期刊
EXPERT OPINION ON DRUG DELIVERY
卷 14, 期 11, 页码 1281-1291出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/17425247.2017.1288212
关键词
Antiretroviral therapy; viral reservoirs; long-acting slow effective release; nanoformulated ART; targeted drug delivery; HIV-1 proviral excision; anti-inflammatory activities; neuroprotection; theranostics; prodrugs
资金
- National Institutes of Health [P01 DA028555, R01 NS36126, P01 NS31492, 2R01 NS034239, P01 MH64570, P01 NS43985, P30 MH062261, R01 AG043540]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P30GM103509] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [P01MH064570, P30MH062261] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS036126, P01NS031492, P01NS043985, R01NS034239] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG043540] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [P01DA028555] Funding Source: NIH RePORTER
Introduction: Advances in long-acting antiretroviral therapy (ART) can revolutionize current HIV/AIDS treatments. We coined the term long-acting slow effective release ART' (LASER ART) to highlight the required formulation properties of slow drug dissolution, poor water-solubility, bioavailability, little-to-no off-target toxicities and improved regimen adherence. Drug carrier technologies characterized by high antiretroviral drug (ARV) payloads in a single carrier improve the pharmacokinetic and pharmacodynamic profiles. The surface modifications of ARV carriers target monocyte-macrophages and facilitate drug transport across physiological barriers and to virus-susceptible CD4+T cells. Areas covered: The review highlights developments of reservoir-targeted LASER ART for improved therapeutic outcomes. Such nanoART delivery platforms include decorated multifunctional nano- and micro-particles, prodrugs and polymer conjugates. Therapeutic strategies such as gene-editing technologies boost ART effectiveness. Expert opinion: The persistence of HIV-1 in lymphoid, gut and nervous system reservoirs poses a challenge to viral eradication. Emerging slow-release drug carriers can target intracellular pathogens, activate antiviral immunity, promote genome editing, sustain drug depots and combine therapeutics with image contrast agents, and can meet unmet clinical needs for HIV-infected patients. Such efforts will bring the medicines to reservoir sites and accelerate viral clearance.
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