Long-Acting Efavirenz and HIV-1 Fusion Inhibitor Peptide Co-loaded Polymer–Lipid Hybrid Nanoparticles: Statistical Optimization, Cellular Uptake, and <i>In Vivo</i> Biodistribution

Surve, Dhanashree H.; Jirwankar, Yugandhara B; Dighe, Vikas; Jindal, Anil

doi:10.1021/acs.molpharmaceut.0c00773

Cited by 16 publications

(6 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The dosage form was able to deliver the antiviral payload to infected sites like lymph nodes and the reproductive tract for 5 days. Interestingly, the nanoparticles also permeated the blood-brain barrier and the results were promising to employ nanoformulations for LA delivery in human use [144]. For the delivery of a synergistic two-drug ARV combination consisting of a pre-clinical NNRTI, Compound 55, and NRTI, 4 -ethynyl-2-fluoro-2 -deoxyadenosine (EFdA), Beelor et al developed two LA-ART interventions, one an injectable nano-formulation and the other based on pharmacokinetics and antiviral activity in a hu-mouse model of HIV infection.…”

Section: Formulationmentioning

confidence: 95%

“…Nevertheless, many NNRTI's as LA formulations are still in the developmental stage with Cabenuva being approved recently and can be expected in the next decade (Table 1). Preclinical Subcutaneous [144] Drug adherence to multiple drugs is essential to prevent relapse, and hence the dosage regimen by extending dosing intervals by LA formulation may lead to a successful therapeutical approach. Recently, ViiV Healthcare and Janssen Pharmaceuticals (Janssen) developed a dosing kit containing separate injectable suspensions of Cabotegravir and RPV for intramuscular (IM) use (Table 2).…”

Section: Formulationmentioning

confidence: 99%

See 1 more Smart Citation

Strategies in the Design and Development of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Vanangamudi,

Palaniappan,

Kathiravan

et al. 2023

Viruses

View full text Add to dashboard Cite

AIDS (acquired immunodeficiency syndrome) is a potentially life-threatening infectious disease caused by human immunodeficiency virus (HIV). To date, thousands of people have lost their lives annually due to HIV infection, and it continues to be a big public health issue globally. Since the discovery of the first drug, Zidovudine (AZT), a nucleoside reverse transcriptase inhibitor (NRTI), to date, 30 drugs have been approved by the FDA, primarily targeting reverse transcriptase, integrase, and/or protease enzymes. The majority of these drugs target the catalytic and allosteric sites of the HIV enzyme reverse transcriptase. Compared to the NRTI family of drugs, the diverse chemical class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) has special anti-HIV activity with high specificity and low toxicity. However, current clinical usage of NRTI and NNRTI drugs has limited therapeutic value due to their adverse drug reactions and the emergence of multidrug-resistant (MDR) strains. To overcome drug resistance and efficacy issues, combination therapy is widely prescribed for HIV patients. Combination antiretroviral therapy (cART) includes more than one antiretroviral agent targeting two or more enzymes in the life cycle of the virus. Medicinal chemistry researchers apply different optimization strategies including structure- and fragment-based drug design, prodrug approach, scaffold hopping, molecular/fragment hybridization, bioisosterism, high-throughput screening, covalent-binding, targeting highly hydrophobic channel, targeting dual site, and multi-target-directed ligand to identify and develop novel NNRTIs with high antiviral activity against wild-type (WT) and mutant strains. The formulation experts design various delivery systems with single or combination therapies and long-acting regimens of NNRTIs to improve pharmacokinetic profiles and provide sustained therapeutic effects.

show abstract

Section: Formulationmentioning

confidence: 95%

Section: Formulationmentioning

confidence: 99%

Strategies in the Design and Development of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Vanangamudi,

Palaniappan,

Kathiravan

et al. 2023

Viruses

View full text Add to dashboard Cite

show abstract

“…Clearly, the extent of therapeutic drug penetration into crucial niches within the GI tract requires further study, as it is critical that any cure option be efficacious in targeting intestinal viral reservoirs. It is encouraging, therefore, that contemporary drug design has focused on ensuring tissue penetration, often including the GI tract, of ARVs and that great strides have been made in ensuring tissue biodistribution [41][42][43].…”

Section: The Gastrointestinal Tract: An Important Compartment For Hiv...mentioning

confidence: 99%

Eliminating HIV reservoirs for a cure: the issue is in the tissue

Busman‐Sahay

Starke

Nekorchuk

et al. 2021

Current Opinion in HIV and AIDS

View full text Add to dashboard Cite

Purpose of reviewAdvances in antiretroviral therapy have saved numerous lives, converting a diagnosis with human immunodeficiency virus 1 (HIV-1) from a death sentence into the possibility for a (nearly) normal life in many instances. However, the obligation for lifelong adherence, increased risk of accumulated co-morbidities, and continued lack of uniform availability around the globe underscores the need for an HIV cure. Safe and scalable HIV cure strategies remain elusive, in large part due to the presence of viral reservoirs in which caches of infected cells remain hidden from immune elimination, primarily within tissues. Herein, we summarize some of the most exciting recent advances focused on understanding, quantifying, and ultimately targeting HIV tissue viral reservoirs.Recent findingsCurrent studies have underscored the differences between viral reservoirs in tissue compartments as compared to peripheral blood, in particular, the gastrointestinal (GI) tract. Additionally, several novel or modified techniques are showing promise in targeting the latent viral reservoir, including modifications in drug delivery platforms and techniques such as CRISPR.SummaryElimination of tissue viral reservoirs is likely the key to generation of an effective HIV cure. Exciting studies have come out recently that reveal crucial insights into topics ranging from the basic biology of reservoir seeding to effective drug targeting. However, there are still many outstanding questions in the field about the relative importance of specific reservoirs, such as the GI tract, that may alter the final strategy pursued.

show abstract

“…A great variety of works are investigating new means and bioengineering techniques to deliver drugs to infected cells and/or present immunogens to immune cells in specific compartments, which could lead to enhanced efficiency of natural immune responses [ 181 , 182 , 183 , 184 , 185 , 186 ]. Pino et al demonstrated in SIV-infected RM that administration of FTY720 (fingolimod), a drug used to treat multiple sclerosis, limits viral persistence by increasing the number of cytolytic cells in the LN, a critical site for HIV/SIV replication and persistence [ 187 ].…”

Section: Evaluation Of Hiv Cure Strategies With the Help Of Nhp Modelsmentioning

confidence: 99%

Interests of the Non-Human Primate Models for HIV Cure Research

et al. 2021

View full text Add to dashboard Cite

Non-human primate (NHP) models are important for vaccine development and also contribute to HIV cure research. Although none of the animal models are perfect, NHPs enable the exploration of important questions about tissue viral reservoirs and the development of intervention strategies. In this review, we describe recent advances in the use of these models for HIV cure research and highlight the progress that has been made as well as limitations using these models. The main NHP models used are (i) the macaque, in which simian immunodeficiency virus (SIVmac) infection displays similar replication profiles as to HIV in humans, and (ii) the macaque infected by a recombinant virus (SHIV) consisting of SIVmac expressing the HIV envelope gene serving for studies analyzing the impact of anti-HIV Env broadly neutralizing antibodies. Lessons for HIV cure that can be learned from studying the natural host of SIV are also presented here. An overview of the most promising and less well explored HIV cure strategies tested in NHP models will be given.

show abstract

Long-Acting Efavirenz and HIV-1 Fusion Inhibitor Peptide Co-loaded Polymer–Lipid Hybrid Nanoparticles: Statistical Optimization, Cellular Uptake, and In Vivo Biodistribution

Cited by 16 publications

References 62 publications

Strategies in the Design and Development of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Strategies in the Design and Development of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Eliminating HIV reservoirs for a cure: the issue is in the tissue

Interests of the Non-Human Primate Models for HIV Cure Research

Contact Info

Product

Resources

About