Recent Publications

Be informed about the latest research and clinical studies being done in long-acting, extended release drugs for HIV and TB.

Ultra-long-acting removable drug delivery system for HIV treatment and prevention

Date: 
Nov 12, 2018
Author(s): 
Kovarova M, Benhabbour SR, Massud I. et al.
Citation(s): 
Nat Commun. 2018 Oct 8;9(1):4156. doi: 10.1038/s41467-018-06490-w.
Resource Subcategory: 

 

Non-adherence to medication is an important health care problem, especially in the treatment of chronic conditions. Injectable long-acting (LA) formulations of antiretrovirals (ARVs) represent a viable alternative to improve adherence to HIV/AIDS treatment and prevention. However, the LA-ARV formulations currently in clinical trials cannot be removed after administration even if adverse events occur. Here we show an ultra-LA removable system that delivers drug for up to 9 months and can be safely removed to stop drug delivery. 

Extended-Duration MK-8591-Eluting Implant as a Candidate for HIV Treatment and Prevention

Author(s): 
Barrett S.E., Teller R. S., Forster S. P, et al.
Citation(s): 
Antimicrob Agents Chemother. 2018 Sep 24;62(10). pii: e01058-18. doi: 10.1128/AAC.01058-18. Print 2018 Oct.
Resource Subcategory: 

Regimen adherence remains a major hurdle to the success of daily oral drug regimens for the treatment and prevention of human immunodeficiency virus (HIV) infection. Long-acting drug formulations requiring less-frequent dosing offer an opportunity to improve adherence and allow for more forgiving options with regard to missed doses. The administration of long-acting formulations in a clinical setting enables health care providers to directly track adherence.

Modelling the long-acting administration of anti-tuberculosis agents using PBPK: a proof of concept study

Author(s): 
Rajoli, R. K. R. Podany, A. T. Moss, D. M. et al.
Citation(s): 
Int J Tuberc Lung Dis 22(8):937–944


SETTING: Anti-tuberculosis formulations necessitate uninterrupted treatment to cure tuberculosis (TB), but are characterised by suboptimal adherence, which jeopardises therapeutic efficacy. Long-acting injectable (LAI) formulations or implants could address these associated issues.

OBJECTIVE: niazid, rifapentine, bedaquiline and delamanid—in adults for treatment for latent tuberculous infection (LTBI).

Long-acting injectables for tuberculosis prophylaxis and treatment: is now the time?

Author(s): 
Dooley, K E.
Citation(s): 
Int J Tuberc Lung Dis 22(8):833–834


TUBERCULOSIS (TB) is a wily and enduring foe, responsible for 1 billion deaths in the last 200 years. With the introduction of antibiotics active against Mycobacterium tuberculosis in the 1950s, TB disease could finally be cured with multidrug therapy. TB drugs must still be given for months, generally via directly observed therapy, which is intrusive, expensive, and inconvenient.

Recent developments of nanotherapeutics for targeted and long-acting, combination HIV chemotherapy

Author(s): 
Kraft JC, Treuting PM, Ho RJY
Citation(s): 
J Drug Target. 2018 Jun - Jul;26(5-6):494-504. doi: 10.1080/1061186X.2018.1433681. Epub 2018 Feb 12.


​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.

Mechanism-based pharmacokinetic (MBPK) models describe the complex plasma kinetics of three antiretrovirals delivered by a long-acting anti-HIV drug combination nanoparticle formulation.

Author(s): 
Kraft JC, Treuting PM, Ho RJY
Citation(s): 
J Drug Target. 2018 Jun - Jul;26(5-6):494-504. doi: 10.1080/1061186X.2018.1433681. Epub 2018 Feb 12.


​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.

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

Author(s): 
Kraft JC, Treuting PM, Ho RJY
Citation(s): 
J Drug Target. 2018 Jun - Jul;26(5-6):494-504. doi: 10.1080/1061186X.2018.1433681. Epub 2018 Feb 12.

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. However, indocyanine green (ICG), a common clinical NIR fluorophore, is unstable in aqueous environments and under light exposure, and its poor lymphatic distribution and retention limits its use as a NIR lymphatic tracer. 

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

Author(s): 
Kraft JC, Treuting PM, Ho RJY
Citation(s): 
J Drug Target. 2018 Jun - Jul;26(5-6):494-504. doi: 10.1080/1061186X.2018.1433681. Epub 2018 Feb 12.


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. 

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

Author(s): 
McConnachie LA, Kinman LM, Koehn J, et al.
Citation(s): 
J Pharm Sci. 2018 Jul;107(7):1787-1790. doi: 10.1016/j.xphs.2018.03.005. Epub 2018 Mar 13.


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. 

Long-acting injectable atovaquone nanomedicines for malaria prophylaxis

Author(s): 
Bakshi RP, Tatham LM, Savage AC, et al.
Citation(s): 
Nature Communications 9, Article number: 315 (2018)


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

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