A vaginal nanoformulation of a SphK inhibitor attenuates lipopolysaccharide-induced preterm birth in mice

Kiersten Giusto; Manali Patki; Jagadish Koya; Charles R. Ashby; Swapna Munnangi; Ketan Patel; Sandra E. Reznik

doi:10.2217/nnm-2019-0243

A vaginal nanoformulation of a SphK inhibitor attenuates lipopolysaccharide-induced preterm birth in mice

Kiersten Giusto, Manali Patki, Jagadish Koya, Charles R. Ashby, Swapna Munnangi, Ketan Patel, Sandra E. Reznik

Pathology

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Aim: Previously, we have shown that inhibition of SphK by the SphK inhibitor-II (SKI II) prevents lipopolysaccharide-induced preterm birth in mice. The aim of this study was to develop a vaginal self-nanoemulsifying drug-delivery system (SNEDDS) for SKI II. Materials & methods: A SKI II-loaded SNEDDS was characterized and tested in a murine preterm birth model. Results: The SNEDDS immediately formed a gel and then slowly emulsified to nanoglobules with over 500-fold enhancement of SKI II solubility at vaginal pH. Intravaginal administration of the SKI II SNEDDS significantly decreased lipopolysaccharide-induced preterm birth in mice. Conclusion: A vaginal nanoformulation of SKI II represents a novel, noninvasive approach to prevent preterm birth.

Original language	English (US)
Pages (from-to)	2835-2851
Number of pages	17
Journal	Nanomedicine
Volume	14
Issue number	21
DOIs	https://doi.org/10.2217/nnm-2019-0243
State	Published - 2019

Keywords

SKI II
SNEDDS
inflammation
lipopolysaccharide
nanoformulation
preterm birth
sphingosine kinase inhibitor
vaginal administration

ASJC Scopus subject areas

Bioengineering
Medicine (miscellaneous)
Biomedical Engineering
Materials Science(all)

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10.2217/nnm-2019-0243

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title = "A vaginal nanoformulation of a SphK inhibitor attenuates lipopolysaccharide-induced preterm birth in mice",

abstract = "Aim: Previously, we have shown that inhibition of SphK by the SphK inhibitor-II (SKI II) prevents lipopolysaccharide-induced preterm birth in mice. The aim of this study was to develop a vaginal self-nanoemulsifying drug-delivery system (SNEDDS) for SKI II. Materials & methods: A SKI II-loaded SNEDDS was characterized and tested in a murine preterm birth model. Results: The SNEDDS immediately formed a gel and then slowly emulsified to nanoglobules with over 500-fold enhancement of SKI II solubility at vaginal pH. Intravaginal administration of the SKI II SNEDDS significantly decreased lipopolysaccharide-induced preterm birth in mice. Conclusion: A vaginal nanoformulation of SKI II represents a novel, noninvasive approach to prevent preterm birth.",

keywords = "SKI II, SNEDDS, inflammation, lipopolysaccharide, nanoformulation, preterm birth, sphingosine kinase inhibitor, vaginal administration",

author = "Kiersten Giusto and Manali Patki and Jagadish Koya and Ashby, {Charles R.} and Swapna Munnangi and Ketan Patel and Reznik, {Sandra E.}",

note = "Funding Information: SE Reznik received funding from a Nassau Health Care Corporation Grant (FY2016-2019) and a St John{\textquoteright}s University Seed Grant (FY2015-16). SE Reznik and CR Ashby have submitted a patent application on the use of SphK inhibitor II for preterm birth. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: {\textcopyright} 2019 Future Medicine Ltd.",

year = "2019",

doi = "10.2217/nnm-2019-0243",

language = "English (US)",

volume = "14",

pages = "2835--2851",

journal = "Nanomedicine",

issn = "1743-5889",

publisher = "Future Medicine Ltd.",

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T1 - A vaginal nanoformulation of a SphK inhibitor attenuates lipopolysaccharide-induced preterm birth in mice

AU - Giusto, Kiersten

AU - Patki, Manali

AU - Koya, Jagadish

AU - Ashby, Charles R.

AU - Munnangi, Swapna

AU - Patel, Ketan

AU - Reznik, Sandra E.

N1 - Funding Information: SE Reznik received funding from a Nassau Health Care Corporation Grant (FY2016-2019) and a St John’s University Seed Grant (FY2015-16). SE Reznik and CR Ashby have submitted a patent application on the use of SphK inhibitor II for preterm birth. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: © 2019 Future Medicine Ltd.

PY - 2019

Y1 - 2019

N2 - Aim: Previously, we have shown that inhibition of SphK by the SphK inhibitor-II (SKI II) prevents lipopolysaccharide-induced preterm birth in mice. The aim of this study was to develop a vaginal self-nanoemulsifying drug-delivery system (SNEDDS) for SKI II. Materials & methods: A SKI II-loaded SNEDDS was characterized and tested in a murine preterm birth model. Results: The SNEDDS immediately formed a gel and then slowly emulsified to nanoglobules with over 500-fold enhancement of SKI II solubility at vaginal pH. Intravaginal administration of the SKI II SNEDDS significantly decreased lipopolysaccharide-induced preterm birth in mice. Conclusion: A vaginal nanoformulation of SKI II represents a novel, noninvasive approach to prevent preterm birth.

AB - Aim: Previously, we have shown that inhibition of SphK by the SphK inhibitor-II (SKI II) prevents lipopolysaccharide-induced preterm birth in mice. The aim of this study was to develop a vaginal self-nanoemulsifying drug-delivery system (SNEDDS) for SKI II. Materials & methods: A SKI II-loaded SNEDDS was characterized and tested in a murine preterm birth model. Results: The SNEDDS immediately formed a gel and then slowly emulsified to nanoglobules with over 500-fold enhancement of SKI II solubility at vaginal pH. Intravaginal administration of the SKI II SNEDDS significantly decreased lipopolysaccharide-induced preterm birth in mice. Conclusion: A vaginal nanoformulation of SKI II represents a novel, noninvasive approach to prevent preterm birth.

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KW - sphingosine kinase inhibitor

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A vaginal nanoformulation of a SphK inhibitor attenuates lipopolysaccharide-induced preterm birth in mice

Abstract

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