Multi-organ targeting of HIV-1 viral reservoirs with etravirine loaded nanostructured lipid carrier: An in-vivo proof of concept

Rojekar, Satish; Abadi, Leila Fotooh; Pai, Rohan; Mahajan, Ketan; Kulkarni, Smita; Vavia, Pradeep R.

doi:10.1016/j.ejps.2021.105916

Cited by 23 publications

(14 citation statements)

References 108 publications

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“…For example, liposomes have been documented as capable to increase half-lives of d4T, AZT, ddI and RTV [13][14][15][16]20,79,80] (Table 3). Finally, many ART have a limited bioavailability in the brain, but the ability of lipid nanocarriers to mediate the brain delivery of ARVs has been widely documented, either for liposomes that potentially improve brain accumulation of AZT [81], or for SLN used for improving brain bioavailability of ATV, SQV, EFV, NVP and DRV [64,65,[82][83][84][85], or NLC used as carriers of LPV, ATV, ETR [83,86,87] and NE improving brain accumulation of SQV and IDV [88][89][90]. From these studies it is worthwhile highlighting the SLN developed for EFV delivery that attained 150 folds more brain targeting delivery than the free drug [84]; the NLC for ATV delivery that attained 2.75 folds higher Cmax at brain and 4 folds higher brain bioavailability [86] and NE as carrier of IDV that assured specific brain accumulation of the drug [89] (tables 3 to 5).…”

Section: Lipid Emulsions Nanoemulsion O/w Snedds W/o/wmentioning

confidence: 99%

“…Aside from extending the circulation time of nanocarriers, it is also critical to use targeting strategies that can deliver ARV drugs to sites of latent HIV reservoirs such as lymph nodes, the spleen, and the gut mucosa, where HIV-target cells such as memory CD4+ T cells, macrophages, microglia, and astrocytes in the CNS are prevalent [148]. Some of these targeting strategies include: (i) surface functionalization of nanocarriers with sugar molecules like mannose [13,102] or galactose [14,15,99] that are recognized by lectin receptors found on the surface of cells from the mononuclear phagocyte system (MPS); (ii) coating of nanocarriers with hydrophilic molecules (e.g., aminoacids, glucose) to facilitate BBB permeation by carrier mediated transcytosis [55]; (iii) engineering of the lipid matrix of the nanocarriers (SLN, NLC, nanoemulsions) in order to mimic low density lipoproteins (LDL) that are recognized by LDL receptors, thus facilitating BBB permeation by receptor mediated transcytosis [54,55,64,65,85,87,89,90,128]; (iv) functionalization with ligands (e.g., HSA and monoclonal antibody (mAb)) that enhance BBB permeation by receptor mediated transcytosis [65,128]; (v) inhibition of Pgp, which increases brain specific accumulation [89]; and (vi) magnetic aided transport across BBB [121] and to MPS cells [122].…”

Section: Tuning the Physicochemical Properties Of Lipid-based Nanocarriers To Overcome Biological Barriersmentioning

confidence: 99%

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Lipid Nanocarriers for Anti-HIV Therapeutics: a Focus on Physicochemical Properties and Biotechnological Advances

Faria¹,

Lopes²,

Neves³

et al. 2021

Preprint

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Since HIV was first identified, and in a relatively short period of time, AIDS has become one of the most devastating infectious diseases of the 21st century. Classical antiretroviral therapies were a major step forward in disease treatment options, significantly improving the survival rates of HIV-infected individuals. Even though these therapies have greatly improved HIV clinical outcomes, antiretrovirals (ARV) feature biopharmaceutic and pharmacokinetic problems such as poor aqueous solubility, short half-life and poor penetration into HIV reservoir sites, which contribute to the sub-optimal efficacy of these regimens. To overcome some of these issues, novel nanotechnology-based strategies for ARV delivery towards HIV viral reservoirs have been proposed. The current review focus on the benefits of using lipid-based nanocarriers for tuning the physicochemical properties of ARVs to overcome biological barriers upon administration. Furthermore, a correlation of these properties and the potential therapeutic outcomes has been established. Biotechnological advancements using lipid nanocarriers for RNA interference delivery for the treatment of HIV infections were also discussed.

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Section: Lipid Emulsions Nanoemulsion O/w Snedds W/o/wmentioning

confidence: 99%

Section: Tuning the Physicochemical Properties Of Lipid-based Nanocarriers To Overcome Biological Barriersmentioning

confidence: 99%

Lipid Nanocarriers for Anti-HIV Therapeutics: a Focus on Physicochemical Properties and Biotechnological Advances

Faria¹,

Lopes²,

Neves³

et al. 2021

Preprint

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show abstract

“…UNAIDS Global update-2023 revealed the declining mortality rate from AIDS and the number of HIV infections existing (38.5 million), bringing HIV infection closer to achieving sustainable development goal 3.3 towards eliminating AIDS as a public health issue by 2030 [2]. HIV usually forms sanctuaries in various body organs, including the brain, spleen, liver, kidney, lung, and lymph nodes, that infect immune cells to cause weak immunity [3]. Conversely, cellular systems such as macrophages [4] and CD4+…”

Section: Introductionmentioning

confidence: 99%

“…Despite the availability of highly active antiretroviral therapy (HAART), only partial immune system improvement was reported with HAART [8]. Thus, increasing the dose of ARDs would be the only practical solution which causes higher dose-induced adverse effects to have been reported as a concern for the treatment of HIV infection [3]. The situation is more complicated for BCS II and IV drugs, as they undergo extensive hepatic metabolism and efflux by the P-gp pump, which can cause low oral bioavailability and poor drug biodistribution throughout the organs [9].…”

Section: Introductionmentioning

confidence: 99%

Fabrication of TPGS decorated Etravirine loaded lipid nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targeting

Muheem,

Wasim,

Aldosari

et al. 2023

Preprint

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Etravirine (ERVN) is a potential NNRTI (non-nucleoside reverse transcriptase inhibitor) in treating HIV infection. It possesses extremely low oral bioavailability. The present research aims to optimize the formulation and characterization of TPGS-enriched ERVN-loaded lipid-based nanocarriers (LNCs) for HIV-infected patients. The formulation, ERVN-TPGS-LNCs, was optimized by CCRD using a modified-solvent evaporation process. Various characterization parameters of LNCs were evaluated, including globule size of 121.56 ± 2.174 nm, PDI of 0.172 ± 0.042, the zeta potential of -7.32 ± 0.021 mV, %EE of 94.42 ± 8.65% of ETR and %DL was 8.94 ± 0.759% of ERVN and spherical shape was revealed by TEM. PXRD was also performed to identify the crystallinity of the sample. In-vitro drug release showed % a cumulative drug release of 79.77 ± 8.35% at pH 1.2 and 83.23 ± 9.11% at pH 6.8, respectively, at the end of 48h compared to pure drug suspension (ERVN-S). Further, the intestinal permeation study and confocal microscope showed approximately ~3-fold and ~2-fold increased permeation in ERVN-TPGS-LNCs and ERVN-LNCs across the gut sac compared to ERVN-S. Hemolysis compatibility and lipolysis studies were performed to predict the in-vivo fate of the formulation. The pharmacokinetic study revealed a 3.13-fold increment in the relative bioavailability, which agrees with the ex-vivo studies, and lymphatic uptake was validated by using cycloheximide (CYHD) along with designed formulation, which leads to lowering AUC of ERVN-TPGS-LNCs. Thus, this study ensures that ERVN-TPGS-LNCs take lymphatic uptake to minimize the first-pass metabolism followed by improved oral bioavailability of EVN. Thus, the enhanced bioavailability of ERVN can reduce the high dose of ERVN to minimize the adverse effects related to dose-related burden.

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“…HIV infection, commonly referred to as acquired immune deficiency syndrome (AIDS), is one of the utmost challenging diseases of the 21st century, with severe social, financial, and political implications in developed and developing nations [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. As it is an immunological disorder, it weakens the immune system, thereby increasing the risk of death due to opportunistic comorbidities, such as tuberculosis, septicemia, and pneumonia [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Nanotechnology-Based Approaches for Targeting HIV Reservoirs

et al. 2022

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Highly active anti-retroviral therapy (HAART) is prescribed for HIV infection and, to a certain extent, limits the infection’s spread. However, it cannot completely eradicate the latent virus in remote and cellular reservoir areas, and due to the complex nature of the infection, the total eradication of HIV is difficult to achieve. Furthermore, monotherapy and multiple therapies are not of much help. Hence, there is a dire need for novel drug delivery strategies that may improve efficacy, decrease side effects, reduce dosing frequency, and improve patient adherence to therapy. Such a novel strategy could help to target the reservoir sites and eradicate HIV from different biological sanctuaries. In the current review, we have described HIV pathogenesis, the mechanism of HIV replication, and different biological reservoir sites to better understand the underlying mechanisms of HIV spread. Further, the review deliberates on the challenges faced by the current conventional drug delivery systems and introduces some novel drug delivery strategies that have been explored to overcome conventional drug delivery limitations. In addition, the review also summarizes several nanotechnology-based approaches that are being explored to resolve the challenges of HIV treatment by the virtue of delivering a variety of anti-HIV agents, either as combination therapies or by actively targeting HIV reservoir sites.

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Multi-organ targeting of HIV-1 viral reservoirs with etravirine loaded nanostructured lipid carrier: An in-vivo proof of concept

Cited by 23 publications

References 108 publications

Lipid Nanocarriers for Anti-HIV Therapeutics: a Focus on Physicochemical Properties and Biotechnological Advances

Lipid Nanocarriers for Anti-HIV Therapeutics: a Focus on Physicochemical Properties and Biotechnological Advances

Fabrication of TPGS decorated Etravirine loaded lipid nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targeting

Novel Nanotechnology-Based Approaches for Targeting HIV Reservoirs

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