Development and Evaluation of a Thermosensitive In Situ Gel Formulation for Intravaginal Delivery of

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Sep 23

PMID 36145685

Authors

Ye Zhao

Tianyuan Wang

Ziyi Chen

Hao Ren

Ping Song

Yingying Zhu

Shan Liang

Chimeng Tzeng

Affiliations

Soon will be listed here.

Abstract

In situ administration of vaginal probiotics has been proposed as an effective prevention strategy against gynecological diseases caused by microecological disorders. In this study, a thermosensitive in situ gel formulation was prepared for intravaginal delivery of . The optimized formulation was characterized for the rheological properties, in vitro release properties, and microencapsulation efficiency. The mixtures of poloxamer 407 (26.0% /) and 188 (9.0% /) produced an increase in gelation extent at 37 °C after dilution in simulated vaginal fluid (SVF). The presence of a low concentration of hyaluronic acid (HA, 0.3% /) improved the mucoadhesive properties and the capability to gel at 37 °C. Additionally, the viability of encapsulated with alginate or via co-extrusion technique with fructooligosaccharide (FOS, 0.5% /) was maintained at 11 log CFU/mL for eight weeks at 4 °C. In conclusion, the evaluation of the in situ thermosensitive gel formulation was shown to be efficacious for intravaginal delivery of with suitable textural and rheological properties.

Citing Articles

Development of synergistic antifungal in situ gel of miconazole nitrate loaded microemulsion as a novel approach to treat vaginal candidiasis.

Alwan O, Jaafar I Sci Rep. 2024; 14(1):23168.

PMID: 39369062 PMC: 11455884. DOI: 10.1038/s41598-024-74021-3.

Numerical Mechanistic Modelling of Drug Release from Solvent-Removal Zein-Based In Situ Gel.

Senarat S, Pornsawad P, Lertsuphotvanit N, Ostergaard J, Phaechamud T Pharmaceutics. 2023; 15(10).

PMID: 37896160 PMC: 10609933. DOI: 10.3390/pharmaceutics15102401.

The Potential of ATCC 14917 in the Development of Alginate-Based Gel Formulations with Anti- Properties.

Sodre M, Ferraz F, Alencar A, Silva K, Silva D, Dos Santos Silva L Pharmaceuticals (Basel). 2023; 16(8).

PMID: 37631027 PMC: 10458396. DOI: 10.3390/ph16081112.

Fabrication and characterization of bioprints with Lactobacillus crispatus for vaginal application.

Kyser A, Masigol M, Mahmoud M, Ryan M, Lewis W, Lewis A J Control Release. 2023; 357:545-560.

PMID: 37076014 PMC: 10696519. DOI: 10.1016/j.jconrel.2023.04.023.

Protective Effects of against High-Cholesterol Diet-Induced Fatty Liver and Regulation of Host Gene Expression Profiles.

He T, Lykov N, Luo X, Wang H, Du Z, Chen Z Int J Mol Sci. 2023; 24(3).

PMID: 36768377 PMC: 9917166. DOI: 10.3390/ijms24032053.

References

Wang X, Liu G, Ma J, Guo S, Gao L, Jia Y . In situ gel-forming system: an attractive alternative for nasal drug delivery. Crit Rev Ther Drug Carrier Syst. 2013; 30(5):411-34. DOI: 10.1615/critrevtherdrugcarriersyst.2013007362. View

Di Costanzo M, Berni Canani R . Lactose Intolerance: Common Misunderstandings. Ann Nutr Metab. 2019; 73 Suppl 4:30-37. DOI: 10.1159/000493669. View

Hajar-Azhari S, Rahim M, Sarbini S, Muhialdin B, Olusegun L, Saari N . Enzymatically synthesised fructooligosaccharides from sugarcane syrup modulate the composition and short-chain fatty acid production of the human intestinal microbiota. Food Res Int. 2021; 149:110677. DOI: 10.1016/j.foodres.2021.110677. View

Taylor B, Darville T, Haggerty C . Does bacterial vaginosis cause pelvic inflammatory disease?. Sex Transm Dis. 2013; 40(2):117-22. DOI: 10.1097/OLQ.0b013e31827c5a5b. View

Thapa R, Gurung S, Parat M, Parekh H, Pandey P . Application of Sol-Gels for Treatment of Gynaecological Conditions-Physiological Perspectives and Emerging Concepts in Intravaginal Drug Delivery. Gels. 2022; 8(2). PMC: 8871440. DOI: 10.3390/gels8020099. View

Chen Y, Lee J, Meng M, Cui N, Dai C, Jia Q . An Overview on Thermosensitive Oral Gel Based on Poloxamer 407. Materials (Basel). 2021; 14(16). PMC: 8399853. DOI: 10.3390/ma14164522. View

Unagolla J, Jayasuriya A . Drug transport mechanisms and in vitro release kinetics of vancomycin encapsulated chitosan-alginate polyelectrolyte microparticles as a controlled drug delivery system. Eur J Pharm Sci. 2017; 114:199-209. PMC: 5805659. DOI: 10.1016/j.ejps.2017.12.012. View

Nappi R, Kotek M, Brestansky A, Giordan N, Beriotto I, Tramentozzi E . Treatment of vulvo-vaginal atrophy with hyaluronate-based gel: a randomized controlled study. Minerva Obstet Gynecol. 2021; 74(6):480-488. DOI: 10.23736/S2724-606X.21.04841-7. View

Selle K, Klaenhammer T . Genomic and phenotypic evidence for probiotic influences of Lactobacillus gasseri on human health. FEMS Microbiol Rev. 2013; 37(6):915-35. DOI: 10.1111/1574-6976.12021. View

10.

Sobel R, Sobel J . Metronidazole for the treatment of vaginal infections. Expert Opin Pharmacother. 2015; 16(7):1109-15. DOI: 10.1517/14656566.2015.1035255. View

11.

Maldonado-Barragan A, Caballero-Guerrero B, Martin V, Ruiz-Barba J, Rodriguez J . Purification and genetic characterization of gassericin E, a novel co-culture inducible bacteriocin from Lactobacillus gasseri EV1461 isolated from the vagina of a healthy woman. BMC Microbiol. 2016; 16:37. PMC: 4788914. DOI: 10.1186/s12866-016-0663-1. View

12.

Oerlemans E, Bellen G, Claes I, Henkens T, Allonsius C, Wittouck S . Impact of a lactobacilli-containing gel on vulvovaginal candidosis and the vaginal microbiome. Sci Rep. 2020; 10(1):7976. PMC: 7224289. DOI: 10.1038/s41598-020-64705-x. View

13.

Owen D, Katz D . A vaginal fluid simulant. Contraception. 1999; 59(2):91-5. DOI: 10.1016/s0010-7824(99)00010-4. View

14.

Kalia N, Singh J, Kaur M . Microbiota in vaginal health and pathogenesis of recurrent vulvovaginal infections: a critical review. Ann Clin Microbiol Antimicrob. 2020; 19(1):5. PMC: 6986042. DOI: 10.1186/s12941-020-0347-4. View

15.

Ur-Rehman T, Tavelin S, Grobner G . Chitosan in situ gelation for improved drug loading and retention in poloxamer 407 gels. Int J Pharm. 2011; 409(1-2):19-29. DOI: 10.1016/j.ijpharm.2011.02.017. View

16.

Silva K, Kawazoe Sato A . Biopolymer gels containing fructooligosaccharides. Food Res Int. 2017; 101:88-95. DOI: 10.1016/j.foodres.2017.08.042. View

17.

Dos Santos A, Carvalho S, Araujo V, Carvalho G, Gremiao M, Chorilli M . Recent advances in hydrogels as strategy for drug delivery intended to vaginal infections. Int J Pharm. 2020; 590:119867. DOI: 10.1016/j.ijpharm.2020.119867. View

18.

Sun L, Tian W, Guo X, Zhang Y, Liu X, Li X . Lactobacillus gasseri JM1 with potential probiotic characteristics alleviates inflammatory response by activating the PI3K/Akt signaling pathway in vitro. J Dairy Sci. 2020; 103(9):7851-7864. DOI: 10.3168/jds.2020-18187. View

19.

Brotman R, Klebanoff M, Nansel T, Yu K, Andrews W, Zhang J . Bacterial vaginosis assessed by gram stain and diminished colonization resistance to incident gonococcal, chlamydial, and trichomonal genital infection. J Infect Dis. 2010; 202(12):1907-15. PMC: 3053135. DOI: 10.1086/657320. View

20.

Ricci A, Allende A, Bolton D, Chemaly M, Davies R, Girones R . Update of the list of QPS-recommended biological agents intentionally added to food or feed as notified to EFSA 6: suitability of taxonomic units notified to EFSA until March 2017. EFSA J. 2020; 15(7):e04884. PMC: 7009974. DOI: 10.2903/j.efsa.2017.4884. View