Locally administered nanosuspension increases delivery of estradiol for the treatment of vaginal atrophy in mice

Rachel L Shapiro; Titania Bethiana; Davell M Carter; Jairo Ortiz; Kevin DeLong; Nicole Anders; Tricia A Numan; Eliza Duggan; Hannah C Zierden; Laura M Ensign

doi:10.1007/s13346-024-01618-6

Locally administered nanosuspension increases delivery of estradiol for the treatment of vaginal atrophy in mice

Drug Deliv Transl Res. 2024 May 15. doi: 10.1007/s13346-024-01618-6. Online ahead of print.

Authors

Rachel L Shapiro^{1

2}, Titania Bethiana^{1

2}, Davell M Carter^{2

3}, Jairo Ortiz^{2

4}, Kevin DeLong^{2

4}, Nicole Anders⁵, Tricia A Numan⁶, Eliza Duggan^{1

2}, Hannah C Zierden⁷, Laura M Ensign^{8

9

10

11

12

13}

Affiliations

¹ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD, 21218, USA.
² The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
³ Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
⁴ Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
⁵ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
⁶ Department of Pathology, Sibley Memorial Hospital, Johns Hopkins University School of Medicine, Washington, DC, 20016, USA.
⁷ Department of Chemical and Biomolecular Engineering, University of Maryland College Park, College Park, MD, 20742, USA. hzierden@umd.edu.
⁸ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD, 21218, USA. lensign@jhmi.edu.
⁹ The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA. lensign@jhmi.edu.
¹⁰ Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. lensign@jhmi.edu.
¹¹ Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA. lensign@jhmi.edu.
¹² Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA. lensign@jhmi.edu.
¹³ Department of Gynecology and Obstetrics, Department of Biomedical Engineering, and Department of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. lensign@jhmi.edu.

PMID: 38748201
DOI: 10.1007/s13346-024-01618-6

Abstract

Vaginal atrophy affects up to 57% of post-menopausal women, with symptoms ranging from vaginal burning to dysuria. Estradiol hormone replacement therapy may be prescribed to alleviate these symptoms, though many vaginal products have drawbacks including increased discharge and local tissue toxicity due to their hypertonic nature. Here, we describe the development and characterization of a Pluronic F127-coated estradiol nanosuspension (NS) formulation for improved vaginal estradiol delivery. We compare the pharmacokinetics to the clinical comparator vaginal cream (Estrace) and demonstrate increased delivery of estradiol to the vaginal tissue. We utilized ovariectomized (OVX) mice as a murine model of post-menopausal vaginal atrophy and demonstrated equivalent efficacy in vaginal re-epithelialization when dosed with either the estradiol NS or Estrace cream. Further, we demonstrate compatibility of the estradiol NS with vaginal bacteria in vitro. We demonstrate that a Pluronic F127-coated estradiol NS may be a viable option for the treatment of post-menopausal vaginal atrophy.

Keywords: Estradiol; Menopause; Nanosuspension; Vaginal atrophy; Vaginal drug delivery.

Abstract

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