Article
Chemistry, Multidisciplinary
Duy-Khiet Ho, Clare LeGuyader, Selvi Srinivasan, Debashish Roy, Vladimir Vlaskin, Thomas E. J. Chavas, Ciana L. Lopez, Jessica M. Snyder, Almar Postma, John Chiefari, Patrick S. Stayton
Summary: A new injectable depot platform has been developed with a new mechanism for controlled drug release, aimed at improving patient adherence and releasing tenofovir alafe-namide (TAF) effectively. This platform has the potential for long-acting treatment benefits and sustained drug release profiles over a period of time.
JOURNAL OF CONTROLLED RELEASE
(2021)
Editorial Material
Microbiology
Amit Sharma
Summary: Two recent publications highlight highly potent inhibitors as potential candidates for HIV pre-exposure prophylaxis (PrEP). They provide solid evidence that long-acting capsid or fusion inhibitors administered as PrEP can offer robust protection against simian-human immunodeficiency virus in the rhesus macaque model of HIV infection.
CELL HOST & MICROBE
(2022)
Article
Public, Environmental & Occupational Health
Beatriz Grinsztejn, Thiago Silva Torres, Brenda Hoagland, Emilia Moreira Jalil, Ronaldo Ismerio Moreira, Gabrielle O'Malley, Starley B. Shade, Marcos R. Benedetti, Julio Moreira, Keila Simpson, Maria Cristina Pimenta, Valdilea Goncalves Veloso, ImPrEP CAB Brasil Study Team
Summary: ImPrEP CAB Brasil is an implementation study in Brazil aiming to evaluate the effectiveness of long-acting injectable cabotegravir (CAB-LA) for preexposure prophylaxis (PrEP) and identify effective implementation approaches, especially among young sexual and gender minorities (SGMs). The study includes formative work, qualitative assessments, and clinical steps 1 to 4. The outcomes of interest include PrEP acceptability, choice, effectiveness, implementation, and feasibility. This study is important for designing programmatic strategies for PrEP programs and reducing HIV incidence among SGMs in Brazil and other countries in the Global South.
JMIR PUBLIC HEALTH AND SURVEILLANCE
(2023)
Review
Infectious Diseases
Joerg J. Moehrle
Summary: Traditional malaria drug discovery has focused on orally available drugs. However, there is now interest in injectable medicines, such as monoclonal antibodies (mAbs) with long-lasting plasma half-lives or long-lasting depot formulations of small molecules. These drugs could act as prophylactics targeting earlier parasitic stages or as interventions against infectious gametocytes. Compared to small-molecule drugs, the development of mAbs is less risky and they have a good safety profile. This could provide faster access to new malaria treatments for vulnerable populations.
TROPICAL MEDICINE AND INFECTIOUS DISEASE
(2022)
Review
Pharmacology & Pharmacy
Spencer H. Durham, Ashlee Milam, Dylan Waer, Elias B. Chahine
Summary: This objective review evaluates the pharmacology, pharmacokinetics, efficacy, safety, and role of long-acting injectable cabotegravir (CAB-LA) in HIV preexposure prophylaxis (PrEP). The findings suggest that CAB-LA is more effective than daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in preventing HIV-1 infection among high-risk individuals. The most common adverse effects are injection site reactions (ISRs), which tend to decrease over time. CAB-LA may be particularly useful for individuals with adherence problems, renal impairment, and decreased bone mineral density.
ANNALS OF PHARMACOTHERAPY
(2023)
Review
Public, Environmental & Occupational Health
Wenjing Wang, Shengnan Zhao, Yaxin Wu, Wenshan Duan, Sibo Li, Zhen Li, Caiping Guo, Wen Wang, Tong Zhang, Hao Wu, Xiaojie Huang
Summary: This study investigated the safety and efficacy of long-acting cabotegravir (CAB-LA) and long-acting rilpivirine (RPV-LA) in the prevention and treatment of HIV-1 infection. The results showed that these long-acting antiretrovirals have favorable safety profiles and tolerability, with CAB-LA being more effective in preventing HIV-1 infection compared to current drugs. CAB-LA+RPV-LA can maintain virological suppression for a long time. People living with HIV have a positive attitude towards long-acting antiretrovirals.
JMIR PUBLIC HEALTH AND SURVEILLANCE
(2023)
Article
Chemistry, Multidisciplinary
Go-Wun Choi, Sangno Lee, Dong Wook Kang, Ju Hee Kim, Hea-Young Cho
Summary: Novel formulations of DNP-loaded microspheres with a one-month duration of effect were developed to reduce dosing frequency and improve patient adherence. Various factors affecting drug release were studied, and animal models were used to optimize formulations and evaluate pharmacokinetic properties. The developed PK model was extrapolated to humans to show that a formulation with PLGA 7525A and a DPR of 1/9 could maintain drug concentration for a month with controlled initial burst release.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Pharmacology & Pharmacy
Quanying Bao, Xiaoyi Wang, Yuan Zou, Yan Wang, Diane J. Burgess
Summary: Long-acting injectable suspensions are complex formulations that require controlled drug release. Understanding their in vitro and in vivo performance, as well as the in vitro-in vivo correlation, is crucial to prevent unpredictable drug release and potential side effects. Current recommended in vitro release testing methods have limited release durations, hindering the establishment of in vitro-in vivo correlations for long-acting injectables. Developing testing methods with longer release durations is essential for better correlation between in vitro and in vivo release.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Immunology
Kevin M. Maloney, Adrien Le Guillou, Robert A. Driggers, Supriya Sarkar, Emeli J. Anderson, Amyn A. Malik, Samuel M. Jenness
Summary: The study found that if 50% of people chose LAI-PrEP, 4.3% of infections could be averted over 10 years. LAI-PrEP is expected to have a slightly greater impact than the DO-PrEP-only regimen, especially with assumptions of higher adherence and partial protection after discontinuation. If the total PrEP initiation rate doubled, 17.1% of infections would be averted, pointing to the potential for increased population-level impact with higher PrEP coverage.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Infectious Diseases
Enos Moyo, Grant Murewanhema, Godfrey Musuka, Tafadzwa Dzinamarira
Summary: Sub-Saharan Africa bears the highest burden of HIV-1 and AIDS, with 39% of all new infections globally in 2020 occurring in this region. Oral PrEP has proven to be effective in reducing HIV-1 transmission risk, but its success relies on user adherence. The availability of long-acting injectable PrEP may improve uptake and adherence in individuals who struggle to adhere to oral PrEP. However, implementing long-acting cabotegravir (CAB-LA) as a PrEP option in Africa faces challenges such as cost, refrigeration requirements, and a shortage of healthcare providers trained in administering injectable medicines. Client challenges include lack of knowledge, drug accessibility, side effects, stigma, and lack of family and community support. Lessons from successful implementation of antiretroviral therapy, oral PrEP, and immunization in Africa can guide measures to address these challenges, including advocating for patent licence waivers, conducting demonstration projects, promoting renewable energy sources, healthcare provider training, task shifting, community engagement, client education, and implementing adherence promotion strategies.
TROPICAL MEDICINE AND INFECTIOUS DISEASE
(2022)
Article
Psychiatry
Petru Ifteni, Paula-Simina Petric, Andreea Teodorescu
Summary: This study introduced an index, ROLIN, for evaluating the opportunity for long-acting injectable antipsychotic initiation in patients with schizophrenia. The research found that 56% of patients had a strong indication for LAI treatment initiation. By examining the normal distribution of values, the study concluded that improving treatment for schizophrenia is crucial.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Pharmacology & Pharmacy
Quanying Bao, Xiaoyi Wang, Bo Wan, Yuan Zou, Yan Wang, Diane J. Burgess
Summary: Long-acting injectable aqueous suspensions achieve extended drug release through slow dissolution of drug crystals. Currently, there are around ten FDA-approved LAI aqueous suspensions, and establishing in vitro-in vivo correlation (IVIVC) for these products is challenging. This study successfully established a Level A IVIVC for LAI aqueous suspensions using in vitro release profiles obtained with USP apparatus 4, which is the first report of an IVIVC for this type of suspension.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Multidisciplinary Sciences
Steven A. John, Juan P. Zapata, Madeline Dang, Benedikt Pleuhs, Andrew O'Neil, Sabina Hirshfield, Jennifer L. Walsh, Andrew E. Petroll, Katherine G. Quinn
Summary: In 2021, intramuscular cabotegravir for long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP) was approved by the U.S. FDA. A study was conducted to explore LAI-PrEP decision-making among young sexual minority men (YSMM) aged 17-24. The findings revealed that YSMM had varying preferences and considerations regarding LAI-PrEP, including concerns about adherence, awareness of safety and efficacy data, comfort with injections, minimizing stigma, and the option of self-administration. YSMM recognized the benefits of having more PrEP options for supporting uptake and persistence.
SCIENTIFIC REPORTS
(2023)
Review
Pharmacology & Pharmacy
Reena Sharma, Sheetal Yadav, Vivek Yadav, Junia Akhtar, Oly Katari, Kaushik Kuche, Sanyog Jain
Summary: Long-acting injectable (LAIs) delivery systems sustain drug therapeutic action, reduce dosage and toxicity, and improve patient compliance. Lipid-based depots provide extended drug release and stability, making them suitable for treating chronic ailments. This review summarizes recent advancements in lipid-based LAIs and their potential in managing chronic diseases, as well as the challenges involved in developing them.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Article
Multidisciplinary Sciences
Samuel J. Vidal, Elena Bekerman, Derek Hansen, Bing Lu, Kelly Wang, Judy Mwangi, William Rowe, Federico Campigotto, Jim Zheng, Darryl Kato, Abishek Chandrashekar, Julia Barrett, Shivani Patel, Huahua Wan, Tochi Anioke, Noe B. Mercado, Joseph P. Nkolola, Melissa J. Ferguson, William J. Rinaldi, Christian Callebaut, Wade Blair, Tomas Cihlar, Romas Geleziunas, Stephen R. Yant, Dan H. Barouch
Summary: The study shows that a single subcutaneous injection of GS-CA1 can provide long-term protection against repeated rectal simian-human immunodeficiency virus (SHIV) challenges in rhesus macaques. Pharmacokinetic analysis indicates a correlation between GS-CA1 plasma concentration and protection from SHIV challenges. These proof-of-concept data support the development of capsid inhibitors as a novel long-acting PrEP strategy in humans.
Letter
Pharmacology & Pharmacy
Steven P. Rannard, Tom O. McDonald, Andrew Owen
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Immunology
Ethel D. Weld, Jacqueline Astemborski, Gregory D. Kirk, Mark S. Sulkowski, Stephanie Katz, Richard Rothman, Sunil S. Solomon, Gail Matthews, Yu-Hsiang Hsieh, Malvika Verma, Giovanni Traverso, Susan Swindells, Andrew Owen, Jordan Feld, Charles Flexner, Shruti H. Mehta, David L. Thomas
Summary: A survey on long-acting hepatitis C virus (HCV) treatment preferences, conducted among people with or at risk of HCV, revealed high acceptability of long-acting treatments, which are sometimes preferred to pills; such strategies may accelerate efforts at HCV elimination.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Genetics & Heredity
Rohan Gurjar, Laura Dickinson, Daniel Carr, Wolfgang Stohr, Stefano Bonora, Andrew Owen, Antonio D'Avolio, Adam Cursley, Nathalie De Castro, Gerd Fatkenheuer, Linos Vandekerckhove, Giovanni Di Perri, Anton Pozniak, Christine Schwimmer, Francois Raffi, Marta Boffito
Summary: This study used nonlinear mixed effects modeling to determine the pharmacokinetic parameters of raltegravir and investigate the influence of demographics and SNPs on its pharmacokinetics and pharmacodynamics. The results showed that demographics and SNPs did not significantly affect the pharmacokinetics of raltegravir, and no significant pharmacokinetic/pharmacodynamic relationships were observed. However, at week 96, UGT1A1*28/*28 was associated with lower virological failure.
PHARMACOGENOMICS JOURNAL
(2023)
Article
Immunology
Charles Flexner, Marco Siccardi, Fazila Bunglawala, Andrew Owen
Summary: Developing long-acting drugs and formulations for infectious diseases is considered high risk and low reward by the pharmaceutical industry. The Long-Acting/Extended Release Antiretroviral Research Resource Program (LEAP) was established to accelerate the development of such products and bridge the gaps between different stakeholders. Through a systematic approach and continuous feedback loop, LEAP has contributed to the approval of formulations for HIV and the development of products for tuberculosis and hepatitis B and C. Long-acting drugs have the potential to revolutionize antimicrobial chemotherapy, but face challenges in terms of risk.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Immunology
Megan Neary, Andrew Owen, Adeniyi Olagunju
Summary: The development of more long-acting antiretrovirals and multipurpose technologies in clinical settings in the future will be driven by advancements in novel formulations and delivery systems. The key to successful clinical translation lies in predictive preclinical models that can accurately predict human exposure and response. This article reviews the standard preclinical assessments for long-acting formulations and delivery systems, focusing on the preclinical development of long-acting antiretrovirals for HIV therapy. It summarizes the progress made in the development of novel long-acting antiretroviral formulations and delivery systems, including bispecific broadly neutralizing monoclonal antibodies and small molecule technologies for co-delivery of multiple drugs with different solubility properties. Tissue engineering and 3-dimensional in vitro modeling offer new opportunities for preclinical modeling of anti-infective activity, toxicity assessment, and quantitative modeling and simulation strategies. These developments will likely contribute to the advancement of more long-acting anti-infective drugs and multipurpose technologies into clinical development.
CLINICAL INFECTIOUS DISEASES
(2022)
Letter
Medicine, General & Internal
Andrew Owen, Janet Victoria Diaz, Gordon Guyatt, Francois Lamontagne, Miriam Stegemann, Per Olav Vandvik, Thomas Agoritsas
Article
Chemistry, Applied
Nancy M. Elbaz, Andrew Owen, Steve Rannard, Tom O. McDonald
Summary: This work demonstrates the use of a titration method to produce multilayered coatings on a nanosuspension, enhancing the release behavior and stability of curcumin. The results show that a pH-responsive outer layer delays curcumin release in acidic conditions and facilitates its release in neutral conditions. Increasing the number of layers improves the stability of curcumin in the nanosuspension and reduces its toxicity.
FOOD HYDROCOLLOIDS
(2023)
Article
Virology
Eduardo Gallardo-Toledo, Megan Neary, Joanne Sharp, Joanne Herriott, Edyta Kijak, Chloe Bramwell, Paul Curley, Usman Arshad, Henry Pertinez, Rajith K. R. Rajoli, Anthony Valentijn, Helen Cox, Lee Tatham, Anja Kipar, James P. Stewart, Andrew Owen
Summary: This study investigated the chemoprophylactic and therapeutic efficacy of Pibrentasvir (PIB), Favipiravir (FVP), and Remdesivir (RDV) alone or in combination against SARS-CoV-2. The results showed that RDV alone prevented transmission, while other drugs reduced the viral load after contact transmission. However, no additional benefit was observed when combining FVP or RDV with PIB.
Article
Multidisciplinary Sciences
Victoria A. Balta, Deborah Stiffler, Abeer Sayeed, Abhai K. Tripathi, Rubayet Elahi, Godfree Mlambo, Rahul P. Bakshi, Amanda G. Dziedzic, Anne E. Jedlicka, Elizabeth Nenortas, Keyla Romero-Rodriguez, Matthew A. Canonizado, Alexis Mann, Andrew Owen, David J. Sullivan, Sean T. Prigge, Photini Sinnis, Theresa A. Shapiro
Summary: Atovaquone-resistant parasites show multiple defects in mosquitoes, reducing the likelihood of transmission in the field.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Paul Curley, James J. Hobson, Neill J. Liptrott, Edward Makarov, Amer Al-khouja, Lee Tatham, Christopher A. W. David, Helen Box, Megan Neary, Joanne Sharp, Henry Pertinez, David Meyers, Charles Flexner, Caren L. Freel Meyers, Larisa Poluektova, Steve Rannard, Andrew Owen
Summary: The study reports the feasibility and predicted antiviral activity of the semi-solid prodrug nanoparticle (SSPN) long-acting injectable (LAI) formulation for the prevention of HIV infection. Preclinical assessments show that the formulation has a prolonged pharmacokinetic half-life in animal models and can effectively suppress viral loads to prevent and control HIV infection.
Correction
Immunology
Clifford T. H. Hayashi, Yi Cao, Leor C. C. Clark, Abhai K. K. Tripathi, Fidel Zavala, Garima Dwivedi, James Knox, Mohamad-Gabriel Alameh, Paulo J. C. Lin, Ying K. K. Tam, Drew Weissman, Nirbhay Kumar
Article
Engineering, Biomedical
Edyta Niezabitowska, Dominic M. M. Gray, Eduardo Gallardo-Toledo, Andrew Owen, Steve P. P. Rannard, Tom O. O. McDonald
Summary: Core-shell nanogels consisting of poly(N-isopropylmethacrylamide) core and poly(N-isopropylacrylamide) shell crosslinked with a degradable crosslinker were synthesized. The degradation behavior of these nanogels was characterized using asymmetric flow field flow fractionation coupled with multi-angle and dynamic light scattering. The results revealed slower degradation of the core-shell nanogels compared to their non-core-shell counterparts, possibly due to a higher degree of self-crosslinking reactions in the shell. Majority of the degradation products had molecule weights below 10 kDa, suggesting renal clearance.
JOURNAL OF FUNCTIONAL BIOMATERIALS
(2023)
Article
Medicine, General & Internal
Bozana Obradovic, Owain Roberts, Andrew Owen, Ivana Milosevic, Natasa Milic, Jovan Ranin, Gordana Dragovic
Summary: This study investigates the gene expression of CYP2B6, CYP3A4, and ABCB1 transporters in HIV, HCV, and HIV/HCV co-infected patients, and their potential association with therapy choice and liver damage parameters. The results show that CYP2B6 mRNA levels are significantly increased in co-infected patients, while HIV infection is significantly associated with increased CYP3A4 mRNA levels. A trend towards downregulation of ABCB1 expression is observed in patients using lamivudine.
MEDICINA-LITHUANIA
(2023)
Article
Chemistry, Multidisciplinary
Sam Morris, Mark Long, Alison Savage, Andrew Owen, Steve Rannard, Helen Cauldbeck
Summary: The inherent barrier properties of the skin present significant challenges for the transdermal delivery of drugs. In this study, the ex vivo transdermal permeation and deposition of an anti-malarial prophylactic, atovaquone solid drug nanoformulation, was radiometrically evaluated following the application of a solid microneedle format.
NANOSCALE ADVANCES
(2023)
Article
Materials Science, Biomaterials
Anika Shakil, Faye Y. Hern, Chung Liu, Kartik Temburnikar, Pierre Chambon, Neill Liptrott, Tom O. McDonald, Megan Neary, Andrew Owen, Caren Freel Meyers, Steve P. Rannard
Summary: Long-acting drug delivery is an increasingly important area that tackles challenges related to patient adherence and pill burden in chronic illness. In this study, the highly water soluble nucleoside reverse transcriptase inhibitor FTC was used as a novel A-B monomer in step-growth polymerization with chloroformate functional C-n monomers to create poly(carbamate/carbonate) structures with different architectures. These polymer prodrugs were solid at room temperature and released FTC when exposed to mixed gender human plasma.
JOURNAL OF MATERIALS CHEMISTRY B
(2022)
