Noninvasive characterization of in situ forming implants using diagnostic ultrasound.
Noninvasive characterization of in situ forming implants using diagnostic ultrasound.
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DOI：
10.1016/j.jconrel.2010.01.001
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发表时间：
2010-04-19
影响因子：
10.8
通讯作者：
Exner, Agata A.
中科院分区：
文献类型：
--
作者：
Solorio, Luis;Babin, Brett M.;Patel, Ravi B.;Mach, Justyna;Azar, Nami;Exner, Agata A.
原位形成的药物递送系统提供了一种手段，通过该手段，控释贮库可以在不使用手术的情况下物理地插入靶部位。药物从这些系统的释放速率通常与植入物形成的速率有关。目前，只有有限数量的技术可用于监测相转化，并且这些方法都不能用于直接和非侵入性地可视化该过程。在这项研究中，诊断超声被用来可视化和量化的过程中，植入物形成的相转化为基础的系统在体外和体内。同时，使用荧光素钠作为模拟药物来评价药物释放曲线并将药物释放和植入物形成过程相关联。植入物组成的三种不同分子量的聚（乳酸-共-乙醇酸）（PLGA）聚合物溶解在1-甲基-2-吡咯烷酮（NMP）进行了体外研究和29 kDa的PLGA溶液进行了体内评价。将植入物包封在1%琼脂糖组织模型中5天，或皮下注射到大鼠中并评价48小时。使用图像分析技术评价了灰度值（对应于植入物形成速率）、溶胀和沉淀的定量测量，表明聚合物分子量对原位药物递送储库的溶胀和形成具有相当大的影响。在体内释放和贮库形成之间也观察到线性相关性（R2=0.93）。这项研究表明，第一次，超声波可用于非侵入性和非破坏性的监测和评价的相转化过程中原位形成的药物输送植入物，形成过程可以直接相关的药物释放依赖于此形成的初始阶段。
In situ forming drug delivery systems provide a means by which a controlled release depot can be physically inserted into a target site without the use of surgery. The release rate of drugs from these systems is often related to the rate of implant formation. Currently, only a limited number of techniques are available to monitor phase inversion, and none of these methods can be used to visualize the process directly and noninvasively. In this study, diagnostic ultrasound was used to visualize and quantify the process of implant formation in a phase inversion based system both in vitro and in vivo. Concurrently, sodium fluorescein was used as a mock drug to evaluate the drug release profiles and correlate drug release and implant formation processes. Implants comprised of three different molecular weight poly(lactic-co-glycolic acid) (PLGA) polymers dissolved in 1-methyl-2-pyrrolidinone (NMP) were studied in vitro and a 29 kDa PLGA solution was evaluated in vivo. The implants were encapsulated in a 1% agarose tissue phantom for five days, or injected into a rat subcutaneously and evaluated for 48 hrs. Quantitative measurements of the gray-scale value (corresponding to the rate of implant formation), swelling, and precipitation were evaluated using image analysis techniques, showing that polymer molecular weight has a considerable effect on the swelling and formation of the in situ drug delivery depots. A linear correlation was also seen between the in vivo release and depot formation (R2=0.93). This study demonstrates, for the first time, that ultrasound can be used to noninvasively and nondestructively monitor and evaluate the phase inversion process of in situ forming drug delivery implants, and that the formation process can be directly related to the initial phase of drug release dependent on this formation.
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DOI：
10.1002/0471475734.ch12
发表时间：
2005-01-01
期刊：
DRUG DELIVERY: PRINCIPLES AND APPLICATIONS
影响因子：
--
作者：
Ng, Ka-yun;Matsunaga, Terry O.
通讯作者：
Matsunaga, Terry O.
影响因子：
10.8
作者：
Luan, XS;Bodmeier, R
通讯作者：
Bodmeier, R
影响因子：
2.1
作者：
Astaneh, Reyhaneh;Nafissi-Varcheh, Nastaran;Erfan, Mohammad
通讯作者：
Erfan, Mohammad
影响因子：
4.6
作者：
Kranz, H.;Bodmeier, R.
通讯作者：
Bodmeier, R.
影响因子：
10.8
作者：
Raman, C;McHugh, AJ
通讯作者：
McHugh, AJ