Mucus-penetrating PEGylated polysuccinimide-based nanocarrier for intravaginal delivery of siRNA battling sexually transmitted infections

Sarah Currie; Seungil Kim; Xiaochen Gu; Xiaoou Ren; Francis Lin; Shangxi Liu; Chengbo Yang; Ji-Heung Kim; Song Liu

doi:10.1016/j.colsurfb.2020.111287

Mucus-penetrating PEGylated polysuccinimide-based nanocarrier for intravaginal delivery of siRNA battling sexually transmitted infections

Colloids Surf B Biointerfaces. 2020 Dec:196:111287. doi: 10.1016/j.colsurfb.2020.111287. Epub 2020 Jul 29.

Authors

Sarah Currie¹, Seungil Kim², Xiaochen Gu³, Xiaoou Ren⁴, Francis Lin⁵, Shangxi Liu⁶, Chengbo Yang⁶, Ji-Heung Kim⁷, Song Liu⁸

Affiliations

¹ Department of Biosystems Engineering, Faculty of Agricultural and Food Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
² Biomedical Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, Manitoba, Canada; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
³ College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
⁴ Department of Biosystems Engineering, Faculty of Agricultural and Food Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Physics and Astronomy, University of Manitoba, Winnipeg, Manitoba, Canada.
⁵ Department of Biosystems Engineering, Faculty of Agricultural and Food Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Biomedical Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Physics and Astronomy, University of Manitoba, Winnipeg, Manitoba, Canada.
⁶ Department of Animal Science, University of Manitoba, Winnipeg, Manitoba, Canada.
⁷ Polymer Technology Institute, School of Chemical Engineering, Sungkyunkwan University, Gyeonggi, South Korea.
⁸ Department of Biosystems Engineering, Faculty of Agricultural and Food Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Biomedical Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address: song.liu@umanitoba.ca.

PMID: 32768985
DOI: 10.1016/j.colsurfb.2020.111287

Abstract

Intravaginal delivery of siRNA for prevention of sexually transmitted infections faces obstacles such as the acidic environment and vaginal mucus barrier. To achieve effective protection and delivery of siRNA, we developed a polysuccinimide (PSI)-based nanocarrier (PSI-PEG-API-PMA, PPAP) by conjugating methoxy polyethylene glycol amine (Me-PEG-NH₂, Mw 5000), 1-(3-aminopropyl)imidazole (API), and 1-pyrenemethylamine hydrochloride (PMA) to PSI. PPAP demonstrated a spherical self-assembled nanostructure before and after encapsulation of a model siRNA. Variable electrostatic interaction between API and siRNA at acidic vs. neutral pH accomplished significantly lower burst release at pH 4.2 (4 ± 1%) than pH 7.0 (26 ± 5%) within 1 h. PEGylation enabled siRNA-PPAP to achieve higher mucus penetration efficiency (64 ± 17%) than free siRNA (27 ± 5%) for 24 h. Moreover, in vitro study showed minimal toxicity, successful internalization of siRNA-PPAP in HeLa cells and improved gene knockdown (97.5 ± 0.4%). Overall, PPAP is promising for developing preventative treatments for battling sexually transmitted infections.

Keywords: HSV-2 prevention; Intravaginal nanomedicine; Mucus-penetrating siRNA nanocarrier; Polysuccinimide (PSI)-based nanocarrier; Preventing sexually transmitted infections.

MeSH terms

Aspartic Acid / analogs & derivatives
Female
HeLa Cells
Humans
Mucus
Nanoparticles*
Polyethylene Glycols
RNA, Small Interfering / genetics
Sexually Transmitted Diseases*

Substances

RNA, Small Interfering
poly-DL-succinimide
Aspartic Acid
Polyethylene Glycols