Characterization of formulation parameters affecting low molecular weight drug release from in situ forming drug delivery systems.
Characterization of formulation parameters affecting low molecular weight drug release from in situ forming drug delivery systems.
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DOI：
10.1002/jbm.a.32724
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发表时间：
2010-08
影响因子：
4.9
通讯作者：
Exner, Agata A.
中科院分区：
文献类型：
--
作者：
Patel, Ravi B.;Carlson, Angela N.;Solorio, Luis;Exner, Agata A.
关键词：
原位形成植入物（ISFI）已显示出在微创癌症治疗（如肿瘤热消融）后提供辅助化疗的前景。虽然ISFI系统已经被彻底研究用于递送高分子量（Mw）治疗剂，但是很少进行研究来优化其用于递送低Mw药物的设计。本研究检查了不同制剂组分对ISFI中低分子量药物释放曲线的影响，ISFI由聚（D，L-丙交酯-共-乙交酯）、荧光素（模型药物）和溶于1-甲基-2-吡咯烷酮（NMP）的赋形剂组成。研究了不同PLGA分子量、赋形剂浓度和载药量的影响。此外，进行溶解度研究以确定相转化所需的临界水浓度。结果表明，PLGA分子量是调节低分子量药物从ISFI系统释放的最重要因素。与较高Mw PLGA（60 kDa）55.1 ± 3.1%相比，由低Mw（16 kDa）PLGA组成的ISFI制剂显示出显著（p<0.05）较低的突释（24小时后）28.2 ± 0.5%。临界水浓度研究还表明，具有较低Mw PLGA的制剂在水中的溶解度增加，因此可能需要更多的时间来相转化和释放药物。
In situ forming implants (ISFI) have shown promise in delivering adjuvant chemotherapy following minimally invasive cancer therapies such as thermal ablation of tumors. While ISFI systems have been thoroughly investigated for delivery of high molecular weight (Mw) therapeutics, little research has been conducted to optimize their design for delivery of low Mw drugs. This study examined the effect of varying the formulation components on the low Mw drug release profile from a ISFI consisting of poly(D,L-lactide-co-glycolide), fluorescein (model drug), and excipient dissolved in 1-methyl-2-pyrrolidinone (NMP). Effects of varying PLGA Mw, excipient concentration, and drug loading were studied. Additionally, solubility studies were conducted to determine the critical water concentration required for phase inversion. Results demonstrated that PLGA Mw was the most significant factor in modulating low Mw drug release from the ISFI systems. ISFI formulations comprised of a low Mw (16 kDa) PLGA showed a significantly (p<0.05) lower burst release (after 24 hours), 28.2 ± 0.5%, compared to higher Mw PLGA (60 kDa), 55.1 ± 3.1%. Critical water concentration studies also demonstrated that formulations with lower Mw PLGA had increased solubility in water and may thus require more time to phase invert and release the drug.
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影响因子：
10.8
作者：
Luan, XS;Bodmeier, R
通讯作者：
Bodmeier, R
影响因子：
4.9
作者：
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通讯作者：
Gao, Jinming
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10.8
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DesNoyer, JR;McHugh, AJ
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McHugh, AJ
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Ravivarapu, HB;Moyer, KL;Dunn, RL
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Dunn, RL
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作者：
Brem, H;Gabikian, P
通讯作者：
Gabikian, P