Anti-HIV-1 nanotherapeutics: promises and challenges for the future

Mahajan, Supriya D.; Aalinkeel, Ravikumar; Law, Wing Cheung; Reynolds, Jessica L.; Nair, Bindukumar; Sykes, Donald E.; Yong, Ken‐Tye; Roy, Indrajit; Prasad, Paras N.; Schwartz, Stanley A.

doi:10.2147/ijn.s25871

Cited by 121 publications

(91 citation statements)

References 103 publications

(210 reference statements)

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“…[19][20][21][22][23][24] The potential advantages of using nanoformulations over conventional HIV therapies include the capacity to incorporate, encapsulate, or conjugate a variety of drugs to offer tunable and site-specific targeting and drug release. 25 In addition, the use of nanosystems to deliver a therapeutic molecule can overcome biological barriers; improve drug stability, solubility, and bioavailability; and reduce side effects. [26][27][28] A wide range of nanomaterials have been used and evaluated for their efficiency to deliver HIV-1 therapeutics.…”

Section: Introductionmentioning

confidence: 99%

“…[26][27][28] A wide range of nanomaterials have been used and evaluated for their efficiency to deliver HIV-1 therapeutics. 25,29 Particular interest has been focused on polymeric particles prepared from polyesters such as poly(lacticco-glycolic) acid (PLGA), poly(lactide), and polyglycolide due to their biocompatibility and biodegradability and their approval by the US Food and Drug Administration for use in drug delivery and biomaterial applications. [30][31][32] Various polymeric nanomedicines have been developed for the delivery of antiretroviral drugs in HIV reservoir sites, giving some hope for viral eradication.…”

Section: Introductionmentioning

confidence: 99%

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Preparation, characterization, and safety evaluation of poly(lactide-co-glycolide) nanoparticles for protein delivery into macrophages

Guedj¹,

Kell²,

Barnes³

et al. 2015

IJN

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Following infection, HIV establishes reservoirs within tissues that are inaccessible to optimal levels of antiviral drugs or within cells where HIV lies latent, thus escaping the action of anti-HIV drugs. Macrophages are a persistent reservoir for HIV and may contribute to the rebound viremia observed after antiretroviral treatment is stopped. In this study, we further investigate the potential of poly(lactic- co -glycolic) acid (PLGA)-based nanocarriers as a new strategy to enhance penetration of therapeutic molecules into macrophages. We have prepared stable PLGA nanoparticles (NPs) and evaluated their capacity to transport an active molecule into the human monocyte/macrophage cell line THP-1 using bovine serum albumin (BSA) as a proof-of-concept compound. Intracellular localization of fluorescent BSA molecules encapsulated into PLGA NPs was monitored in live cells using confocal microscopy, and cellular uptake was quantified by flow cytometry. In vitro and in vivo toxicological studies were performed to further determine the safety profile of PLGA NPs including inflammatory effects. The size of the PLGA NPs carrying BSA (PLGA-BSA) in culture medium containing 10% serum was ~126 nm in diameter, and they were negatively charged at their surface (zeta potential =−5.6 mV). Our confocal microscopy studies and flow cytometry data showed that these PLGA-BSA NPs are rapidly and efficiently taken up by THP-1 monocyte-derived macrophages (MDMs) at low doses. We found that PLGA-BSA NPs increased cellular uptake and internalization of the protein in vitro. PLGA NPs were not cytotoxic for THP-1 MDM cells, did not modulate neutrophil apoptosis in vitro, and did not show inflammatory effect in vivo in the murine air pouch model of acute inflammation. In contrast to BSA alone, BSA encapsulated into PLGA NPs increased leukocyte infiltration in vivo, suggesting the in vivo enhanced delivery and protection of the protein by the polymer nanocarrier. We demonstrated that PLGA-based nanopolymer carriers are good candidates to efficiently and safely enhance the transport of active molecules into human MDMs. In addition, we further investigated their inflammatory profile and showed that PLGA NPs have low inflammatory effects in vitro and in vivo. Thus, PLGA nanocarriers are promising as a drug delivery strategy in macrophages for prevention and eradication of intracellular pathogens such as HIV and Mycobacterium tuberculosis .

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preparation, characterization, and safety evaluation of poly(lactide-co-glycolide) nanoparticles for protein delivery into macrophages

Guedj¹,

Kell²,

Barnes³

et al. 2015

IJN

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“…They are very biodegradable polymers where the biologic active agents can be dissolved, entrapped, or encapsulated. Unlike synthetic polymers, the natural polymers widely vary in physical and chemical composition [12,14,76]. Lavimudine loaded chitosan nanoparticle were prepared by ionic gelation of chitosan with tripolyphosphate anion [77].…”

Section: Natural Polymersmentioning

confidence: 99%

“…Moreover, these drugs suffer from physicochemical problems such as poor solubility permeability, and stability which may lead to formulation development problems and impair optimal absorption, biodistribution, and sustained antiretroviral effect. In order to overcome these problems, several new chemical entities or improved delivery systems have been proposed involving the use of several nanotechnology-based delivery systems [10][11][12][13][14]. Thus, in order to improve HIV therapy, a large number of carriers have been developed; they include polymeric nanoparticles, solid lipid nanoparticles, liposomes, nanoemulsions, dendrimers, and drug conjugates [15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Nanotechnology Approaches for Antiretroviral Drugs Delivery

Iannazzo¹,

Pistone²,

Romeo³

et al. 2015

Journal of AIDS and HIV infections

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The development of effective drug delivery approaches for the treatment of AIDS and HIV infection is a global challenge. The advent of multidrug, highly active antiretroviral therapy (HAART), have increased the life span of HIV-infected patients. However, it has not eradicated HIV infections, particularly in anatomically privileged sites, such as the brain, testes, gut, liver, kidney, and secondary lymphoid tissue. Several nanocarriers have been investigated in order to enhance the effective delivery of antiretroviral drugs for HIV prevention and therapy. This review focuses on the most recent and significant examples of nanotechnology-based approaches for the delivery of antiretroviral agents belonging to the classes of nucleoside-analog reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). Nanocarriers such as natural and synthetic polymeric nanoparticles, dendrimers, liposomes, and various drug conjugates have been discussed. These nanotechnology carriers are able to deliver the antiretroviral agents in a controlled and/or targeted manner thereby increasing the drug bioavailability and residence time at target sites with a considerable improvement in quality of HIV patients.

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“…It will be of no surprise if the detection limits, sensitivity and specificity, costing and turnaround time of all molecular assays are improved in the near future, with the introduction of new ideas such as UDS and nanoparticle assays [126]. Amplicon sequencing will allow researchers to identify individual viral mutants that were previously undetected in population sequencing.…”

Section: Future Perspectivementioning

confidence: 99%

Current Assays for HIV-1 Diagnostics and Antiretroviral Therapy Monitoring: Challenges and Possibilities

Chen

Yam

2013

Future Virol.

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In 2011, there were over 34 million people living with HIV infections, placing a heavy burden on public health sectors. HIV infection is a lifelong threat that cannot be prevented by vaccination or cured by antiretroviral drugs. The infected patients rely on daily antiretroviral therapy to suppress HIV viral replication. Hence, it is important to diagnose HIV infections as early as possible and to monitor the efficacy of antiretroviral therapy every 3–6 months. Different immunoassays detecting HIV antigens and antibodies have been modified to offer better sensitivity and more rapid diagnosis. Several clinical and virological parameters, including CD4+ cell counts, viral load and drug resistance mutations, are also used for treatment monitoring. Many molecular assay optimizations are now being utilized to improve patient care. This review will focus on the most updated HIV diagnostic assays, as well as discussing the upcoming possibilities of other advanced technologies.

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Anti-HIV-1 nanotherapeutics: promises and challenges for the future

Cited by 121 publications

References 103 publications

Preparation, characterization, and safety evaluation of poly(lactide-co-glycolide) nanoparticles for protein delivery into macrophages

Preparation, characterization, and safety evaluation of poly(lactide-co-glycolide) nanoparticles for protein delivery into macrophages

Nanotechnology Approaches for Antiretroviral Drugs Delivery

Current Assays for HIV-1 Diagnostics and Antiretroviral Therapy Monitoring: Challenges and Possibilities

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