Combining a synthetic spermicide with a natural trichomonacide for safe, prophylactic contraception

Ashish Jain, Lokesh Kumar, Bhavana Kushwaha, Monika Sharma, Aastha Pandey, Vikas Verma, Vikas Sharma, Vishal Singh, Tara Rawat, Vishnu L. Sharma, Jagdamba P. Maikhuri, Gopal Gupta

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

STUDY QUESTIONCan a specifically acting synthetic spermicide (DSE-37) be combined with a natural microbicide (saponins) for safe, prophylactic contraception?SUMMARY ANSWERA 1:1 (w/w) combination of DSE-37 and Sapindus saponins can target sperm and Trichomonas vaginalis precisely without any noticeable off-target effects on somatic cells at effective concentrations.WHAT IS KNOWN ALREADYBroad-spectrum vaginal agents like nonoxynol-9 (N-9) and cellulose sulfate have failed clinically as microbicides due to non-specific off-target effects, whereas agents that specifically target retroviruses have shown promise in clinical trials. DSE-37 and Sapindus saponins, respectively, specifically target human sperm and T. vaginalis in vitro.STUDY DESIGN, SIZE, DURATIONA comprehensive study of efficacy and safety was undertaken using in vitro (human cells) and in vivo (rabbit) models. The 1:1 combination of DSE-37 and Sapindus saponins was based on the in vitro spermicidal and anti-Trichomonal activities of the two components. N-9, the spermicide in clinical use, served as reference control. Free sperm thiols were fluorescently glinted to reveal differences in the targets of the test agents.PARTICIPANTS/MATERIALS, SETTING, METHODSOn/off-target effects were evaluated in vitro against human sperm, T. vaginalis, HeLa, Vk2/E6E7, End1/E6E7 and Lactobacillus jensenii, using standard assays of drug susceptibility, cell viability, flow cytometric assessment of cell apoptosis and qPCR for expression of pro-inflammatory cytokine mRNAs. The spermicidal effect was also recorded live and free thiols on sperm were fluorescently visualized using a commercial kit. In vivo contraceptive efficacy (pregnancy/fertility rates) and safety (vaginal histopathology and in situ immune-labeling of inflammation markers VCAM-1, E-selectin and NFkB) were evaluated in rabbits.MAIN RESULTS AND THE ROLE OF CHANCEA 0.003% drug 'combination' containing 0.0015% each of DSE-37 and Sapindus saponins in physiological saline irreversibly immobilized 100% human sperm in ∼30 s and eliminated 100% T. vaginalis in 24 h, without causing any detectable toxicity to human cervical (HeLa) cells and Lactobacilli in 24-48 h, in vitro. N-9 at 0.003% exhibited lower microbicidal activity against Trichomonas but failed in spermicidal assays while causing severe toxicity to HeLa cells and Lactobacilli in 12-24 h. The 'combination' of DSE-37 and Sapindus saponins completely prevented pregnancy in rabbits at a vaginal dose of 20 mg (1% in K-Y Jelly), while application of 5% 'combination' in K-Y Jelly for 4 consecutive days caused negligible alterations in epithelial lining of rabbit vagina with only minor changes in levels of inflammation markers. N-9 at a 20 mg vaginal dose prevented pregnancy in 33% animals and a 4-day repeat application of 2% N-9 gel caused severe local toxicity to vaginal epithelium with molecular expression of acute inflammation markers.LIMITATIONS, REASONS FOR CAUTIONThe number of animals used for the in vivo efficacy study was limited by the approval of the animal ethics committee.WIDER IMPLICATIONS OF THE FINDINGSAnti-Trichomonal contraceptives with specifically acting synthetic component and clinically-proven safe natural component may define a new concept in empowering women to control their fertility and reproductive health.STUDY FUNDING/COMPETING INTEREST(S)The study was funded by CSIR-Network Project 'PROGRAM' (BSC0101) and partly by the Ministry of Health and Family Welfare, Government of India (GAP0001). The funding agencies did not play any role in this study and none of the authors had any competing interest(s).

Original languageEnglish (US)
Pages (from-to)242-252
Number of pages11
JournalHuman Reproduction
Volume29
Issue number2
DOIs
StatePublished - Feb 2014

Fingerprint

Sapindus
Saponins
Contraception
Spermatozoa
Trichomonas vaginalis
Lactobacillus
Rabbits
Contraceptive Agents
Anti-Infective Agents
Inflammation
HeLa Cells
Sulfhydryl Compounds
Nonoxynol
Animal Care Committees
Trichomonas
Safety
Pregnancy
E-Selectin
Vascular Cell Adhesion Molecule-1
Family Health

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Jain, A., Kumar, L., Kushwaha, B., Sharma, M., Pandey, A., Verma, V., ... Gupta, G. (2014). Combining a synthetic spermicide with a natural trichomonacide for safe, prophylactic contraception. Human Reproduction, 29(2), 242-252. https://doi.org/10.1093/humrep/det423
Jain, Ashish ; Kumar, Lokesh ; Kushwaha, Bhavana ; Sharma, Monika ; Pandey, Aastha ; Verma, Vikas ; Sharma, Vikas ; Singh, Vishal ; Rawat, Tara ; Sharma, Vishnu L. ; Maikhuri, Jagdamba P. ; Gupta, Gopal. / Combining a synthetic spermicide with a natural trichomonacide for safe, prophylactic contraception. In: Human Reproduction. 2014 ; Vol. 29, No. 2. pp. 242-252.
@article{f003cd2f4233443f83127b503cb5b94e,
title = "Combining a synthetic spermicide with a natural trichomonacide for safe, prophylactic contraception",
abstract = "STUDY QUESTIONCan a specifically acting synthetic spermicide (DSE-37) be combined with a natural microbicide (saponins) for safe, prophylactic contraception?SUMMARY ANSWERA 1:1 (w/w) combination of DSE-37 and Sapindus saponins can target sperm and Trichomonas vaginalis precisely without any noticeable off-target effects on somatic cells at effective concentrations.WHAT IS KNOWN ALREADYBroad-spectrum vaginal agents like nonoxynol-9 (N-9) and cellulose sulfate have failed clinically as microbicides due to non-specific off-target effects, whereas agents that specifically target retroviruses have shown promise in clinical trials. DSE-37 and Sapindus saponins, respectively, specifically target human sperm and T. vaginalis in vitro.STUDY DESIGN, SIZE, DURATIONA comprehensive study of efficacy and safety was undertaken using in vitro (human cells) and in vivo (rabbit) models. The 1:1 combination of DSE-37 and Sapindus saponins was based on the in vitro spermicidal and anti-Trichomonal activities of the two components. N-9, the spermicide in clinical use, served as reference control. Free sperm thiols were fluorescently glinted to reveal differences in the targets of the test agents.PARTICIPANTS/MATERIALS, SETTING, METHODSOn/off-target effects were evaluated in vitro against human sperm, T. vaginalis, HeLa, Vk2/E6E7, End1/E6E7 and Lactobacillus jensenii, using standard assays of drug susceptibility, cell viability, flow cytometric assessment of cell apoptosis and qPCR for expression of pro-inflammatory cytokine mRNAs. The spermicidal effect was also recorded live and free thiols on sperm were fluorescently visualized using a commercial kit. In vivo contraceptive efficacy (pregnancy/fertility rates) and safety (vaginal histopathology and in situ immune-labeling of inflammation markers VCAM-1, E-selectin and NFkB) were evaluated in rabbits.MAIN RESULTS AND THE ROLE OF CHANCEA 0.003{\%} drug 'combination' containing 0.0015{\%} each of DSE-37 and Sapindus saponins in physiological saline irreversibly immobilized 100{\%} human sperm in ∼30 s and eliminated 100{\%} T. vaginalis in 24 h, without causing any detectable toxicity to human cervical (HeLa) cells and Lactobacilli in 24-48 h, in vitro. N-9 at 0.003{\%} exhibited lower microbicidal activity against Trichomonas but failed in spermicidal assays while causing severe toxicity to HeLa cells and Lactobacilli in 12-24 h. The 'combination' of DSE-37 and Sapindus saponins completely prevented pregnancy in rabbits at a vaginal dose of 20 mg (1{\%} in K-Y Jelly), while application of 5{\%} 'combination' in K-Y Jelly for 4 consecutive days caused negligible alterations in epithelial lining of rabbit vagina with only minor changes in levels of inflammation markers. N-9 at a 20 mg vaginal dose prevented pregnancy in 33{\%} animals and a 4-day repeat application of 2{\%} N-9 gel caused severe local toxicity to vaginal epithelium with molecular expression of acute inflammation markers.LIMITATIONS, REASONS FOR CAUTIONThe number of animals used for the in vivo efficacy study was limited by the approval of the animal ethics committee.WIDER IMPLICATIONS OF THE FINDINGSAnti-Trichomonal contraceptives with specifically acting synthetic component and clinically-proven safe natural component may define a new concept in empowering women to control their fertility and reproductive health.STUDY FUNDING/COMPETING INTEREST(S)The study was funded by CSIR-Network Project 'PROGRAM' (BSC0101) and partly by the Ministry of Health and Family Welfare, Government of India (GAP0001). The funding agencies did not play any role in this study and none of the authors had any competing interest(s).",
author = "Ashish Jain and Lokesh Kumar and Bhavana Kushwaha and Monika Sharma and Aastha Pandey and Vikas Verma and Vikas Sharma and Vishal Singh and Tara Rawat and Sharma, {Vishnu L.} and Maikhuri, {Jagdamba P.} and Gopal Gupta",
year = "2014",
month = "2",
doi = "10.1093/humrep/det423",
language = "English (US)",
volume = "29",
pages = "242--252",
journal = "Human Reproduction",
issn = "0268-1161",
publisher = "Oxford University Press",
number = "2",

}

Jain, A, Kumar, L, Kushwaha, B, Sharma, M, Pandey, A, Verma, V, Sharma, V, Singh, V, Rawat, T, Sharma, VL, Maikhuri, JP & Gupta, G 2014, 'Combining a synthetic spermicide with a natural trichomonacide for safe, prophylactic contraception', Human Reproduction, vol. 29, no. 2, pp. 242-252. https://doi.org/10.1093/humrep/det423

Combining a synthetic spermicide with a natural trichomonacide for safe, prophylactic contraception. / Jain, Ashish; Kumar, Lokesh; Kushwaha, Bhavana; Sharma, Monika; Pandey, Aastha; Verma, Vikas; Sharma, Vikas; Singh, Vishal; Rawat, Tara; Sharma, Vishnu L.; Maikhuri, Jagdamba P.; Gupta, Gopal.

In: Human Reproduction, Vol. 29, No. 2, 02.2014, p. 242-252.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Combining a synthetic spermicide with a natural trichomonacide for safe, prophylactic contraception

AU - Jain, Ashish

AU - Kumar, Lokesh

AU - Kushwaha, Bhavana

AU - Sharma, Monika

AU - Pandey, Aastha

AU - Verma, Vikas

AU - Sharma, Vikas

AU - Singh, Vishal

AU - Rawat, Tara

AU - Sharma, Vishnu L.

AU - Maikhuri, Jagdamba P.

AU - Gupta, Gopal

PY - 2014/2

Y1 - 2014/2

N2 - STUDY QUESTIONCan a specifically acting synthetic spermicide (DSE-37) be combined with a natural microbicide (saponins) for safe, prophylactic contraception?SUMMARY ANSWERA 1:1 (w/w) combination of DSE-37 and Sapindus saponins can target sperm and Trichomonas vaginalis precisely without any noticeable off-target effects on somatic cells at effective concentrations.WHAT IS KNOWN ALREADYBroad-spectrum vaginal agents like nonoxynol-9 (N-9) and cellulose sulfate have failed clinically as microbicides due to non-specific off-target effects, whereas agents that specifically target retroviruses have shown promise in clinical trials. DSE-37 and Sapindus saponins, respectively, specifically target human sperm and T. vaginalis in vitro.STUDY DESIGN, SIZE, DURATIONA comprehensive study of efficacy and safety was undertaken using in vitro (human cells) and in vivo (rabbit) models. The 1:1 combination of DSE-37 and Sapindus saponins was based on the in vitro spermicidal and anti-Trichomonal activities of the two components. N-9, the spermicide in clinical use, served as reference control. Free sperm thiols were fluorescently glinted to reveal differences in the targets of the test agents.PARTICIPANTS/MATERIALS, SETTING, METHODSOn/off-target effects were evaluated in vitro against human sperm, T. vaginalis, HeLa, Vk2/E6E7, End1/E6E7 and Lactobacillus jensenii, using standard assays of drug susceptibility, cell viability, flow cytometric assessment of cell apoptosis and qPCR for expression of pro-inflammatory cytokine mRNAs. The spermicidal effect was also recorded live and free thiols on sperm were fluorescently visualized using a commercial kit. In vivo contraceptive efficacy (pregnancy/fertility rates) and safety (vaginal histopathology and in situ immune-labeling of inflammation markers VCAM-1, E-selectin and NFkB) were evaluated in rabbits.MAIN RESULTS AND THE ROLE OF CHANCEA 0.003% drug 'combination' containing 0.0015% each of DSE-37 and Sapindus saponins in physiological saline irreversibly immobilized 100% human sperm in ∼30 s and eliminated 100% T. vaginalis in 24 h, without causing any detectable toxicity to human cervical (HeLa) cells and Lactobacilli in 24-48 h, in vitro. N-9 at 0.003% exhibited lower microbicidal activity against Trichomonas but failed in spermicidal assays while causing severe toxicity to HeLa cells and Lactobacilli in 12-24 h. The 'combination' of DSE-37 and Sapindus saponins completely prevented pregnancy in rabbits at a vaginal dose of 20 mg (1% in K-Y Jelly), while application of 5% 'combination' in K-Y Jelly for 4 consecutive days caused negligible alterations in epithelial lining of rabbit vagina with only minor changes in levels of inflammation markers. N-9 at a 20 mg vaginal dose prevented pregnancy in 33% animals and a 4-day repeat application of 2% N-9 gel caused severe local toxicity to vaginal epithelium with molecular expression of acute inflammation markers.LIMITATIONS, REASONS FOR CAUTIONThe number of animals used for the in vivo efficacy study was limited by the approval of the animal ethics committee.WIDER IMPLICATIONS OF THE FINDINGSAnti-Trichomonal contraceptives with specifically acting synthetic component and clinically-proven safe natural component may define a new concept in empowering women to control their fertility and reproductive health.STUDY FUNDING/COMPETING INTEREST(S)The study was funded by CSIR-Network Project 'PROGRAM' (BSC0101) and partly by the Ministry of Health and Family Welfare, Government of India (GAP0001). The funding agencies did not play any role in this study and none of the authors had any competing interest(s).

AB - STUDY QUESTIONCan a specifically acting synthetic spermicide (DSE-37) be combined with a natural microbicide (saponins) for safe, prophylactic contraception?SUMMARY ANSWERA 1:1 (w/w) combination of DSE-37 and Sapindus saponins can target sperm and Trichomonas vaginalis precisely without any noticeable off-target effects on somatic cells at effective concentrations.WHAT IS KNOWN ALREADYBroad-spectrum vaginal agents like nonoxynol-9 (N-9) and cellulose sulfate have failed clinically as microbicides due to non-specific off-target effects, whereas agents that specifically target retroviruses have shown promise in clinical trials. DSE-37 and Sapindus saponins, respectively, specifically target human sperm and T. vaginalis in vitro.STUDY DESIGN, SIZE, DURATIONA comprehensive study of efficacy and safety was undertaken using in vitro (human cells) and in vivo (rabbit) models. The 1:1 combination of DSE-37 and Sapindus saponins was based on the in vitro spermicidal and anti-Trichomonal activities of the two components. N-9, the spermicide in clinical use, served as reference control. Free sperm thiols were fluorescently glinted to reveal differences in the targets of the test agents.PARTICIPANTS/MATERIALS, SETTING, METHODSOn/off-target effects were evaluated in vitro against human sperm, T. vaginalis, HeLa, Vk2/E6E7, End1/E6E7 and Lactobacillus jensenii, using standard assays of drug susceptibility, cell viability, flow cytometric assessment of cell apoptosis and qPCR for expression of pro-inflammatory cytokine mRNAs. The spermicidal effect was also recorded live and free thiols on sperm were fluorescently visualized using a commercial kit. In vivo contraceptive efficacy (pregnancy/fertility rates) and safety (vaginal histopathology and in situ immune-labeling of inflammation markers VCAM-1, E-selectin and NFkB) were evaluated in rabbits.MAIN RESULTS AND THE ROLE OF CHANCEA 0.003% drug 'combination' containing 0.0015% each of DSE-37 and Sapindus saponins in physiological saline irreversibly immobilized 100% human sperm in ∼30 s and eliminated 100% T. vaginalis in 24 h, without causing any detectable toxicity to human cervical (HeLa) cells and Lactobacilli in 24-48 h, in vitro. N-9 at 0.003% exhibited lower microbicidal activity against Trichomonas but failed in spermicidal assays while causing severe toxicity to HeLa cells and Lactobacilli in 12-24 h. The 'combination' of DSE-37 and Sapindus saponins completely prevented pregnancy in rabbits at a vaginal dose of 20 mg (1% in K-Y Jelly), while application of 5% 'combination' in K-Y Jelly for 4 consecutive days caused negligible alterations in epithelial lining of rabbit vagina with only minor changes in levels of inflammation markers. N-9 at a 20 mg vaginal dose prevented pregnancy in 33% animals and a 4-day repeat application of 2% N-9 gel caused severe local toxicity to vaginal epithelium with molecular expression of acute inflammation markers.LIMITATIONS, REASONS FOR CAUTIONThe number of animals used for the in vivo efficacy study was limited by the approval of the animal ethics committee.WIDER IMPLICATIONS OF THE FINDINGSAnti-Trichomonal contraceptives with specifically acting synthetic component and clinically-proven safe natural component may define a new concept in empowering women to control their fertility and reproductive health.STUDY FUNDING/COMPETING INTEREST(S)The study was funded by CSIR-Network Project 'PROGRAM' (BSC0101) and partly by the Ministry of Health and Family Welfare, Government of India (GAP0001). The funding agencies did not play any role in this study and none of the authors had any competing interest(s).

UR - http://www.scopus.com/inward/record.url?scp=84893124820&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893124820&partnerID=8YFLogxK

U2 - 10.1093/humrep/det423

DO - 10.1093/humrep/det423

M3 - Article

C2 - 24291662

AN - SCOPUS:84893124820

VL - 29

SP - 242

EP - 252

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - 2

ER -