Therapeutic efficacies of nano carriers and dissolution kinetics

B. Krueger, Taylor L Frazier, Sheila Galbreath, Tarun Goswami
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Abstract

The drug dissolution behavior of poorly soluble medication such as doxorubicin has been conducted in this paper. Since the drug was fixed, different carriers used to deliver it and their dissolutions kinetics compiled from literature evaluated in this paper. Even though targeting of drugs is very important in drug delivery, it is not within the scope of this paper. However, functionalization of the carrier may provide this benefit, those constructs are included for comparison in terms of hybrid constructs. Dendrimer, micelles and hybrid constructs used in the delivery of doxorubicin compared in this paper with respect to carrier size and drug loading. Assuming that the dissolution follows a slow release, 40-50% of the drug in the phase I representing the sudden or the burst release, followed by a steady release of 50-60% of the drug in phase II, not all the carriers and their sizes exhibited this behavior. Carriers and hybrid constructs 38nm size were more effective where phase I and II was observed, however, as the size decreased to 34 nm or increased, dissolution kinetics with minimal release occurred meaning the carriers were too big to penetrate the vasculature permeability. Nano-carriers, dendrimers, micelle, hybrid dendrimers, and hybrid micelle were found to be effective with the carrier manufacturing, generation, polymer, molecular weight of the carrier and other parameters. The release rate of doxorubicin was found to be effective with dendrimers together with hybrid dendrimer exhibiting a bilinear kinetics. Micelles 20nm were more effective representing 60% of release in 10 hours followed by additional 25% in 35 hours exhibiting a bilinear behavior. Size greater than 20nm resulted in slow dissolution reaching less than 10 to 40% of drug. Several drugs exhibited multiple slopes in their dissolution kinetics when micelle was used. The therapeutic efficacy of hybrid micelle was superior to other nano-carriers.
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纳米载体的治疗效果及溶出动力学
本文对阿霉素等难溶性药物的溶出行为进行了研究。由于药物是固定的,因此本文根据文献评价整理了不同的载体及其溶解动力学。尽管药物靶向在药物传递中非常重要,但它不在本文的讨论范围之内。然而,载体的功能化可以提供这种好处,这些结构被包括在混合结构方面进行比较。树状大分子、胶束和混合结构体用于阿霉素的递送,在载体大小和药物负载方面进行了比较。假设溶出遵循缓慢释放,即在I期有40-50%的药物突然或爆发性释放,然后在II期有50-60%的药物稳定释放,但并非所有的载体及其大小都表现出这种行为。在第一阶段和第二阶段中,38nm大小的载体和杂交构建体更有效,然而,当尺寸减小到34 nm或增加时,溶解动力学发生最小释放,这意味着载体太大而无法穿透血管通透性。研究发现,纳米载体、枝状大分子、胶束、杂化枝状大分子和杂化胶束对载体的制备、生成、聚合物、载体的分子量等参数均有影响。多柔比星对树状大分子和杂化树状大分子的释放率均有效,表现为双线性动力学。20nm胶束更有效,在10小时内释放60%,随后在35小时内释放25%,表现出双线性行为。粒径大于20nm导致缓慢溶出,溶出度小于药物的10% ~ 40%。使用胶束时,几种药物的溶解动力学表现出多重斜率。杂化胶束的治疗效果优于其他纳米载体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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