Effect of injection site on in situ implant formation and drug release in vivo.
Effect of injection site on in situ implant formation and drug release in vivo.
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DOI：
10.1016/j.jconrel.2010.08.020
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发表时间：
2010-11-01
期刊：
影响因子：
--
通讯作者：
Exner AA
中科院分区：
文献类型：
--
作者：
Patel RB;Solorio L;Wu H;Krupka T;Exner AA
原位形成的药物递送植入物由于其递送易碎药物的能力、简单的制造过程和较少侵入性的放置而提供了用于局部药物递送的预成型植入装置的有吸引力的替代方案。然而，这些系统的临床转化受到阻碍，部分原因是体外和体内药物释放曲线之间的相关性差。为了更好地理解这种效应，在皮下注射以及注射到坏死、非坏死和消融肿瘤中后，在体外和体内检查了聚（D，l-丙交酯-共-乙交酯）（PLGA）原位形成植入物的行为。使用超声成像技术对植入物形成进行非侵入性定量。药物释放的模型药物剂，荧光素，在不同的环境中与相转化。结果表明，对于所有植入物制剂，体内突释药物大于体外。在不同的体内环境中，药物从植入物中释放最快的是消融肿瘤，其次是植入物在非坏死肿瘤，皮下组织，最后在坏死肿瘤组织中，分别在0.7，0.9，9.7和12.7小时释放50%的载药质量。在更硬的消融和非坏死肿瘤组织中的植入物显示出比在更顺应性的皮下和坏死肿瘤环境中的植入物更快的药物释放。最后，使用超声检查的植入物形成证实，在体内沉淀过程（相转化）与药物释放成正比。这些研究结果表明，不仅是药物释放依赖于植入物的形成，但外部环境的影响，如组织的机械性能，可以解释在体内和体外药物释放从原位形成植入物之间的差异。
In situ forming drug delivery implants offer an attractive alternative to pre-formed implant devices for local drug delivery due to their ability to deliver fragile drugs, simple manufacturing process, and less invasive placement. However, the clinical translation of these systems has been hampered, in part, by poor correlation between in vitro and in vivo drug release profiles. To better understand this effect, the behavior of poly(D,l-lactide-co-glycolide) (PLGA) in situ forming implants was examined in vitro and in vivo after subcutaneous injection as well as injection into necrotic, non-necrotic, and ablated tumor. Implant formation was quantified noninvasively using an ultrasound imaging technique. Drug release of a model drug agent, fluorescein, was correlated with phase inversion in different environments. Results demonstrated that burst drug release in vivo was greater than in vitro for all implant formulations. Drug release from implants in varying in vivo environments was fastest in ablated tumor followed by implants in non-necrotic tumor, in subcutaneous tissue, and finally in necrotic tumor tissue with 50% of the loading drug mass released in 0.7, 0.9, 9.7, and 12.7 h respectively. Implants in stiffer ablated and non-necrotic tumor tissue showed much faster drug release than implants in more compliant subcutaneous and necrotic tumor environments. Finally, implant formation examined using ultrasound confirmed that in vivo the process of precipitation (phase inversion) was directly proportional to drug release. These findings suggest that not only is drug release dependent on implant formation but that external environmental effects, such as tissue mechanical properties, may explain the differences seen between in vivo and in vitro drug release from in situ forming implants.
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影响因子：
10.8
作者：
Solorio, Luis;Babin, Brett M.;Patel, Ravi B.;Mach, Justyna;Azar, Nami;Exner, Agata A.
通讯作者：
Exner, Agata A.
DOI：
10.1016/j.ejpb.2008.07.008
发表时间：
2008-11-01
影响因子：
4.9
作者：
Ahmed, Abid Riaz;Dashevsky, Andrei;Bodmeier, Roland
通讯作者：
Bodmeier, Roland
影响因子：
10.8
作者：
DesNoyer, JR;McHugh, AJ
通讯作者：
McHugh, AJ
影响因子：
4.9
作者：
Patel, Ravi B.;Carlson, Angela N.;Solorio, Luis;Exner, Agata A.
通讯作者：
Exner, Agata A.
影响因子：
10.8
作者：
Exner, AA;Krupka, TM;Teets, JM
通讯作者：
Teets, JM