Noninvasive characterization of the effect of varying PLGA molecular weight blends on in situ forming implant behavior using ultrasound imaging.
Noninvasive characterization of the effect of varying PLGA molecular weight blends on in situ forming implant behavior using ultrasound imaging.
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DOI：
10.7150/thno.4181
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发表时间：
2012
期刊：
影响因子：
12.4
通讯作者：
Exner AA
中科院分区：
文献类型：
--
作者：
Solorio L;Olear AM;Hamilton JI;Patel RB;Beiswenger AC;Wallace JE;Zhou H;Exner AA
原位成型植入物(ISFI)由于其简单的制造和微创给药而在药物输送应用中显示出良好的前景。精确、可重复地控制ISFIs的药物释放是其成功临床应用的关键。研究了不同相对分子质量的聚(D，L-乳酸-乙醇酸共聚)聚合物在体内外不同摩尔比对小分子模拟药物荧光素钠释放的影响。将三种不同的PLGA分子量(15、29和53 kDa)以及每个PLGA分子量与1-甲基-2-吡咯烷酮(NMP)的三种1：1摩尔比组合与模拟药物荧光素溶解，制成植入物。由于种植体在ISFI形成和降解过程中的形态和微观结构是种植体性能的关键决定因素，而且相转化速度已被证明对种植体微观结构有影响，因此诊断超声被用来无创性地量化两种环境中相转化的程度和膨胀行为。植入物的侵蚀、降解以及体外和体内释放情况也使用标准技术进行了测量。使用非线性数学模型将药物释放行为与聚合物相转化相关联，所有处方的R2值都大于0.95。超声波也被用来在12天内对植入物进行3D图像重建。在这项研究中，溶胀和相变与聚合物的相对分子质量呈负相关，53 kDa的聚合物植入物的平均增长速度为9.4%/天，而15 kDa的PLGA为18.6%/天。此外，对于53 kDa的植入物，开始侵蚀、完全反相和降解促进释放需要9d，而对于15 kDa的植入物，这些相同的过程在注入PBS后3d开始。还观察到，与纯聚合物配方相比，PLGA共混物通常具有中等性能。然而，共混制剂的释放曲线受一套更复杂的过程控制，而不仅仅是纯聚合物制剂的释放曲线的平均。这项研究表明，通过改变仓库配方中使用的聚合物的摩尔比，可以定制植入物的性能，如反相、溶胀和药物释放。
In situ forming implants (ISFIs) have shown promise in drug delivery applications due to their simple manufacturing and minimally invasive administration. Precise, reproducible control of drug release from ISFIs is essential to their successful clinical application. This study investigated the effect of varying the molar ratio of different molecular weight (Mw) poly(D,L-lactic-co-glycolic acid) (PLGA) polymers within a single implant on the release of a small Mw mock drug (sodium fluorescein) both in vitro and in vivo. Implants were formulated by dissolving three different PLGA Mw (15, 29, and 53kDa), as well as three 1:1 molar ratio combinations of each PLGA Mw in 1-methyl-2-pyrrolidinone (NMP) with the mock drug fluorescein. Since implant morphology and microstructure during ISFI formation and degradation is a crucial determinant of implant performance, and the rate of phase inversion has been shown to have an effect on the implant microstructure, diagnostic ultrasound was used to noninvasively quantify the extent of phase inversion and swelling behavior in both environments. Implant erosion, degradation, as well as the in vitro and in vivo release profiles were also measured using standard techniques. A non-linear mathematical model was used to correlate the drug release behavior with polymer phase inversion, with all formulations yielding an R2 value greater than 0.95. Ultrasound was also used to create a 3D image reconstruction of an implant over a 12 day span. In this study, swelling and phase inversion were shown to be inversely related to the polymer Mw with 53kDa polymer implants increasing at an average rate of 9.4%/day compared with 18.6%/day in the case of the 15 kDa PLGA. Additionally the onset of erosion, complete phase inversion, and degradation facilitated release required 9 d for 53 kDa implants, while these same processes began 3 d after injection into PBS with the 15 kDa implants. It was also observed that PLGA blends generally had intermediate properties when compared to pure polymer formulations. However, release profiles from the blend formulations were governed by a more complex set of processes and were not simply averages of release profiles from the pure polymers preparations. This study demonstrated that implant properties such as phase inversion, swelling and drug release could be tailored to by altering the molar ratio of the polymers used in the depot formulation.
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影响因子：
3.4
作者：
Bakhshi, Raheleh;Vasheghani-Farahani, Ebrahim;Khakpour, Mazyar
通讯作者：
Khakpour, Mazyar
影响因子：
10.8
作者：
DesNoyer, JR;McHugh, AJ
通讯作者：
McHugh, AJ
DOI：
10.1016/j.ejpb.2009.06.008
发表时间：
2010-01-01
影响因子：
4.9
作者：
Kempe, Sabine;Metz, Hendrik;Maeder, Karsten
通讯作者：
Maeder, Karsten
影响因子：
3.7
作者：
Eliaz, RE;Wallach, D;Kost, J
通讯作者：
Kost, J
影响因子：
10.8
作者：
Graham, PD;Brodbeck, KJ;McHugh, AJ
通讯作者：
McHugh, AJ