Transformation of dolutegravir into an ultra-long-acting parenteral prodrug formulation

Deodhar, Suyash; Sillman, Brady; Bade, Aditya N.; Avedissian, Sean N.; Podany, Anthony T.; McMillan, JoEllyn M; Gautam, Nagsen; Hanson, Brandon; Shetty, Bhagya Laxmi Dyavar; Szlachetka, Adam M.; Johnston, Morgan; Thurman, Michellie; Munt, Daniel J; Dash, Alekha K.; Marković, Milica; Dahan, Arik; Alnouti, Yazen; Yazdi, Alborz; Kevadiya, Bhavesh D.; Byrareddy, Siddappa N.; Cohen, Samuel M.; Edagwa, Benson; Gendelman, Howard E.

doi:10.1038/s41467-022-30902-7

“…As widely reported for other disease areas, nanomedicine can overcome the limitations of the current PF therapies [52], [53]. Nanotherapies like nanoparticles, cellderived vesicles, nanopolymers are more amenable to modification to enhance their safety, specificity, and stimuli-responsive drug release [54], [55]. Additionally, there have been multiple reports of tailoring pharmacokinetics of drugs by using nanomedicinebased approaches [56].…”

Section: Current Status Of Covid-induced Pf Therapymentioning

confidence: 99%

Nano-Therapeutic Approaches to Treat COVID Induced Pulmonary Fibrosis

Kanvinde¹,

Deodhar²,

Kulkarni³

et al. 2023

Preprint

0

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There have been significant collaborative efforts over the past three years to develop therapies against COVID-19. During this journey, there has also been a lot of focus on understanding at-risk groups of patients who either have pre-existing conditions or have developed concomitant health conditions due to the impact of COVID-19 on immune system. There was a high incidence of COVID-19 induced pulmonary fibrosis (PF) observed in patients. PF can cause significant morbidity, long-term disability, and lead to death in the long run. Additionally, being a progressive disease, PF can also impact the patient for a long time after COVID infection and affect the overall quality of life. Although current therapies are being used as the mainstay for treating PF, there is no therapy specifically for COVID-induced PF. As observed in the treatment of other diseases, nanomedicine can show a significant promise in overcoming the limitations of current anti-PF therapies. In this review, we summarize the efforts reported by various groups to develop nanomedicine therapeutics to treat COVID-induced PF.

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“…As widely reported for other disease areas, nanomedicine can overcome the limitations of the current PF therapies [ 52 , 53 ]. Nanotherapies such as nanoparticles, cell-derived vesicles, and nanopolymers are more amenable to modification to enhance their safety, specificity, and stimuli-responsive drug release [ 54 , 55 ]. Additionally, there have been multiple reports of tailoring the pharmacokinetics of drugs by using nanomedicine-based approaches [ 56 ].…”

Section: Current Status Of Covid-19-induced Pf Therapymentioning

confidence: 99%

Nanotherapeutic Approaches to Treat COVID-19-Induced Pulmonary Fibrosis

Kanvinde

¹

,

Deodhar

²

,

Kulkarni

³

et al. 2023

BioTech

Self Cite

0

View full text Add to dashboard Cite

There have been significant collaborative efforts over the past three years to develop therapies against COVID-19. During this journey, there has also been a lot of focus on understanding at-risk groups of patients who either have pre-existing conditions or have developed concomitant health conditions due to the impact of COVID-19 on the immune system. There was a high incidence of COVID-19-induced pulmonary fibrosis (PF) observed in patients. PF can cause significant morbidity and long-term disability and lead to death in the long run. Additionally, being a progressive disease, PF can also impact the patient for a long time after COVID infection and affect the overall quality of life. Although current therapies are being used as the mainstay for treating PF, there is no therapy specifically for COVID-induced PF. As observed in the treatment of other diseases, nanomedicine can show significant promise in overcoming the limitations of current anti-PF therapies. In this review, we summarize the efforts reported by various groups to develop nanomedicine therapeutics to treat COVID-induced PF. These therapies can potentially offer benefits in terms of targeted drug delivery to lungs, reduced toxicity, and ease of administration. Some of the nanotherapeutic approaches may provide benefits in terms of reduced immunogenicity owing to the tailored biological composition of the carrier as per the patient needs. In this review, we discuss cellular membrane-based nanodecoys, extracellular vesicles such as exosomes, and other nanoparticle-based approaches for potential treatment of COVID-induced PF.

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“…The nanosuspension of VM1500A (deselsulfavirine; NNRTI), a parent drug of elsulfavirine [ 116 ], has been tested in a Phase 1 study, which demonstrated that a monthly injection was well tolerated and had an acceptable PK profile [ 117 ]. Gendelman et al developed CAB [ 70 ] and DTG [ 71 ] fatty acid prodrug-based LA injectable poloxamer nanocrystals [ 72 , 73 , 118 ]. CAB nanoformulations were tested in different animals and showed CAB plasma levels above the PA-IC 90 (~167 ng/ml) for up to a year [ 119 , 120 ].…”

Section: Approaches To Improving Existing Arvs For La Hiv Preventionmentioning

confidence: 99%

Long-acting HIV pre-exposure prophylaxis (PrEP) approaches: recent advances, emerging technologies, and development challenges

Agrahari

¹

,

Anderson

²

,

Peet

³

et al. 2022

Expert Opinion on Drug Delivery

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Introduction: Poor or inconsistent adherence to daily oral pre-exposure prophylaxis (PrEP) has emerged as a key barrier to effective HIV prevention. The advent of potent long-acting (LA) antiretrovirals (ARVs) in conjunction with advances in controlled release technologies has enabled LA ARV drug delivery systems (DDS) capable of providing extended dosing intervals and overcome the challenge of suboptimal drug adherence with daily oral dosing. Areas covered: This review discusses the current state of the LA PrEP field, recent advances, and emerging technologies, including ARV prodrug modifications and new DDS. Technological challenges, knowledge gaps, preclinical testing considerations, and future directions important in the context of clinical translation and implementation of LA HIV PrEP are discussed. Expert opinion: The HIV prevention field is evolving faster than ever and the bar for developing next-generation LA HIV prevention options continues to rise. The requirements for viable LA PrEP products to be implemented in resource-limited settings are challenging, necessitating proactive consideration and product modifications during the design and testing of promising new candidates. If successfully translated, next-generation LA PrEP that are safe, affordable, highly effective, and accepted by both end-users and key stakeholders will offer significant potential to curb the HIV pandemic.

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Transformation of dolutegravir into an ultra-long-acting parenteral prodrug formulation

Cited by 33 publications

References 47 publications

Nano-Therapeutic Approaches to Treat COVID Induced Pulmonary Fibrosis

Nano-Therapeutic Approaches to Treat COVID Induced Pulmonary Fibrosis

Nanotherapeutic Approaches to Treat COVID-19-Induced Pulmonary Fibrosis

Long-acting HIV pre-exposure prophylaxis (PrEP) approaches: recent advances, emerging technologies, and development challenges

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