Development and evaluation of a thermosensitive vaginal gel containing raltegravir+efavirenz loaded nanoparticles for HIV prophylaxis

Abhijit A. Date, Annemarie Shibata, Michael Goede, Bridget Sanford, Krista La Bruzzo, Michael A. Belshan, Christopher J. Destache

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The objective of this investigation was to develop a thermosensitive vaginal gel containing raltegravir+efavirenz loaded PLGA nanoparticles (RAL+EFV-NPs) for pre-exposure prophylaxis of HIV. RAL+EFV-NPs were fabricated using a modified emulsion-solvent evaporation method and characterized for size and zeta potential. The average size and surface charge of RAL+EFV-NP were 81.8±6.4nm and -23.18±7.18mV respectively. The average encapsulation efficiency of raltegravir and efavirenz was 55.5% and 98.2% respectively. Thermosensitive vaginal gel containing RAL+EFV-NPs was successfully prepared using a combination of Pluronic F127 (20% w/v) and Pluronic F68 (1% w/v). Incorporation RAL+EFV-NPs in the gel did not result in nanoparticle aggregation and RAL+EFV-NPs containing gel showed thermogelation at 32.5°C. The RAL+EFV-NPs were evaluated for inhibition of HIV-1NL4-3 using TZM-bl indicator cells. The EC90 of RAL+EFV-NPs was lower than raltegravir+efavirenz (RAL+EFV) solution but did not reach significance. Compared to control HeLa cells without any treatment, RAL+EFV-NPs or blank gel were not cytotoxic for 14days in vitro. The intracellular levels of efavirenz in RAL+EFV-NPs treated HeLa cells were above the EC90 for 14days whereas raltegravir intracellular concentrations were eliminated within 6days. Transwell experiments of NPs-in-gel demonstrated rapid transfer of fluorescent nanoparticles from the gel and uptake in HeLa cells within 30min. These data demonstrate the potential of antiretroviral NP-embedded vagina gels for long-term vaginal pre-exposure prophylaxis of heterosexual HIV-1 transmission.

Original languageEnglish
Pages (from-to)430-436
Number of pages7
JournalAntiviral Research
Volume96
Issue number3
DOIs
StatePublished - Dec 2012

Fingerprint

efavirenz
Foams and Jellies Vaginal Creams
Nanoparticles
HIV
Gels
HeLa Cells
Poloxamer
UCON 50-HB-5100
Raltegravir Potassium

All Science Journal Classification (ASJC) codes

  • Virology
  • Pharmacology

Cite this

Development and evaluation of a thermosensitive vaginal gel containing raltegravir+efavirenz loaded nanoparticles for HIV prophylaxis. / Date, Abhijit A.; Shibata, Annemarie; Goede, Michael; Sanford, Bridget; La Bruzzo, Krista; Belshan, Michael A.; Destache, Christopher J.

In: Antiviral Research, Vol. 96, No. 3, 12.2012, p. 430-436.

Research output: Contribution to journalArticle

@article{761c677025044406be5973e79b4bf083,
title = "Development and evaluation of a thermosensitive vaginal gel containing raltegravir+efavirenz loaded nanoparticles for HIV prophylaxis",
abstract = "The objective of this investigation was to develop a thermosensitive vaginal gel containing raltegravir+efavirenz loaded PLGA nanoparticles (RAL+EFV-NPs) for pre-exposure prophylaxis of HIV. RAL+EFV-NPs were fabricated using a modified emulsion-solvent evaporation method and characterized for size and zeta potential. The average size and surface charge of RAL+EFV-NP were 81.8±6.4nm and -23.18±7.18mV respectively. The average encapsulation efficiency of raltegravir and efavirenz was 55.5{\%} and 98.2{\%} respectively. Thermosensitive vaginal gel containing RAL+EFV-NPs was successfully prepared using a combination of Pluronic F127 (20{\%} w/v) and Pluronic F68 (1{\%} w/v). Incorporation RAL+EFV-NPs in the gel did not result in nanoparticle aggregation and RAL+EFV-NPs containing gel showed thermogelation at 32.5°C. The RAL+EFV-NPs were evaluated for inhibition of HIV-1NL4-3 using TZM-bl indicator cells. The EC90 of RAL+EFV-NPs was lower than raltegravir+efavirenz (RAL+EFV) solution but did not reach significance. Compared to control HeLa cells without any treatment, RAL+EFV-NPs or blank gel were not cytotoxic for 14days in vitro. The intracellular levels of efavirenz in RAL+EFV-NPs treated HeLa cells were above the EC90 for 14days whereas raltegravir intracellular concentrations were eliminated within 6days. Transwell experiments of NPs-in-gel demonstrated rapid transfer of fluorescent nanoparticles from the gel and uptake in HeLa cells within 30min. These data demonstrate the potential of antiretroviral NP-embedded vagina gels for long-term vaginal pre-exposure prophylaxis of heterosexual HIV-1 transmission.",
author = "Date, {Abhijit A.} and Annemarie Shibata and Michael Goede and Bridget Sanford and {La Bruzzo}, Krista and Belshan, {Michael A.} and Destache, {Christopher J.}",
year = "2012",
month = "12",
doi = "10.1016/j.antiviral.2012.09.015",
language = "English",
volume = "96",
pages = "430--436",
journal = "Antiviral Research",
issn = "0166-3542",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Development and evaluation of a thermosensitive vaginal gel containing raltegravir+efavirenz loaded nanoparticles for HIV prophylaxis

AU - Date, Abhijit A.

AU - Shibata, Annemarie

AU - Goede, Michael

AU - Sanford, Bridget

AU - La Bruzzo, Krista

AU - Belshan, Michael A.

AU - Destache, Christopher J.

PY - 2012/12

Y1 - 2012/12

N2 - The objective of this investigation was to develop a thermosensitive vaginal gel containing raltegravir+efavirenz loaded PLGA nanoparticles (RAL+EFV-NPs) for pre-exposure prophylaxis of HIV. RAL+EFV-NPs were fabricated using a modified emulsion-solvent evaporation method and characterized for size and zeta potential. The average size and surface charge of RAL+EFV-NP were 81.8±6.4nm and -23.18±7.18mV respectively. The average encapsulation efficiency of raltegravir and efavirenz was 55.5% and 98.2% respectively. Thermosensitive vaginal gel containing RAL+EFV-NPs was successfully prepared using a combination of Pluronic F127 (20% w/v) and Pluronic F68 (1% w/v). Incorporation RAL+EFV-NPs in the gel did not result in nanoparticle aggregation and RAL+EFV-NPs containing gel showed thermogelation at 32.5°C. The RAL+EFV-NPs were evaluated for inhibition of HIV-1NL4-3 using TZM-bl indicator cells. The EC90 of RAL+EFV-NPs was lower than raltegravir+efavirenz (RAL+EFV) solution but did not reach significance. Compared to control HeLa cells without any treatment, RAL+EFV-NPs or blank gel were not cytotoxic for 14days in vitro. The intracellular levels of efavirenz in RAL+EFV-NPs treated HeLa cells were above the EC90 for 14days whereas raltegravir intracellular concentrations were eliminated within 6days. Transwell experiments of NPs-in-gel demonstrated rapid transfer of fluorescent nanoparticles from the gel and uptake in HeLa cells within 30min. These data demonstrate the potential of antiretroviral NP-embedded vagina gels for long-term vaginal pre-exposure prophylaxis of heterosexual HIV-1 transmission.

AB - The objective of this investigation was to develop a thermosensitive vaginal gel containing raltegravir+efavirenz loaded PLGA nanoparticles (RAL+EFV-NPs) for pre-exposure prophylaxis of HIV. RAL+EFV-NPs were fabricated using a modified emulsion-solvent evaporation method and characterized for size and zeta potential. The average size and surface charge of RAL+EFV-NP were 81.8±6.4nm and -23.18±7.18mV respectively. The average encapsulation efficiency of raltegravir and efavirenz was 55.5% and 98.2% respectively. Thermosensitive vaginal gel containing RAL+EFV-NPs was successfully prepared using a combination of Pluronic F127 (20% w/v) and Pluronic F68 (1% w/v). Incorporation RAL+EFV-NPs in the gel did not result in nanoparticle aggregation and RAL+EFV-NPs containing gel showed thermogelation at 32.5°C. The RAL+EFV-NPs were evaluated for inhibition of HIV-1NL4-3 using TZM-bl indicator cells. The EC90 of RAL+EFV-NPs was lower than raltegravir+efavirenz (RAL+EFV) solution but did not reach significance. Compared to control HeLa cells without any treatment, RAL+EFV-NPs or blank gel were not cytotoxic for 14days in vitro. The intracellular levels of efavirenz in RAL+EFV-NPs treated HeLa cells were above the EC90 for 14days whereas raltegravir intracellular concentrations were eliminated within 6days. Transwell experiments of NPs-in-gel demonstrated rapid transfer of fluorescent nanoparticles from the gel and uptake in HeLa cells within 30min. These data demonstrate the potential of antiretroviral NP-embedded vagina gels for long-term vaginal pre-exposure prophylaxis of heterosexual HIV-1 transmission.

UR - http://www.scopus.com/inward/record.url?scp=84869212370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84869212370&partnerID=8YFLogxK

U2 - 10.1016/j.antiviral.2012.09.015

DO - 10.1016/j.antiviral.2012.09.015

M3 - Article

C2 - 23041201

AN - SCOPUS:84869212370

VL - 96

SP - 430

EP - 436

JO - Antiviral Research

JF - Antiviral Research

SN - 0166-3542

IS - 3

ER -