A Thermosensitive Gel Based on W1/o/w2 Multiple Microemulsions for the Vaginal Delivery of Small Nucleic Acid

Overview

Journal Drug Deliv

Specialty Pharmacology

Date 2019 Mar 2

PMID 30822166

Citations 9

Authors

Jiu Wang

Yajing Wang

Ziqiang Wang

Fan Wang

Jie He

Xiaoyun Yang

Weidong Xie

Ying Liu

Yaou Zhang

Affiliations

Soon will be listed here.

Abstract

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 ddHO, 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.

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References

Woolfson A, Malcolm R, Gallagher R . Drug delivery by the intravaginal route. Crit Rev Ther Drug Carrier Syst. 2000; 17(5):509-55. View

DCruz O, Uckun F . Gel-microemulsions as vaginal spermicides and intravaginal drug delivery vehicles. Contraception. 2001; 64(2):113-23. DOI: 10.1016/s0010-7824(01)00233-5. View

Sadurni N, Solans C, Azemar N, Garcia-Celma M . Studies on the formation of O/W nano-emulsions, by low-energy emulsification methods, suitable for pharmaceutical applications. Eur J Pharm Sci. 2005; 26(5):438-45. DOI: 10.1016/j.ejps.2005.08.001. View

Palliser D, Chowdhury D, Wang Q, Lee S, Bronson R, Knipe D . An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. Nature. 2005; 439(7072):89-94. DOI: 10.1038/nature04263. View

Worle-Knirsch J, Pulskamp K, Krug H . Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Lett. 2006; 6(6):1261-8. DOI: 10.1021/nl060177c. View

Wu Y, Navarro F, Lal A, Basar E, Pandey R, Manoharan M . Durable protection from Herpes Simplex Virus-2 transmission following intravaginal application of siRNAs targeting both a viral and host gene. Cell Host Microbe. 2009; 5(1):84-94. PMC: 2654264. DOI: 10.1016/j.chom.2008.12.003. View

Woodrow K, Cu Y, Booth C, Saucier-Sawyer J, Wood M, Saltzman W . Intravaginal gene silencing using biodegradable polymer nanoparticles densely loaded with small-interfering RNA. Nat Mater. 2009; 8(6):526-33. PMC: 2693358. DOI: 10.1038/nmat2444. View

Andrews G, Donnelly L, Jones D, Curran R, Morrow R, Woolfson A . Characterization of the rheological, mucoadhesive, and drug release properties of highly structured gel platforms for intravaginal drug delivery. Biomacromolecules. 2009; 10(9):2427-35. PMC: 2745825. DOI: 10.1021/bm9003332. View

Baloglu E, Ay Senyigit Z, Karavana S, Bernkop-Schnurch A . Strategies to prolong the intravaginal residence time of drug delivery systems. J Pharm Pharm Sci. 2010; 12(3):312-36. DOI: 10.18433/j3hp41. View

10.

Schafer J, Hobel S, Bakowsky U, Aigner A . Liposome-polyethylenimine complexes for enhanced DNA and siRNA delivery. Biomaterials. 2010; 31(26):6892-900. DOI: 10.1016/j.biomaterials.2010.05.043. View

11.

Wu S, Chang H, Burgess M, McMillan N . Vaginal delivery of siRNA using a novel PEGylated lipoplex-entrapped alginate scaffold system. J Control Release. 2011; 155(3):418-26. DOI: 10.1016/j.jconrel.2011.02.002. View

12.

Geusens B, Strobbe T, Bracke S, Dynoodt P, Sanders N, Van Gele M . Lipid-mediated gene delivery to the skin. Eur J Pharm Sci. 2011; 43(4):199-211. DOI: 10.1016/j.ejps.2011.04.003. View

13.

Li N, Yu M, Deng L, Yang J, Dong A . Thermosensitive hydrogel of hydrophobically-modified methylcellulose for intravaginal drug delivery. J Mater Sci Mater Med. 2012; 23(8):1913-9. DOI: 10.1007/s10856-012-4664-9. View

14.

Kammona O, Kiparissides C . Recent advances in nanocarrier-based mucosal delivery of biomolecules. J Control Release. 2012; 161(3):781-94. DOI: 10.1016/j.jconrel.2012.05.040. View

15.

Zheng M, Pavan G, Neeb M, Schaper A, Danani A, Klebe G . Targeting the blind spot of polycationic nanocarrier-based siRNA delivery. ACS Nano. 2012; 6(11):9447-54. PMC: 3882193. DOI: 10.1021/nn301966r. View

16.

Ho E, Osooly M, Strutt D, Masin D, Yang Y, Yan H . Characterization of long-circulating cationic nanoparticle formulations consisting of a two-stage PEGylation step for the delivery of siRNA in a breast cancer tumor model. J Pharm Sci. 2012; 102(1):227-36. DOI: 10.1002/jps.23351. View

17.

Mishra S, Vaughn A, Devore D, Roth C . Delivery of siRNA silencing Runx2 using a multifunctional polymer-lipid nanoparticle inhibits osteogenesis in a cell culture model of heterotopic ossification. Integr Biol (Camb). 2012; 4(12):1498-507. PMC: 4534437. DOI: 10.1039/c2ib20200j. View

18.

Yang S, Chen Y, Ahmadie R, Ho E . Advancements in the field of intravaginal siRNA delivery. J Control Release. 2013; 167(1):29-39. DOI: 10.1016/j.jconrel.2012.12.023. View

19.

Vicentini F, Borgheti-Cardoso L, Depieri L, de Macedo Mano D, Fedatto Abelha T, Petrilli R . Delivery systems and local administration routes for therapeutic siRNA. Pharm Res. 2013; 30(4):915-31. PMC: 7088712. DOI: 10.1007/s11095-013-0971-1. View

20.

Vanic Z, Skalko-Basnet N . Nanopharmaceuticals for improved topical vaginal therapy: can they deliver?. Eur J Pharm Sci. 2013; 50(1):29-41. DOI: 10.1016/j.ejps.2013.04.035. View