Several temporarily stable polymer micelle systems that might be used as ultrasonic-activated drug delivery carriers were synthesized and investigated. These polymeric micelle systems were PlurogelRTM, Tetronic RTM, poly(ethylene oxide)-b-poly(N-isopropylacrylamide) and poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-lactate n).; In previous work in our lab, Pruitt et al. developed a stabilized drug carrier named PlurogelRTM [5, 6]. Unfortunately, the rate of the successful PlurogelRTM synthesis was only about 30% by simply following Pruitt's process. In this work, this rate was improved to 60% by combining the process of adding 0.15 M NaCl and/or 10 mul/ml n-butanol and by preheating the solution before polymerization.; TetronicsRTM were proved not to be good candidates to form temporarily stable polymeric micelle system by polymerizing interpenetrating networks inside their micelle cores. Tetronic micelle systems treated by this process still were not stable at concentrations below their critical micelle concentration (CMC).; Poly(ethylene oxide)-b-poly(N-isopropylacrylamide)-N,N-bis(acryloyl)cystamine micelle-like nanoparticles were developed and characterized. When the N,N-bis(acryloyl)cystamine (BAC) was from 0.2 wt% to 0.75 wt% of the mass of poly(N-isopropylacrylamide), diameters of the nanoparticles at 40°C were less than 150 nm. The cores of the nanoparticles were hydrophobic enough to sequester 1,6-diphenylhexatriene (DPH) and the anti-cancer drug doxorubicin (DOX). Nanoparticles with 0.5 wt% BAC stored at room temperature in 0.002 mg/ml solutions were stable for up to two weeks.; Poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-lactate n) micelle systems were synthesized and characterized. The degree of polymerization of lactate side group, n, was 3 or 5. The copolymers with N-isopropylacrylamide:2-hydroxyethyl methacrylate-lactate3: poly(ethylene oxide) (NIPAAm:HEMA-lactate 3:PEO) ratios of 20.0:5.0:1 or 22.5:2.5:1 and with NIPAAm:HEMA-lactate 5:PEO ratios of 17.5:7.5:1, 20.0:5.0:1 or 22.5:2.5:1 produced micelles stable about 2 days at 40°C. The cores of the micelles were hydrophobic enough to sequester DPH and DOX. The DOX release from the micelles having molar ratio of NIPAAm:HEMA-lactate3:PEO equal to 20.0:5.0:1 was about 2% at room temperature and 4% at body temperature. This system is a possible candidate for ultrasonically activated drug delivery.
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机译：合成和研究了几种可能用作超声活化药物传递载体的暂时稳定的聚合物胶束系统。这些聚合物胶束系统是PlurogelRTM，Tetronic RTM，聚（环氧乙烷）-b-聚（N-异丙基丙烯酰胺）和聚（环氧乙烷）-b-聚（N-异丙基丙烯酰胺-甲基丙烯酸-2-羟乙酯-乳酸n）。 ;在我们实验室的先前工作中，Pruitt等人。开发了一种稳定的药物载体，称为PlurogelRTM [5，6]。不幸的是，仅遵循Pruitt的方法，成功的PlurogelRTM合成率仅约为30％。在这项工作中，通过结合添加0.15 M NaCl和/或10 mul / ml正丁醇并在聚合前将溶液预热的过程，将该比率提高到60％。事实证明，TetronicsRTM不是通过在胶束核心内部互穿网络聚合形成暂时稳定的聚合物胶束系统的良好候选者。通过该方法处理的Tetronic胶束系统在低于其临界胶束浓度（CMC）的浓度下仍不稳定。聚（环氧乙烷）-b-聚（N-异丙基丙烯酰胺）-N，N-双（丙烯酰基）胱胺类胶束状纳米颗粒得到了开发和表征。当N，N-双（丙烯酰基）胱胺（BAC）为聚（N-异丙基丙烯酰胺）质量的0.2重量％至0.75重量％时，纳米粒子在40℃下的直径小于150nm。纳米粒子的核心具有足够的疏水性，可以隔离1,6-二苯基己三烯（DPH）和抗癌药阿霉素（DOX）。室温下以0.002 mg / ml的溶液保存了0.5％BAC的纳米颗粒，稳定了两周。合成并表征了聚（环氧乙烷）-b-聚（N-异丙基丙烯酰胺-甲基丙烯酸2-羟乙酯-乳酸n）胶束体系。乳酸侧基的聚合度n为3或5。与N-异丙基丙烯酰胺：甲基丙烯酸2-羟乙酯-乳酸3：聚环氧乙烷（NIPAAm：HEMA-乳酸3：PEO）的比率为20.0：5.0 1：1或22.5：2.5：1以及NIPAAm：HEMA-乳酸5：PEO比率为17.5：7.5：1、20.0：5.0：1或22.5：2.5：1产生的胶束在40°C稳定约2天。胶束的核心具有足够的疏水性，可以隔离DPH和DOX。 NIPAAm：HEMA-乳酸酯3：PEO摩尔比等于20.0：5.0：1的胶束释放的DOX在室温下约为2％，在体温下约为4％。该系统是超声激活药物递送的可能候选者。
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