A thermosensitive gel based on w1/o/w2 multiple microemulsions for the vaginal delivery of small nucleic acid

Drug Delivery

Yajing Wang¹  Fan Wang²  Ziqiang Wang²  Xiaoyun Yang²  Jie He²  Weidong Xie²  Yaou Zhang²  Ying Liu³  Jiu Wang⁴ 

[1] Department of Pharmacy, School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, Jiangsu, China;Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China;Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China;School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, Chin;School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei, China;Division of Life Science, Key Lab in Healthy Science and Technology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China;

关键词: Small interfering RNA (siRNA);    multiple microemulsions (MMEs);    low energy emulsification (LEE);    thermosensitive gel;    vaginal delivery;   

DOI  :  10.1080/10717544.2019.1568622

来源: publisher

【 摘 要 】

The present study aims at designing a thermosensitive gel prepared from w1/o/w2 multiple microemulsions (MMEs) for the vaginal delivery of siRNA. The w1/o/w2 MMEs were prepared by two-step emulsifications: the first step was to prepare primary emulsions (w1/o) by low energy emulsification (LEE); the second step was to obtain stable w1/o/w2 MMEs by self-emulsifying. An extensive formulation optimization process was undertaken. The final w1/o/w2 MMEs could be formed in ddH2O, phosphate buffer solution (PBS, pH 7.4) and 1640 culture media with diameter size about 166.5 ± 13.1, 271.0 ± 11.1 and 278.7 ± 12.1 nm respectively. The release rates of siRNA from solutions, MMEs and MMEs-gels were completed within 2 h, 6 h and13 h respectively. The transfection efficiency of MMEs was confirmed both in vitro and in vivo. The relative target gene expressions of MMEs were 0.07 ± 0.05% vs. 0.37 ± 0.06% in Hela cells against Lipofectamine2000® and 1.88% ± 0.00% vs. 9.65% ± 0.02% in mouse vaginal mucosa against PEI. Good biocompatibility of MMEs was verified by cytotoxicity and pathological studies. Overall, our results indicated the potential of the MMEs-gel system for the vaginal delivery of siRNA.

【 授权许可】

CC BY