Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles.
Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles.
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DOI：
10.1016/j.ijpharm.2016.01.004
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发表时间：
2016-02-29
影响因子：
5.8
通讯作者：
Ainslie KM
中科院分区：
文献类型：
--
作者：
Collier MA;Peine KJ;Gautam S;Oghumu S;Varikuti S;Borteh H;Papenfuss TL;Sataoskar AR;Bachelder EM;Ainslie KM
利什曼病是由利什曼原虫寄生虫引起的一种疾病，在全世界影响近1200万人，并且由于寄生虫对病原体导向疗法的广泛耐药性，与治疗并发症有关。内脏利什曼病（VL）是一种全体性疾病，目前的治疗方法涉及病原体介导的药物，治疗方案时间长，增加了形成耐药菌株的风险。限制耐药病原体出现的一种方法是使用宿主介导的治疗方法。宿主介导的治疗性AR-12已被FDA批准用于癌症治疗，已显示出对广泛的细胞内病原体的活性；然而，由于疏水性和毒性，很难达到治疗剂量。我们使用新型可生物降解聚合物醋酸化葡聚糖（Ace-DEX）将AR-12配制成微粒（AR-12/MPs），并将该配方用于VL的全身治疗。AR-12/MPs治疗可显著降低感染小鼠的肝脏、脾脏和骨髓寄生虫负荷，而两性霉素B联合治疗的效果更为显著。总的来说，AR-12/MPs提供了一种独特的宿主介导的治疗方法，可以显著减少VL治疗中耐药的出现。
Leishmaniasis is a disease caused by parasites of Leishmania sp., which effects nearly 12 million people worldwide and is associated with treatment complications due to widespread parasite resistance toward pathogen-directed therapeutics. The current treatments for visceral leishmaniasis (VL), the systemic form of the disease, involve pathogen-mediated drugs and have long treatment regimens, increasing the risk of forming resistant strains. One way to limit emergence of resistant pathogens is through the use of host-mediated therapeutics. The host-mediated therapeutic AR-12, which is FDA IND-approved for cancer treatment, has shown activity against a broad spectrum of intracellular pathogens; however, due to hydrophobicity and toxicity, it is difficult to reach therapeutic doses. We have formulated AR-12 into microparticles (AR-12/MPs) using the novel biodegradable polymer acetalated dextran (Ace-DEX) and used this formulation for the systemic treatment of VL. Treatment with AR-12/MPs significantly reduced liver, spleen, and bone marrow parasite loads in infected mice, while combinatorial therapies with amphotericin B had an even more significant effect. Overall, AR-12/MPs offer a unique, host-mediated therapy that could significantly reduce the emergence of drug resistance in the treatment of VL.
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影响因子：
3.1
作者：
Guo, Shuliang;Zhao, Jinqiu
通讯作者：
Zhao, Jinqiu
影响因子：
5.5
作者：
Halperin, SA;Dobson, S;Eiden, JJ
通讯作者：
Eiden, JJ
DOI：
10.1073/pnas.0901592106
发表时间：
2009-04-07
影响因子：
11.1
作者：
Broaders, Kyle E.;Cohen, Joel A.;Frechet, Jean M. J.
通讯作者：
Frechet, Jean M. J.
影响因子：
4.9
作者：
Chiu, Hao-Chieh;Kulp, Samuel K.;Chen, Ching-Shih
通讯作者：
Chen, Ching-Shih
影响因子：
4.9
作者：
Bachelder EM;Beaudette TT;Broaders KE;Fréchet JM;Albrecht MT;Mateczun AJ;Ainslie KM;Pesce JT;Keane-Myers AM
通讯作者：
Keane-Myers AM