Solid Lipid Nanoparticles Enhance the Delivery of the HIV Protease Inhibitor, Atazanavir, by a Human Brain Endothelial Cell Line

Chattopadhyay, Niladri; Zastre, Jason; Wong, Ho-Lun; Wu, Xiao Yu; Bendayan, Reina

doi:10.1007/s11095-008-9615-2

Cited by 176 publications

(91 citation statements)

References 47 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…40 In vitro studies also showed increased endothelial uptake of solid lipid ATV and transferrin-tagged saquinavir nanoparticles compared with nontagged drugs. 41,42 The current study shows localization of nanoART in endothelial cell vesicles, suggesting that vesicular transport may be involved in nanoART uptake and trafficking in HBMEC. Future investigations will explore the types of vesicles involved and the molecular mechanisms through which endothelial cells uptake nanoART during endothelial-MP communication.…”

Section: Discussionmentioning

confidence: 58%

Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell-targeted nanoformulated antiretroviral drugs to human brain endothelial cells

Kanmogne¹,

Singh²,

Roy³

et al. 2012

IJN

View full text Add to dashboard Cite

Despite the successes of antiretroviral therapy (ART), HIV-associated neurocognitive disorders remain prevalent in infected people. This is due, in part, to incomplete ART penetration across the blood-brain barrier (BBB) and lymph nodes and to the establishment of viral sanctuaries within the central nervous system. In efforts to improve ART delivery, our laboratories developed a macrophage-carriage system for nanoformulated crystalline ART (nanoART) (atazanavir, ritonavir, indinavir, and efavirenz). We demonstrate that nanoART transfer from mononuclear phagocytes (MP) to human brain microvascular endothelial cells (HBMEC) can be realized through cell-to-cell contacts, which can facilitate drug passage across the BBB. Coculturing of donor MP containing nanoART with recipient HBMEC facilitates intercellular particle transfer. NanoART uptake was observed in up to 52% of HBMEC with limited cytotoxicity. Folate coating of nanoART increased MP to HBMEC particle transfer by up to 77%. To translate the cell assays into relevant animal models of disease, ritonavir and atazanavir nanoformulations were injected into HIV-1-infected NOD/scid-γ c null mice reconstituted with human peripheral blood lymphocytes. Atazanavir and ritonavir levels in brains of mice treated with folate-coated nanoART were three-to four-fold higher than in mice treated with noncoated particles. This was associated with decreased viral load in the spleen and brain, and diminished brain CD11b-associated glial activation. We postulate that monocyte-macrophage transfer of nanoART to brain endothelial cells could facilitate drug entry into the brain.

show abstract

Section: Discussionmentioning

confidence: 58%

Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell-targeted nanoformulated antiretroviral drugs to human brain endothelial cells

Kanmogne¹,

Singh²,

Roy³

et al. 2012

IJN

View full text Add to dashboard Cite

show abstract

“…SLNs may carry both lipophilic and hydrophilic elements. Many substances have been delivered into the brain using SLNs, including camptothecin (RTI International, NC, USA), 165 piperine, 166 docetaxel, 167 small interfering RNA, 168 curcumin, 169 quercetin, 170 idebenone, 171 antiviral agents, 172,173 apomorphine, 174 risperidone, 175 and quinine. 176 Recent reviews have discussed the controversies and benefits of SLNs as carriers of drugs to the brain.…”

Section: Solid Nanoparticlesmentioning

confidence: 99%

Nanoscale drug delivery systems and the blood–brain barrier

Alyautdin¹,

Khalin²,

Nafeeza³

et al. 2014

IJN

121

View full text Add to dashboard Cite

The protective properties of the blood–brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain’s vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual’s age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS.

show abstract

“…Although preliminary, the ability of these NLCs to promote intracellular trafficking at a representative cell line of the BBB suggests that these nanocarriers may be a promising system to enhance zidovudine brain uptake. In another study, atazanavir was loaded into stearic acid-based SLNs for enhanced brain delivery by Chattopadhyay et al 92 SLNs produced by a thin-film hydration technique based on a microemulsion possessed negative charges (zeta potential of approximately −18 mV) and a mean particle-size range between 150 and 250 nm. Besides confirming the low toxicity ppotential of SLNs in hCMEC/ D 3 cell line, a human brain microvessel endothelial cell line (HBMEC), up to a concentration corresponding to 200 nM of atazanavir, this group also demonstrated significantly higher drug-permeation ratios through endothelial cell monolayers compared to atazanavir in aqueous solution after 2 hours of incubation.…”

Section: Antiretroviral Drug-loaded Nanoparticles For Cns Deliverymentioning

confidence: 99%

Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system

Gomes

Neves

2014

IJN

View full text Add to dashboard Cite

Antiretroviral drug therapy plays a cornerstone role in the treatment of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients. Despite obvious advances over the past 3 decades, new approaches toward improved management of infected individuals are still required. Drug distribution to the central nervous system (CNS) is required in order to limit and control viral infection, but the presence of natural barrier structures, in particular the blood–brain barrier, strongly limits the perfusion of anti-HIV compounds into this anatomical site. Nanotechnology-based approaches may help providing solutions for antiretroviral drug delivery to the CNS by potentially prolonging systemic drug circulation, increasing the crossing and reducing the efflux of active compounds at the blood–brain barrier, and providing cell/tissue-targeting and intracellular drug delivery. After an initial overview on the basic features of HIV infection of the CNS and barriers to active compound delivery to this anatomical site, this review focuses on recent strategies based on antiretroviral drug-loaded solid nanoparticles and drug nanosuspensions for the potential management of HIV infection of the CNS.

show abstract

Solid Lipid Nanoparticles Enhance the Delivery of the HIV Protease Inhibitor, Atazanavir, by a Human Brain Endothelial Cell Line

Abstract: These data suggest that SLNs could be a promising drug delivery system to enhance brain uptake of atazanavir and potentially other PIs.

Cited by 176 publications

References 47 publications

Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell-targeted nanoformulated antiretroviral drugs to human brain endothelial cells

Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell-targeted nanoformulated antiretroviral drugs to human brain endothelial cells

Nanoscale drug delivery systems and the blood–brain barrier

Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system

Contact Info

Product

Resources

About

Solid Lipid Nanoparticles Enhance the Delivery of the HIV Protease Inhibitor, Atazanavir, by a Human Brain Endothelial Cell Line

Abstract: These data suggest that SLNs could be a promising drug delivery system to enhance brain uptake of atazanavir and potentially other PIs.

Cited by 176 publications

References 47 publications

Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell-targeted nanoformulated antiretroviral drugs to human brain endothelial cells

Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell-targeted nanoformulated antiretroviral drugs to human brain endothelial cells

Nanoscale drug delivery systems and the blood&ndash;brain barrier

Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system

Contact Info

Product

Resources

About

Nanoscale drug delivery systems and the blood–brain barrier