DEXTRAN PRODRUGS STRUCTURE AND STABILITY IN RELATION TO THERAPEUTIC ACTIVITY
DEXTRAN PRODRUGS STRUCTURE AND STABILITY IN RELATION TO THERAPEUTIC ACTIVITY
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DOI：
10.1016/0169-409x(89)90006-9
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发表时间：
1989-01-01
影响因子：
16.1
通讯作者：
LARSEN C
中科院分区：
文献类型：
--
作者：
LARSEN C
目前对大分子葡聚糖前药领域的贡献试图回顾此类聚合物衍生物的化学和物理化学性质对其体内分布和治疗活性的影响。讨论了各种药物固定方法的用途，以提供具有可行的递送特性的明确的葡聚糖-药物缀合物。合成的葡聚糖前药的一些物理化学性质，例如流体动力学体积、形状、柔韧性、电荷和亲水/亲脂平衡，是其药代动力学命运的决定因素。回顾了受这些因素中的一种或多种影响的事件，包括肝脏摄取、RES系统的摄取、外渗和淋巴转运、在组织/体腔中局部停留时间以及肾脏消除。需要强调的是，在生物学评价之前对所制备的葡聚糖前药进行充分表征至关重要。
The present contribution to the field of macromolecular dextran prodrugs attempts to review the influence of the chemical and physicochemical properties of such polymeric derivatives on their in vivo disposition and therapeutic activity. The utility of various drug fixation methods to provide well-defined dextran-drug conjugates with feasible delivery characteristics is discussed. Several physicochemical properties of synthesized dextran prodrugs, such as hydrodynamic volume, shape, flexibility, charge and hydrophilic/lipophilic balance, are determinants for their pharmacokinetic fate. The events influenced by one or more of these factors, including liver uptake, uptake by the RES system, extravasation and lymphatic transport, residence time locally in tissue/body cavity, and renal elimination, are reviewed. It is emphasized that adequate characterization of the prepared dextran prodrugs prior to biological evaluation is of the utmost importance.