CONTROLLED DRUG RELEASE FROM POLY(ORTHO ESTERS)
CONTROLLED DRUG RELEASE FROM POLY(ORTHO ESTERS)
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DOI：
10.1111/j.1749-6632.1985.tb18390.x
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发表时间：
1985-06-21
影响因子：
5.2
通讯作者：
HELLER, J
中科院分区：
文献类型：
--
作者：
HELLER, J
由于受控的全身药物输送的重要性，开发能够以易于调节的速率和可预测的动力学输送多种治疗剂的生物可蚀性植入物具有相当重要的意义。实现这一目标的一种方法是开发一种聚合物基质，药物可以物理分散在其中，并且水解过程被限制在固体装置的外表面。在这样的装置中，对于恒定的聚合物水解速率，药物释放速率与药物负载成正比，并且装置的寿命与装置的物理尺寸成正比。然而，由于药物释放速率与装置的总表面积成正比，因此当装置的物理尺寸因侵蚀而减小时，药物释放速率也会降低。药物释放速率的下降是可以预测和计算的。开发此类系统的一种方法是制备一种聚合物，该聚合物的主链中含有键，这些键在生理 pH 值 7.4 下相对稳定，但随着 pH 值降低而变得逐渐不稳定。然后，可以通过物理掺入聚合物中的赋形剂来控制此类聚合物的侵蚀速率，当与水接触时，赋形剂产生引起所需聚合物水解速率的pH。那么，如果聚合物是高度疏水性的，则只有表层中的赋形剂暴露于水，并且聚合物水解将仅发生在表层中。已经开发出两种聚合物系统来满足这些目标。其中一个系统是聚缩醛，另一个是聚原酸酯。〜本文描述了我们在聚原酸酯合成方面的工作以及使用各种赋形剂来实现物理分散在这些聚合物中的各种治疗剂的受控药物释放。
Because of the importance of controlled systemic drug delivery, the development of bioerodible implants that can deliver a wide variety of therapeutic agents at readily adjustable rates and predictable kinetics is of considerable importance.’One means of achieving this objective is to develop a polymer matrix into which a drug can be physically dispersed and where the hydrolytic process is confined to the outer surface of a solid device. In such a device, for a constant rate of polymer hydrolysis, the rate of drug release is directly proportional to drug loading, and the lifetime of the device is directly proportional to the physical dimensions of the device. However, because the rate of drug release is directly proportional to the total surface area of the device, as the physical dimensions of the device decrease through erosion, the rate of drug release will also decrease. The decrease in the rate of drug release is predictable and can be calculated.’One approach to developing such systems is to prepare a polymer that contains linkages in the polymer backbone that are relatively stable at the physiological pH of 7.4, but become progressively unstable as the pH is lowered. The erosion rate of such polymers can then be controlled by means of excipients physically incorporated into the polymer, which, when in contact with water, produce a pH that induces the desired polymer hydrolysis rate. Then, if the polymer is highly hydrophobic, only the excipient in the surface layers is exposed to water, and polymer hydrolysis will occur only in the surface layers. Two polymer systems have been developed that meet these objectives. One of these systems is a polyacetal’and the other a poly (ortho e~ ter).~ This paper describes our work on poly (ortho ester) synthesis and the use of various excipients to achieve controlled drug release of various therapeutic agents physically dispersed in these polymers.