Stealth anti-CD4 conjugated immunoliposomes with dual antiretroviral drugs – Modern Trojan horses to combat HIV

Ramana, Lakshmi Narashimhan; Sharma, Shilpee; Sethuraman, Swaminathan; Ranga, Udaykumar; Krishnan, Uma Maheswari

doi:10.1016/j.ejpb.2014.11.021

Cited by 44 publications

(28 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ramana et al . developed anti-CD4 modified liposomes loaded with nevirapine and saquinavir and evaluated them for cellular uptake and antiretroviral responses in Jurkat T cell lines [50]. The liposomes were prepared by thin film hydration and covalently linked to anti-CD4 antibody via thiol-maleimide chemistry.…”

Section: Targeted Deliverymentioning

confidence: 99%

“…To such ends, short palindromic repeat (CRISPR)-associated protein-9 nuclease (Cas9) systems were developed for HIV-1 proviral excision in order to eliminate latent provirus [87, 88]. The means to deliver this cargo to lymphoid tissues such as GALT and lymph nodes as well as the CNS and specifically to CD4+ T cells and macrophages is being sought [49, 50, 53, 59]. Certainly the needs to develop novel polymer and medicinal chemistry approaches for optimal manufacture of receptor-targeted nanoformulated Cas9 is of utmost importance and inevitably to use such approaches to efficiency use such formulations in reducing provirus DNA in infected cell reservoirs of virus.…”

Section: Excision and Elimination Of Hiv Proviral Dnamentioning

confidence: 99%

See 1 more Smart Citation

Long-acting slow effective release antiretroviral therapy

Edagwa

McMillan

Sillman

et al. 2017

Expert Opinion on Drug Delivery

View full text Add to dashboard Cite

Introduction 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. Areas covered 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. Expert opinion 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.

show abstract

Section: Targeted Deliverymentioning

confidence: 99%

Section: Excision and Elimination Of Hiv Proviral Dnamentioning

confidence: 99%

Long-acting slow effective release antiretroviral therapy

Edagwa

McMillan

Sillman

et al. 2017

Expert Opinion on Drug Delivery

View full text Add to dashboard Cite

show abstract

“…Over 100 publications, most focused on particular types of cancer cells, show that targeted immunoliposomes improve the cell-type specificity of drug delivery and reduce toxicity. Therapeutic drug loaded immunoliposomes include those targeting cells expressing the VEGF-Receptors-2 and −3 (24), the oxytocin receptor(25), the epidermal growth factor receptor, EGFR (26), CD4 (27), and HER2 (28, 29). The active delivery of immunoliposomes generally improves cell-type specificity and drug effectiveness by 3- to 10-fold (25, 30, 31) over passive delivery.…”

Section: Introductionmentioning

confidence: 99%

Targeted antifungal liposomes

Ambati

Ferarro

Khang

et al. 2019

Preprint

View full text Add to dashboard Cite

15 Aspergillus species cause pulmonary invasive aspergillosis resulting in nearly a hundred 16 thousand deaths each year. Patients at the greatest risk of developing life-threatening 17 aspergillosis have weakened immune systems and/or various lung disorders. Patients are 18 treated with antifungals such as amphotericin B (AmB), casofungin acetate, or triazoles 19 (itraconazole, voriconazole etc.), but these antifungal agents have serious limitations due to lack 20 of sufficient fungicidal effect and human toxicity. Liposomes with AmB intercalated into the lipid 21 membrane (AmBisomes, AmB-LLs), have several-fold reduced toxicity compared to detergent 22 Importance 41 The fungus Aspergillus fumigatus causes pulmonary invasive aspergillosis resulting in 42 nearly a hundred thousand deaths each year. Patients are often treated with antifungal drugs 43 such as amphotericin B loaded into liposomes, AmB-LLs, but all antifungal drugs including 44 AmB-LLs have serious limitations due to human toxicity and insufficient fungal cell killing. Even 45with the best current therapies, one-year survival among patients with invasive aspergillosis is 46 only 25 to 60%. Hence, there is a critical need for improved antifungal therapeutics. 47Dectin-1 is a mammalian protein that binds to beta-glucan polysaccharides found in 48 nearly all fungal cell walls. We coated AmB-LLs with Dectin-1 to make DEC-AmB-LLs. DEC-49

show abstract

“…The hypothesized delivery mechanism involved the interaction of the nanoformulation with membrane CD4, followed by its endocytosis, and pH-dependent endosomal escape of indinavir into the cell cytoplasm, where it inhibits the viral protease [70]. Very recently, a stealth anti-CD4-targeted immunoliposome loaded with saquinavir and nevirapine has been developed which demonstrated an efficient uptake of the drugs into CD4+ Jurkat T cells and an enhanced anti-viral efficacy at significantly lower concentrations when compared to the free drug [71]. Kovochich and colleagues designed lipid nanoparticles loaded with bryostatin-2, a protein kinase C activator able to activate latent HIV-1 infections.…”

Section: Nano-delivery Of Arvs To the Cellular Sanctuariesmentioning

confidence: 99%

“…In this context, the most studied sanctuary [71] saquinavir nevirapine CD4+ Jurkat T cells lipid NP-bryostatin-2 [72] nelfinavir CD4+ T-cells and in vivo model glycine/mannose-PPI [73] efavirenz monocytes/macrophages tuftsin-PPI [74] efavirenz macrophages mannose-PPI [75] lamivudine macrophages…”

Section: Central Nervous Systemmentioning

confidence: 99%

Antiretroviral Therapy through Barriers: A Prominent Role for Nanotechnology in HIV-1 Eradication from Sanctuaries

Corsi¹,

Sorrentino²,

Mazzucchelli³

et al. 2016

JPP

View full text Add to dashboard Cite

Abstract:In HIV-1 management, eradication of the virus from sanctuaries represents a major and challenging goal. The genital tract, gut associated lymphoid tissue, lymph nodes, central nervous system, macrophages and latently infected CD4+ T lymphocytes are typical sites where HIV-1 compartmentalizes. To circumvent this problem, a consistent number of studies have focused on improving ARVs (antiretroviral drugs) delivery into sanctuary sites and different nanotechnological approaches have been developed. Cellular HIV-1 sanctuaries (i.e. macrophages) can be reached by nanoformulation of ARVs or by activation of latently infected cells. Anatomical sanctuaries (i.e. brain or male genital tract) can be addressed by increasing the permeation of ARVs across tissue barriers, such as the blood-brain barrier or the blood-testis barrier, while ARVs concentration in lymph nodes can be enhanced by drug encapsulation in CD4-targeted nanoparticles.

show abstract

Stealth anti-CD4 conjugated immunoliposomes with dual antiretroviral drugs – Modern Trojan horses to combat HIV

Cited by 44 publications

References 61 publications

Long-acting slow effective release antiretroviral therapy

Long-acting slow effective release antiretroviral therapy

Targeted antifungal liposomes

Antiretroviral Therapy through Barriers: A Prominent Role for Nanotechnology in HIV-1 Eradication from Sanctuaries

Contact Info

Product

Resources

About