The Pre-clinical Toolbox of Pharmacokinetics and Pharmacodynamics: in vitro and ex vivo Models

Herrera, Carolina

doi:10.3389/fphar.2019.00578

Cited by 6 publications

(4 citation statements)

References 183 publications

(224 reference statements)

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“…By contrast, due to the extensive efforts to develop a vaginally applied microbicide for HIV prevention, a comprehensive preclinical toolbox has been developed to assess these vaginal products, and the failure of early clinical trials to clearly demonstrate the effectiveness of these vaginal microbicides have prompted further refinement in preclinical testing. As a result, numerous biomarkers have been developed to assess the microbicidal activity of vaginal microbicides 49,81–85 . A similar situation is found in the assisted reproductive technology field, where biomarkers for predicting fertility are the subject of continuing research, with the goal of improving pregnancy outcomes 86,87 …”

Section: Discussionmentioning

confidence: 87%

Evaluation of the novel vaginal contraceptive agent PPCM in preclinical studies using sperm hyaluronan binding and acrosome status assays

et al. 2021

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Background: Polyphenylene carboxymethylene (PPCM) sodium salt is a promising multipurpose technology for prevention of both sexually transmitted infections (STIs) and pregnancy. In preclinical studies, PPCM has demonstrated significant (1) antimicrobial activity against several important viral and bacterial pathogens and (2) contraceptive activity associated with premature acrosome loss.Objective: To further evaluate a vaginal antimicrobial compound as a contraceptive agent in preclinical studies utilizing a repurposed hyaluronan binding assay (HBA). Materials and methods:Semen samples containing either neat semen or washed spermatozoa were treated with increasing concentrations of PPCM or calcium ionophore A23187 (positive control). Sperm inactivation was measured by two methods: (1) double acrosome staining (AS), and (2) a hyaluronan binding assay (HBA ® ). Percentage of inactivated sperm was compared between untreated control sperm and those treated with PPCM or A23187.Results: PPCM had a significant (p < 0.05) and dose-dependent effect on sperm inactivation in both assays, with HBA detecting a higher proportion of inactivated sperm than AS. PPCM did not affect sperm motility and exhibited equivalent responses in the neat and washed samples.Discussion: Both HBA and AS confirmed that spermatozoa were rapidly inactivated at PPCM concentrations likely present in the vagina under actual use conditions and in a time-frame comparable to in vivo migration of spermatozoa out of seminal plasma into cervical mucus. Conclusion: PPCM vaginal gel may provide contraceptive protection as well as helpwith STI prevention. HBA may be a sensitive and much needed biomarker for sperm activity in future contraceptive development.

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Section: Discussionmentioning

confidence: 87%

Evaluation of the novel vaginal contraceptive agent PPCM in preclinical studies using sperm hyaluronan binding and acrosome status assays

et al. 2021

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“…In drug discovery and drug delivery research there is a constant need for viable and reliable alternatives for in vitro drug efficacy and toxicity testing. Cellbased assays are critical in the pre-clinical drug discovery and development process with the advancements of 3D cell cultures, analytical assays require to be adapted [79]. Method validation is a series of tests intended to guarantee that an analytical method is suitable for its intended purpose and capable of producing useful and authentic analytical results [80].…”

Section: Discussionmentioning

confidence: 99%

Flow cytometry as an analytical method of drug-induced apoptosis in 3D bioprinted melanoma cells

Villiers

Plessis

2023

Biomed. Mater.

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Three-dimensional (3D) cell culture systems have gained increasing interest in drug discovery and tissue engineering due to its inherent advantages in providing more physiologically relevant information and more predictive data for in vivo tests. Along with the development of more physiologically relevant 3D cell culture models, researchers bear the responsibility to validate new cell assay techniques capable of measuring and evaluating constructs that are physically larger and more complex compared to two- dimensional (2D) cell cultures. It is important to note that assays based on monolayer cultures may be insufficient for the use in 3D cell cultures models. In this study we firstly fabricated a 3D bioprinted hydrogel melanoma scaffold. This was used to validate a flow cytometry-based analytical method as a tool for 3D bioprinted structures to assess drug-induced apoptosis. The results indicated high robustness, reproducibility and sensitivity of the flow cytometric method established on the 3D cell-laden A375 melanoma hydrogel scaffolds. Over and above this, it was possible to determine the effect of etoposide on A375 melanoma cells using Annexin V and PI apoptosis assay.

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“…In this regard, the solution could be to develop an engineered human tissue as a gold standard model to study the inflammatory and inhibitory processes derived from HIV‐1 infection. In other words, a single explant model that can recapitulate mucosal cell diversity, immune response, and inter‐donor variation (Herrera, 2019).…”

Section: Ex Vivo Preclinical Studiesmentioning

confidence: 99%

Baseline and time‐updated factors in preclinical development of anionic dendrimers as successful anti‐HIV‐1 vaginal microbicides

Rodriguez-Izquierdo

Sepúlveda‐Crespo

Lasso³

et al. 2022

WIREs Nanomed Nanobiotechnol

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Although a wide variety of topical microbicides provide promising in vitro and in vivo efficacy, most of them failed to prevent sexual transmission of human immunodeficiency virus type 1 (HIV-1) in human clinical trials. In vitro, ex vivo, and in vivo models must be optimized, considering the knowledge acquired from unsuccessful and successful clinical trials to improve the current gaps and the preclinical development protocols. To date, dendrimers are the only nanotool that has advanced to human clinical trials as topical microbicides to prevent HIV-1 transmission. This fact demonstrates the importance and the potential of these molecules as microbicides. Polyanionic dendrimers

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The Pre-clinical Toolbox of Pharmacokinetics and Pharmacodynamics: in vitro and ex vivo Models

Cited by 6 publications

References 183 publications

Evaluation of the novel vaginal contraceptive agent PPCM in preclinical studies using sperm hyaluronan binding and acrosome status assays

Evaluation of the novel vaginal contraceptive agent PPCM in preclinical studies using sperm hyaluronan binding and acrosome status assays

Flow cytometry as an analytical method of drug-induced apoptosis in 3D bioprinted melanoma cells

Baseline and time‐updated factors in preclinical development of anionic dendrimers as successful anti‐HIV‐1 vaginal microbicides

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