Recent Publications

The latest research and clinical studies being done in long-acting, extended release drugs for HIV and TB.

Translation of combination nanodrugs into nanomedicines: lessons learned and future outlook

Date: 
1/10/18
Citation: 

Mu Q, Yu J, McConnachie LA Kraft JC, Gao Y, Gulati GK, Ho RJY. Translation of combination nanodrugs into nanomedicines: lessons learned and future outlook. J Drug Target. Jun-Jul 2018;26(5-6):435-447. doi: 10.1080/1061186X.2017.1419363. Epub 2018 Jan 10. PMID: 29285948; PMCID: PMC6205718.

For the past two decades, the number of research publications on single-agent nanoformulations has grown exponentially. However, formulations advancing to pre-clinical and clinical evaluations that lead to therapeutic products has been limited.

Health Topics: 

Indocyanine green nanoparticles undergo selective lymphatic uptake, distribution and retention and enable detailed mapping of lymph vessels, nodes and abnormalities

Date: 
2/12/18
Citation: 

Kraft JC, Treuting PM, Ho RJY. Indocyanine green nanoparticles undergo selective lymphatic uptake, distribution and retention and enable detailed mapping of lymph vessels, nodes and abnormalities. J Drug Target. 2018 Jun-Jul;26(5-6):494-504. doi: 10.1080/1061186X.2018.1433681. Epub 2018 Feb 12. PMID: 29388438 PMCID: PMC6205717

The distributed network of lymph vessels and nodes in the body, with its complex architecture and physiology, presents a major challenge for whole-body lymphatic-targeted drug delivery. To gather physiological and pathological information of the lymphatics, near-infrared (NIR) fluorescence imaging of NIR fluorophores is used in clinical practice due to its tissue-penetrating optical radiation (700-900 nm) that safely provides real-time high-resolution in vivo images. 

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Long-acting profile of 4 drugs in 1 anti-HIV nanosuspension in nonhuman primates for 5 weeks after a single subcutaneous injection

Date: 
7/15/18
Citation: 

McConnachie LA, Kinman LM, Koehn J, et al. Long-acting profile of 4 drugs in 1 anti-HIV nanosuspension in nonhuman primates for 5 weeks after a single subcutaneous injection. J Pharm Sci. 2018 Jul;107(7):1787-1790. doi: 10.1016/j.xphs.2018.03.005. Epub 2018 Mar 13. PMID: 29548975; PMCID: PMC6954863.

Daily oral antiretroviral therapy regimens produce limited drug exposure in tissues where residual HIV persists and suffer from poor patient adherence and disparate drug kinetics, which all negatively impact outcomes. To address this, we developed a tissue- and cell-targeted long-acting 4-in-1 nanosuspension composed of lopinavir (LPV), ritonavir, tenofovir (TFV), and lamivudine (3TC). In 4 macaques dosed subcutaneously, drug levels over 5 weeks in plasma, lymph node mononuclear cells (LNMCs), and peripheral blood mononuclear cells (PBMCs) were analyzed by liquid chromatography-tandem mass spectrometry. 

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Long-acting injectable atovaquone nanomedicines for malaria prophylaxis

Citation: 

Bakshi RP, Tatham LM, Savage AC, et al. Long-acting injectable atovaquone nanomedicines for malaria prophylaxis. Nat Commun. 2018;9(1):315. Published 2018 Jan 22. doi:10.1038/s41467-017-02603-z. PMID: 29358624, PMCID: PMC5778127.

Chemoprophylaxis is currently the best available prevention from malaria, but its efficacy is compromised by non-adherence to medication. Here we develop a long-acting injectable formulation of atovaquone solid drug nanoparticles that confers long-lived prophylaxis against Plasmodium berghei ANKA malaria in C57BL/6 mice. Protection is obtained at plasma concentrations above 200 ng ml-1 and is causal, attributable to drug activity against liver stage parasites

Long-acting formulations for the treatment of latent tuberculous infection: opportunities and challenges

Date: 
2/15/18
Citation: 

Swindells S, Siccardi M, Barrett SE, et al. Long-acting formulations for the treatment of latent tuberculous infection: opportunities and challenges. Int J Tuberc Lung Dis. 2018 Feb 1; 22(2): 125–132. PMID: 29506608; PMCID: PMC6103451.

Long-acting/extended-release drug formulations have proved very successful in diverse areas of medicine, including contraception, psychiatry and, most recently, human immunodeficiency virus (HIV) disease. Though challenging, application of this technology to anti-tuberculosis treatment could have substantial impact. 

Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy

Date: 
1/9/18
Citation: 

Kirtane AR, Abouzid O, Minahan D, et al. Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy. Nat Commun. 2018;9(1):2. Published 2018 Jan 9. doi:10.1038/s41467-017-02294-6. PMID: 29317618; PMCID: PMC5760734.

The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed.

Health Topics: 

From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection

Date: 
12/26/17
Citation: 

Kudalkar SN, Beloor J, Quijano E, et al. From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection [published correction appears in Proc Natl Acad Sci U S A. 2018 Mar 12;:]. Proc Natl Acad Sci U S A. 2018;115(4):E802-E811. doi:10.1073/pnas.1717932115. PMID: 29279368; PMCID: PMC5789948.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) that target the viral polymerase have been a key component of the current HIV-1 combination drug regimens; however, these issues hamper them. Thus, the development of novel more effective NNRTIs as anti-HIV-1 agents with fewer long-term liabilities, efficacy on new drug-resistant HIV-1 strains, and less frequent dosing is crucial.

Health Topics: 

Multimodal imaging approach to examine biodistribution kinetics of Cabotegravir (GSK1265744) long acting parenteral formulation in rat

Date: 
12/28/17
Citation: 

Jucker BM, Alsaid H, Rambo M, et al. Multimodal imaging approach to examine biodistribution kinetics of Cabotegravir (GSK1265744) long acting parenteral formulation in rat. J Control Release. 2017;268:102-112. doi:10.1016/j.jconrel.2017.10.017. PMID: 29042321.

Long-Acting Parenterals (LAPs) have been used in the clinic to provide sustained therapeutic drug levels at a target site, and thereby reducing the frequency of dosing required. In an effort to understand the factors associated with long-acting cabotegravir (GSK1265744 LAP) pharmacokinetic variability, the current study was designed to investigate the temporal relationship between intramuscular (IM) or subcutaneous (SC) drug depot morphology and distribution kinetics with plasma pharmacokinetics.

Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles

Date: 
1/15/18
Citation: 

Zhou T, Su H, Dash P, et al. Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles. Biomaterials. 2018;151:53-65. doi:10.1016/j.biomaterials.2017.10.023. PMID: 29059541; PMCID: PMC5926202.

Long-acting parenteral (LAP) antiretroviral drugs have generated considerable interest for treatment and prevention of HIV-1 infection. One new LAP is cabotegravir (CAB), a highly potent integrase inhibitor, with a half-life of up to 54 days, allowing for every other month parenteral administrations. Despite this excellent profile, high volume dosing, injection site reactions and low body fluid drug concentrations affect broad use for virus infected and susceptible people.

Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection

Date: 
5/15/16
Citation: 

Walensky RP, Jacobsen MM, Bekker LG, et al. Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection. J Infect Dis. 2016;213(10):1523-1531. doi:10.1093/infdis/jiv523. PMID: 26681778; PMCID: PMC4837902.

For young South African women at risk for human immunodeficiency virus (HIV) infection, preexposure prophylaxis (PrEP) is one of the few effective prevention options available. Long-acting injectable PrEP, which is in development, may be associated with greater adherence, compared with that for existing standard oral PrEP formulations, but its likely clinical benefits and additional costs are unknown.

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