Development and validation of a HPLC method for the assay of dapivirine in cell-based and tissue permeability experiments

Neves, José das; Sarmento, Bruno; Amiji, Mansoor M.; Bahia, Maria Fernanda

doi:10.1016/j.jchromb.2012.10.034

Cited by 11 publications

(14 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although circulating plasma levels of topically administered dapivirine are low, the described LC–MS/MS method is being used in several clinical studies and is sensitive enough to detect plasma dapivirine following topical microbicide dosing. Many of the previously published methods are unable to reach the LLOQ described herein [18,20,27,32]. Therefore, this method may be applied for the quantification of plasma dapivirine levels in clinical trials from a variety of topical formulations.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, highly sensitive methods are required to quantitate plasma dapivirine concentrations. Previous approaches for the detection and quantification of dapivirine from pharmacological delivery systems and biological matrices include HPLC–UV and LC–MS/MS analyses [17,27,28]. In contrast to previously published approaches, the LC–MS/MS method described herein offers several key advantages; including rapid, low-cost sample preparation and robust UHPLC–MS/MS analysis, as well as increased sensitivity when compared with existing HPLC–UV methods.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Development and Validation of an UHPLC–MS/MS Method for The Rapid Quantification of The Antiretroviral Agent Dapivirine in Human Plasma

et al. 2013

View full text Add to dashboard Cite

Background Dapivirine is a non-nucleoside reverse transcriptase inhibitor designed to prevent HIV-1 viral replication and subsequent propagation. A sensitive method is required to quantify plasma concentrations to assess drug efficacy. Results Dapivirine-spiked plasma was combined with acetonitrile containing deuterated IS and was processed for analysis. The method has an analytical measuring range from 20 to 10,000 pg/ml. For the LLOQ, low, mid and high QCs, intra- and inter-assay precision (%CV) ranged from 5.58 to 13.89% and 5.23 to 13.36%, respectively, and intra- and inter-day accuracy (% deviation) ranged from -5.61 to 0.75% and -4.30 to 6.24%, respectively. Conclusion A robust and sensitive LC–MS/MS assay for the high-throughput quantification of the antiretroviral drug dapivirine in human plasma was developed and validated following bioanalytical validation guidelines. The assay meets criteria for the analysis of samples from large research trials.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Development and Validation of an UHPLC–MS/MS Method for The Rapid Quantification of The Antiretroviral Agent Dapivirine in Human Plasma

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Dapivirine was determined from the supernatants by HPLC-UV. 27 All conditions were performed in triplicate in three different experiments. Cell viability at the maximum time of incubation (6 h) and maximum concentration (10 μM) used was assessed using a commercially available kit (CellTiter 96 AQueous One Solution Cell Proliferation Assay, Promega, Madison, WI, USA) based on the bioreduction of a tetrazolium derivative (MTS) by metabolically active cells, further referred to as MTS assay.…”

Section: Preparation Of Rhodamine-123-labeled Poly(ε-caprolactonementioning

confidence: 99%

In Vitro and Ex Vivo Evaluation of Polymeric Nanoparticles for Vaginal and Rectal Delivery of the Anti-HIV Drug Dapivirine

Neves

Araújo²,

Andrade

et al. 2013

Mol. Pharmaceutics

Self Cite

View full text Add to dashboard Cite

Prevention strategies such as the development of microbicides are thought to be valuable in the fight against HIV/AIDS. Despite recent achievements, there is still a long road ahead in the field, particularly at the level of drug formulation. Drug nanocarriers based on polymers may be useful in enhancing local drug delivery while limiting systemic exposure. We prepared differently surface-engineered poly(ε-caprolactone) (PCL) nanoparticles (NPs) and tested their ability to modulate the permeability and retention of dapivirine in cell monolayers and pig vaginal and rectal mucosa. NPs coated with poly(ethylene oxide) (PEO) were shown able to reduce permeability across monolayers/tissues, while modification of nanosystems with cetyl trimethylammonium bromide (CTAB) enhanced transport. In the case of coating NPs with sodium lauryl sulfate (SLS), dapivirine permeability was unchanged. All NPs increased monolayer/tissue drug retention as compared to unformulated dapivirine. This fact was associated, at least partially, to the ability of NPs to be taken up by cells or penetrate mucosal tissue. Cell and tissue toxicity was also affected differently by NPs: PEO modification decreased the in vitro (but not ex vivo) toxicity of dapivirine, while higher toxicity was generally observed for NPs coated with SLS or CTAB. Overall, presented results support that PCL nanoparticles are capable of modulating drug permeability and retention in cell monolayers and mucosal tissues relevant for vaginal and rectal delivery of microbicides. In particular, PEO-modified dapivirine-loaded PCL NPs may be advantageous in increasing drug residence at epithelial cell lines/mucosal tissues, which may potentially increase the efficacy of microbicide drugs.

show abstract

“…All PCL NPs were shown to be taken up in vitro by multiple cell types relevant to vaginal HIV transmission/vaginal microbicide development and, in order to assess any real value of such behavior, intracellular/cell associated dapivirine levels were further determined ( Figure 7A) [87,115,118]. It was apparent that NPs could significantly increase the intracellular/cell associated drug levels in the case of immune cells (peripheral blood mononuclear cells, macrophages and dendritic cells) as compared to pure dapivirine in suspension, while there was a trend for similar values when cells of vaginal (and rectal) epithelial origin were used.…”

Section: Prevention Of Hiv Transmissionmentioning

confidence: 99%

Polymer-based nanocarriers for vaginal drug delivery

Neves

Nunes

Machado

et al. 2015

Advanced Drug Delivery Reviews

Self Cite

117

View full text Add to dashboard Cite

The vaginal delivery of various drugs is well described and its relevance established in current medical practice. Alongside recent advances and achievements in the fields of pharmaceutical nanotechnology and nanomedicine, there is an increasing interest in the potential use of different nanocarriers for the delivery of old and new pharmacologically active molecules with either therapeutic or prophylactic purposes. Nanosystems of polymeric nature in particular have been investigated over the last years and their interactions with mucosal fluids and tissues, as well as genital tract biodistribution upon vaginal administration, are now better understood. While different applications have been envisioned, most of the current research is focusing in the development of nano-formulations with the potential to inhibit the vaginal transmission of HIV upon sexual intercourse. The present work focuses its discussion on the potential and perils of polymer-based nanocarriers for the vaginal administration of different pharmacologically active molecules.

show abstract

Development and validation of a HPLC method for the assay of dapivirine in cell-based and tissue permeability experiments

Cited by 11 publications

References 32 publications

The Development and Validation of an UHPLC–MS/MS Method for The Rapid Quantification of The Antiretroviral Agent Dapivirine in Human Plasma

The Development and Validation of an UHPLC–MS/MS Method for The Rapid Quantification of The Antiretroviral Agent Dapivirine in Human Plasma

In Vitro and Ex Vivo Evaluation of Polymeric Nanoparticles for Vaginal and Rectal Delivery of the Anti-HIV Drug Dapivirine

Polymer-based nanocarriers for vaginal drug delivery

Contact Info

Product

Resources

About