Long-acting slow effective release antiretroviral therapy.
Long-acting slow effective release antiretroviral therapy.
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DOI：
10.1080/17425247.2017.1288212
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发表时间：
2017-11
影响因子：
6.6
通讯作者：
Gendelman HE
中科院分区：
文献类型：
--
作者：
Edagwa B;McMillan J;Sillman B;Gendelman HE
长效抗逆转录病毒疗法（ART）的发展可以彻底改变目前的艾滋病毒/艾滋病治疗方法。基于药物溶解缓慢、水溶性差、生物利用度高、脱靶全身毒性有限和患者治疗依从性好的特性，我们创造了长期活性缓慢有效释放ART（LASER ART）一词。正在开发以单一载体中的抗逆转录病毒药物（ARV）的高有效载荷为特征的药物载体技术，以改善纳米配制的ART（nanoART）的药代动力学和药效学。此外，用靶向配体对缓释抗逆转录病毒载体进行表面修饰，促进了受体介导的跨越生理屏障的转运，从而改善了治疗结果。本综述强调了目前的水库靶向激光ART输送平台，有可能改善艾滋病毒/艾滋病的治疗结果的发展。这种纳米ART递送平台包括修饰的多功能纳米和微米颗粒、前药和聚合物缀合物。治疗策略，如抗炎和神经保护剂和基于CRISPR/Cas 9的基因编辑技术，影响药物库，提高ART有效性和促进病毒清除进行了讨论。HIV-1在其淋巴、肠道和神经系统储库中的持续存在对病毒根除构成了重大挑战。针对细胞内病原体的有效药物和缓释产品的新兴创新策略，基于免疫的干预措施，基因组编辑技术，维持药物库的化合物以及nanoART和图像造影剂的组合有可能满足艾滋病毒患者未满足的临床需求。这些努力将把药物带到活跃的病毒复制部位，加速病毒清除。
Advances in the development of long acting antiretroviral therapy (ART) can revolutionize current treatments for HIV/AIDS. We have coined the term long active slow effective release ART (LASER ART) based on properties of slow drug dissolution, poor water-solubility, excellent bioavailability, limited off target systemic toxicities, and excellent patient treatment adherence. Drug carrier technologies characterized by high payload of antiretroviral drugs (ARVs) in a single carrier are being developed to improve the pharmacokinetics and pharmacodynamics of the nanoformulated ART (nanoART). Additionally, surface modification of slow release antiretroviral carriers with targeting ligands has facilitated receptor-mediated transport across physiological barriers serves to improve therapeutic outcomes. This review highlights current developments of reservoir targeted LASER ART delivery platforms that have the potential to improve HIV/AIDS therapeutic outcomes. Such nanoART delivery platforms include decorated multifunctional nano- and micro- particles, prodrugs and polymer conjugates. Therapeutic strategies such as anti-inflammatory and neuroprotective agents and CRISPR/Cas 9 based gene-editing technologies that affect drug depots, boost ART effectiveness and facilitate viral clearance are discussed. The persistence of HIV-1 in its lymphoid, gut and nervous system reservoirs poses a major challenge to viral eradication. Emerging innovative strategies for effective medicines and slow release products to target intracellular pathogens, immune based interventions, genome-editing technologies, compounds that sustain drug depots and combinations of nanoART and image contrast agents have the potential to meet the unmet clinical needs of HIV patients. Such efforts will bring the medicines to sites of active viral replication and accelerate viral clearance.
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影响因子：
6.7
作者：
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通讯作者：
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DOI：
10.1097/qai.0000000000000258
发表时间：
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作者：
Balkundi S;Nowacek AS;Veerubhotla RS;Chen H;Martinez-Skinner A;Roy U;Mosley RL;Kanmogne G;Liu X;Kabanov AV;Bronich T;McMillan J;Gendelman HE
通讯作者：
Gendelman HE