活性化合物的释放。
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 Bu4ManNAc , 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-Bu3ManNAc) 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.
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影响因子：
7.3
作者：
Elmouelhi N;Aich U;Paruchuri VD;Meledeo MA;Campbell CT;Wang JJ;Srinivas R;Khanna HS;Yarema KJ
通讯作者：
Yarema KJ
影响因子：
4.8
作者：
Luchansky, SJ;Yarema, KJ;Bertozzi, CR
通讯作者：
Bertozzi, CR
影响因子：
7.3
作者：
Campbell CT;Aich U;Weier CA;Wang JJ;Choi SS;Wen MM;Maisel K;Sampathkumar SG;Yarema KJ
通讯作者：
Yarema KJ
影响因子：
7.8
作者：
Wang, Zhiyun;Du, Jian;Che, Pao-Lin;Meledeo, M. Adam;Yarema, Kevin J.
通讯作者：
Yarema, Kevin J.
影响因子：
2.9
作者：
Kim, EJ;Jones, MB;Yarema, KJ
通讯作者：
Yarema, KJ