Formulation, In Vitro and In Vivo Pharmacokinetics of Anti-HIV Vaginal Bioadhesive Gel

The aim of this study was to explore the anti-diabetic effects of mogroside V (MV) and its aglycone mogrol (MO), both isolated from the fruits of Siraitia grosvenorii Swingle, and to investigate the pharmacokinetic behaviors of MV and its metabolite MO in rats.

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In Vitro and In Silico Antioxidant, Anti-Diabetic, Anti-HIV and Anti-Alzheimer Activity of Endophytic Fungi, Cladosporium uredinicola Phytochemicals

International Journal of Pharmacology Phytochemistry and Ethnomedicine ◽

10.18052/www.scipress.com/ijppe.13.13 ◽

2019 ◽

Vol 13 ◽

pp. 13-34

Author(s):

Melappa Govindappa ◽

V. Thanuja ◽

S. Tejashree ◽

C.A. Soukhya ◽

Suresh Barge ◽

...

Keyword(s):

Qualitative Method ◽

Cholinesterase Activity ◽

Methanol Extract ◽

High Binding Energy ◽

Acetyl Cholinesterase ◽

Gp 120 ◽

Anti Hiv ◽

Hiv 1

The present work was aimed to identify phytochemicals in C. uredinicola methanol extract from qualitative, TLC and GC-MS method and evaluated for antioxidant, anti-HIV, anti-diabetes, anti-cholinesterase activity in vitro and in silico. The C. uredinicola extract showed flavonoids, tannins, alkaloids, glycosides, phenols, terpenoids, and coumarins presence in qualitative method. From GC-MS analysis, identified seven different phytochemicals and out of seven, four (coumarin, coumarilic acid, hymecromone, alloisoimperatorin) are coumarins. The C. uredinicola extract have shown significant antioxidant activity in DPPH (73) and FRAP (1359) method. The HIV-1 RT (83.81+2.14), gp 120 (80.24+2.31), integrase (79.43+3.14) and protease (77.63+2.14), DPPIV, β-glucosidase and acetyl cholinesterase activity was significantly reduced by the extract. The 2-diphenylmethyleneamino methyl ester had shown significant interaction with oxidant and HIV-1 proteins whereas alloisoimperatorin have interacted with diabetes and cholinesterase proteins followed by hymecromone with high binding energy. These three phytochemicals are non-carcinogens, non-toxic, readily degradable and have drug likeliness properties. The C. uredinicola phytochemicals are responsible for management of diabetes, HIV-1 and Alzheimer. Further in vivo work is needed to justify our research.

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In VitroDrug Combination Studies of Letermovir (AIC246, MK-8228) with Approved Anti-Human Cytomegalovirus (HCMV) and Anti-HIV Compounds in Inhibition of HCMV and HIV Replication

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00114-15 ◽

2015 ◽

Vol 59 (6) ◽

pp. 3140-3148 ◽

Cited By ~ 20

Author(s):

Steffen Wildum ◽

Holger Zimmermann ◽

Peter Lischka

Keyword(s):

Human Cytomegalovirus ◽

Treatment Strategies ◽

Opportunistic Pathogen ◽

Multidrug Resistant ◽

Severe Toxicity ◽

Transplant Recipients ◽

Hiv Drugs ◽

Anti Hiv

ABSTRACTDespite modern prevention and treatment strategies, human cytomegalovirus (HCMV) remains a common opportunistic pathogen associated with serious morbidity and mortality in immunocompromised individuals, such as transplant recipients and AIDS patients. All drugs currently licensed for the treatment of HCMV infection target the viral DNA polymerase and are associated with severe toxicity issues and the emergence of drug resistance. Letermovir (AIC246, MK-8228) is a new anti-HCMV agent in clinical development that acts via a novel mode of action and has demonstrated anti-HCMV activityin vitroandin vivo. For the future, drug combination therapies, including letermovir, might be indicated under special medical conditions, such as the emergence of multidrug-resistant virus strains in transplant recipients or in HCMV-HIV-coinfected patients. Accordingly, knowledge of the compatibility of letermovir with other HCMV or HIV antivirals is of medical importance. Here, we evaluated the inhibition of HCMV replication by letermovir in combination with all currently approved HCMV antivirals using cell culture checkerboard assays. In addition, the effects of letermovir on the antiviral activities of selected HIV drugs, and vice versa, were analyzed. Using two different mathematical techniques to analyze the experimental data, (i) additive effects were observed for the combination of letermovir with anti-HCMV drugs and (ii) no interaction was found between letermovir and anti-HIV drugs. Since none of the tested drug combinations significantly antagonized letermovir efficacy (or vice versa), our findings suggest that letermovir may offer the potential for combination therapy with the tested HCMV and HIV drugs.

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Resistance mutations selected in vivo under therapy with anti-HIV drug HBY 097 differ from resistance pattern selected in vitro

Antiviral Research ◽

10.1016/s0166-3542(99)00010-8 ◽

1999 ◽

Vol 42 (1) ◽

pp. 15-24 ◽

Cited By ~ 14

Author(s):

H RUBSAMENWAIGMANN ◽

E HUGUENEL ◽

A SHAH ◽

A PAESSENS ◽

H RUOFF ◽

...

Keyword(s):

Resistance Pattern ◽

Resistance Mutations ◽

Anti Hiv

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Lactoferrin nanoparticles coencapsulated with curcumin and tenofovir improve vaginal defense against HIV-1 infection

Nanomedicine ◽

10.2217/nnm-2020-0347 ◽

2021 ◽

Author(s):

Samrajya Lakshmi Yeruva ◽

Prashant Kumar ◽

Seetharam Deepa ◽

Anand K Kondapi

Keyword(s):

Physicochemical Characterization ◽

Systemic Circulation ◽

Application Site ◽

Drug Nanoparticles ◽

In Vivo Experiments ◽

Hiv Microbicide ◽

Anti Hiv ◽

Hiv 1

Aim: We report here the development of tenofovir- and curcumin-loaded lactoferrin nanoparticles (TCNPs) as an HIV-microbicide. Materials & methods: TCNPs were subjected to various physicochemical characterization experiments, followed by in vitro and in vivo experiments to assess their efficacy. Results: TCNPs had a diameter of 74.31 ± 2.56 nm with a gross encapsulation of more than 61% for each drug. Nanoparticles were effective against HIV-1 replication, with an IC50 of 1.75 μM for curcumin and 2.8 μM for tenofovir. TCNPs provided drug release at the application site for up to 8–12 h, with minimal leakage into the systemic circulation. TCNPs showed spermicidal activity at ≥200 μM and induced minimal cytotoxicity and inflammation in the vaginal epithelium as revealed by histopathological and ELISA studies. Conclusion: We demonstrated that TCNPs could serve as a novel anti-HIV microbicidal agent in rats. [Formula: see text]

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Cefmetazole as an Alternative to Carbapenems Against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Infections Based on In Vitro and In Vivo Pharmacokinetics/Pharmacodynamics Experiments

Pharmaceutical Research ◽

10.1007/s11095-021-03140-7 ◽

2021 ◽

Author(s):

Wataru Takemura ◽

Sho Tashiro ◽

Marina Hayashi ◽

Yuki Igarashi ◽

Xiaoxi Liu ◽

...

Keyword(s):

Escherichia Coli ◽

Beta Lactamase ◽

Extended Spectrum Beta Lactamase ◽

Extended Spectrum ◽

In Vivo Pharmacokinetics

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Emergence of Nanotechnology to Fight HIV Sexual Transmission: The Trip of G2-S16 Polyanionic Carbosilane Dendrimer to Possible Pre-Clinical Trials

International Journal of Molecular Sciences ◽

10.3390/ijms21249403 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9403

Author(s):

Ignacio Relaño-Rodríguez ◽

Maria Ángeles Muñoz-Fernández

Keyword(s):

Clinical Trials ◽

Histopathological Examination ◽

Early Stage ◽

Sexual Transmission ◽

Reaction Times ◽

Vaginal Mucosa ◽

Carbosilane Dendrimer ◽

Anti Hiv

Development of new, safe, and effective microbicides to prevent human immunodeficiency virus HIV sexual transmission is needed. Unfortunately, most microbicides proved ineffective to prevent the risk of HIV-infection in clinical trials. We are working with G2-S16 polyanionic carbosilane dendrimer (PCD) as a new possible vaginal topical microbicide, based on its short reaction times, wide availability, high reproducibility, and quantitative yields of reaction. G2-S16 PCD exerts anti-HIV activity at an early stage of viral replication, by blocking gp120/CD4/CCR5 interaction, and providing a barrier against infection for long periods of time. G2-S16 PCD was stable at different pH values, as well as in the presence of seminal fluids. It maintained the anti-HIV activity against R5/X4 HIV over time, did not generate any type of drug resistance, and retained the anti-HIV effect when exposed to semen-enhanced viral infection. Importantly, G2-S16 PCD did not modify vaginal microbiota neither in vitro or in vivo. Histopathological examination did not show vaginal irritation, inflammation, lesions, or damage in the vaginal mucosa, after administration of G2-S16 PCD at different concentrations and times in female mice and rabbit animal models. Based on these promising data, G2-S16 PCD could become a good, safe, and readily available candidate to use as a topical vaginal microbicide against HIV.

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