Microsuspension of fatty acid esters of entecavir for parenteral sustained delivery

Ho, Myoung Jin; Lee, Dae Ro; Im, Sung Hyun; Yoon, Ji‐Young; Shin, Chang Yong; Kim, Hyun Jung; Jang, Sun Woo; Choi, Young Wook; Han, Young Taek; Kang, Myung Joo

doi:10.1016/j.ijpharm.2018.03.042

Cited by 21 publications

(20 citation statements)

References 19 publications

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“…However, the oral administration of E is associated with poor patient compliance and adverse reactions, resulting from intake of E on empty stomach, necessitating the fabrication of sustained release formulation [6]. In this context, long-acting parenteral formulations of E have been well-investigated by various research groups, including liquid crystals [12], lipidic prodrug [13], albumin nanoparticles [8] and PLGA microspheres [6].…”

Section: Introductionmentioning

confidence: 99%

An integrated vitamin E-coated polymer hybrid nanoplatform: A lucrative option for an enhanced in vitro macrophage retention for an anti-hepatitis B therapeutic prospect

et al. 2020

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A platform capable of specifically delivering an antiviral drug to the liver infected with hepatitis B is a major concern in hepatology. Vaccination has had a major effect on decreasing the emerging numbers of new cases of infection. However, the total elimination of the hepatitis B virus from the body requires prolonged therapy. In this work, we aimed to target the liver macrophages with lipid polymer hybrid nanoparticles (LPH), combining the merit of polymeric nanoparticles and lipid vesicles. The hydrophilic antiviral drug, entecavir (E), loaded LPH nanoparticles were optimized and physicochemically characterized. A modulated lipidic corona, as well as, an additional coat with vitamin E were used to extend the drug release enhance the macrophage uptake. The selected vitamin E coated LPH nanoparticles enriched with lecithin-glyceryl monostearate lipid shell exhibited high entrapment for E (80.47%), a size � 200 nm for liver passive targeting, extended release over one week, proven serum stability, retained stability after refrigeration storage for 6 months. Upon macrophage uptake in vitro assessment, the presented formulation displayed promising traits, enhancing the cellular retention in J774 macrophages cells. In vivo and antiviral activity futuristic studies would help in the potential application of the ELPH in hepatitis B control.

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Section: Introductionmentioning

confidence: 99%

An integrated vitamin E-coated polymer hybrid nanoplatform: A lucrative option for an enhanced in vitro macrophage retention for an anti-hepatitis B therapeutic prospect

et al. 2020

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“…S7 and S8 in ESI†). The slow and sustained release over several days that we observed with our conjugates is in contrast to entecavir (an antiretroviral used to treat hepatitis B virus (HBV) infection) fatty acid conjugate achieved through similar chemistry where a significant amount of active antiretroviral (15–41%) was released within the first hour (Ho et al, 2018).…”

Section: Resultsmentioning

confidence: 87%

Injectable long-acting human immunodeficiency virus antiretroviral prodrugs with improved pharmacokinetic profiles

Krovi

Gallovic

Keller

et al. 2018

International Journal of Pharmaceutics

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While highly active antiretroviral therapy (HAART) has significantly reduced mortality rates in patients with human immunodeficiency virus type 1 (HIV-1), its efficacy may be impeded by emergence of drug resistance caused by lack of patient adherence. A therapeutic strategy that requires infrequent drug administration as a result of sustained release of antiretroviral drugs would put less burden on the patient. Long-acting antiretroviral prodrugs for HIV therapy were synthesized through modification of the active drugs, emtricitabine (FTC) and elvitegravir (EVG), with docosahexaenoic acid (DHA) in one-step, one-pot, high-yielding reactions. The in vitro drug release profiles of these synthetic conjugates demonstrated sustained and controlled release of the active drug over a period of 3–4weeks attributable to the hydrolysis of the chemical linker in conjunction with the hydrophilicity of the parent drug. Both conjugates exhibited superior antiviral activities in tissue culture models of HIV replication as compared to those of the free drugs, strengthening their role as potent prodrugs for HIV therapy. Pharmacokinetic analysis in CD1 mice further confirmed the long-acting aspect of these conjugates with released drug concentrations in plasma detected at their respective IC90/IC95 values over a period of 2 weeks and discernable amounts of active drug even at 6weeks. Our findings suggest that the injectable small molecule conjugates could be used as long-acting controlled release of FTC and EVG in attempts to mitigate adherence-related HIV resistance.

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“…135 After subcutaneous injection of entecavir in beagle dogs, the C max (4.70 ng/ mL) was protracted, and the t 1/2 value was lengthened (129.30 h) compared to oral administration (15.40ng/mL, 4.1 h). 136 After intravenous administration of acyclovir solution, there was 90-fold higher C max (~26.23 μg/mL) and considerably shorter T max (~8.00 min) compared to that of acyclovir suspension by oral administration (C max was ~0.29 μg/mL and T max was ~26.00 min). 137 After intravenous administration of oseltamivir solution 92…”

Section: Effect Of Administration Route On Pharmacokinetics Of Avdsmentioning

confidence: 95%

“…After subcutaneous injection of the entecavir prodrug in beagle dogs, the plasma drug concentration was markedly protracted (T 1/2 is 129.3 h) with a lower maximum plasma concentration (C max is 4.7 ng/mL) compared to entecavir (oral administration, T 1/2 is 4.09 h and C max is 15.4 ng/ mL). 136 The chloroquine prodrug hydroxychloroquine had higher accumulation in cells and a longer elimination halflife, resulting in a more effect against SARS-CoV-2 infection. 151…”

Section: Effect Of Prodrugs On Pharmacokinetics Of Avdsmentioning

confidence: 99%

Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics

Chen¹,

Wang²,

Song³

et al. 2021

IJN

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Antiviral drugs (AvDs) are the primary resource in the global battle against viruses, including the recent fight against corona virus disease 2019 . Most AvDs require multiple medications, and their use frequently leads to drug resistance, since they have poor oral bioavailability and low efficacy due to their low solubility/low permeability. Characterizing the in vivo metabolism and pharmacokinetic characteristics of AvDs may help to solve the problems associated with AvDs and enhance their efficacy. In this review of AvDs, we systematically investigated their structure-based metabolic reactions and related enzymes, their cellular pharmacology, and the effects of metabolism on AvD pharmacodynamics and pharmacokinetics. We further assessed how delivery systems achieve better metabolism and pharmacology of AvDs. This review suggests that suitable nanosystems may help to achieve better pharmacological activity and pharmacokinetic behavior of AvDs by altering drug metabolism through the utilization of advanced nanotechnology and appropriate administration routes. Notably, such AvDs as ribavirin, remdesivir, favipiravir, chloroquine, lopinavir and ritonavir have been confirmed to bind to the severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) receptor and thus may represent anti-COVID-19 treatments. Elucidating the metabolic and pharmacokinetic characteristics of AvDs may help pharmacologists to identify new formulations with high bioavailability and efficacy and help physicians to better treat virus-related diseases, including COVID-19.

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Microsuspension of fatty acid esters of entecavir for parenteral sustained delivery

Cited by 21 publications

References 19 publications

An integrated vitamin E-coated polymer hybrid nanoplatform: A lucrative option for an enhanced in vitro macrophage retention for an anti-hepatitis B therapeutic prospect

An integrated vitamin E-coated polymer hybrid nanoplatform: A lucrative option for an enhanced in vitro macrophage retention for an anti-hepatitis B therapeutic prospect

Injectable long-acting human immunodeficiency virus antiretroviral prodrugs with improved pharmacokinetic profiles

Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics

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