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Composite thermoresponsive hydrogel with auranofin-loaded nanoparticles for topical treatment of vaginal trichomonad infection.
Adv Ther (Weinh). 2019 Dec; 2(12)AT

Abstract

Trichomonas vaginalis is responsible for the most common non-viral sexually-transmitted disease worldwide. Standard treatment is with oral nitro-heterocyclic compounds, metronidazole or tinidazole, but resistance to these drugs is emerging and adverse effects can be problematic. Topical treatment offers potential benefits for increasing local drug concentrations and efficacy, while reducing systemic drug exposure, but no topical strategies are currently approved for trichomoniasis. The anti-rheumatic drug, auranofin (AF), was recently discovered to have significant trichomonacidal activity, but has a long plasma half-life and significant adverse effects. Here, we used this drug as a model to develop a novel topical formulation composed of AF-loaded nanoparticles (NP) embedded in a thermoresponsive hydrogel for intravaginal administration. The AF-NP composite gel showed sustained drug release for at least 12 h, and underwent sol-gel transition with increased viscoelasticity within a minute. Intravaginal administration in mice showed excellent NP retention for >6 h and markedly increased local AF levels, but reduced plasma and liver levels compared to oral treatment with a much higher dose. Furthermore, intravaginal AF-NP gel greatly outperformed oral AF in eliminating vaginal trichomonad infection in mice, while causing no systemic or local toxicity. These results show the potential of the AF-NP hydrogel formulation for effective topical therapy of vaginal infections.

Authors+Show Affiliations

Department of NanoEngineering and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA.Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.Department of NanoEngineering and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA.Department of NanoEngineering and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA.Department of NanoEngineering and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA.Department of NanoEngineering and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA.Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32377561

Citation

Zhang, Yue, et al. "Composite Thermoresponsive Hydrogel With Auranofin-loaded Nanoparticles for Topical Treatment of Vaginal Trichomonad Infection." Advanced Therapeutics, vol. 2, no. 12, 2019.
Zhang Y, Miyamoto Y, Ihara S, et al. Composite thermoresponsive hydrogel with auranofin-loaded nanoparticles for topical treatment of vaginal trichomonad infection. Adv Ther (Weinh). 2019;2(12).
Zhang, Y., Miyamoto, Y., Ihara, S., Yang, J. Z., Zuill, D. E., Angsantikul, P., Zhang, Q., Gao, W., Zhang, L., & Eckmann, L. (2019). Composite thermoresponsive hydrogel with auranofin-loaded nanoparticles for topical treatment of vaginal trichomonad infection. Advanced Therapeutics, 2(12). https://doi.org/10.1002/adtp.201900157
Zhang Y, et al. Composite Thermoresponsive Hydrogel With Auranofin-loaded Nanoparticles for Topical Treatment of Vaginal Trichomonad Infection. Adv Ther (Weinh). 2019;2(12) PubMed PMID: 32377561.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Composite thermoresponsive hydrogel with auranofin-loaded nanoparticles for topical treatment of vaginal trichomonad infection. AU - Zhang,Yue, AU - Miyamoto,Yukiko, AU - Ihara,Sozaburo, AU - Yang,Justin Z, AU - Zuill,Douglas E, AU - Angsantikul,Pavimol, AU - Zhang,Qiangzhe, AU - Gao,Weiwei, AU - Zhang,Liangfang, AU - Eckmann,Lars, Y1 - 2019/10/30/ PY - 2020/12/01/pmc-release PY - 2020/5/8/entrez PY - 2020/5/8/pubmed PY - 2020/5/8/medline KW - Trichomoniasis KW - antimicrobial KW - drug delivery KW - hydrogel KW - nanoparticle JF - Advanced therapeutics JO - Adv Ther (Weinh) VL - 2 IS - 12 N2 - Trichomonas vaginalis is responsible for the most common non-viral sexually-transmitted disease worldwide. Standard treatment is with oral nitro-heterocyclic compounds, metronidazole or tinidazole, but resistance to these drugs is emerging and adverse effects can be problematic. Topical treatment offers potential benefits for increasing local drug concentrations and efficacy, while reducing systemic drug exposure, but no topical strategies are currently approved for trichomoniasis. The anti-rheumatic drug, auranofin (AF), was recently discovered to have significant trichomonacidal activity, but has a long plasma half-life and significant adverse effects. Here, we used this drug as a model to develop a novel topical formulation composed of AF-loaded nanoparticles (NP) embedded in a thermoresponsive hydrogel for intravaginal administration. The AF-NP composite gel showed sustained drug release for at least 12 h, and underwent sol-gel transition with increased viscoelasticity within a minute. Intravaginal administration in mice showed excellent NP retention for >6 h and markedly increased local AF levels, but reduced plasma and liver levels compared to oral treatment with a much higher dose. Furthermore, intravaginal AF-NP gel greatly outperformed oral AF in eliminating vaginal trichomonad infection in mice, while causing no systemic or local toxicity. These results show the potential of the AF-NP hydrogel formulation for effective topical therapy of vaginal infections. SN - 2366-3987 UR - https://www.unboundmedicine.com/medline/citation/32377561/Composite_thermoresponsive_hydrogel_with_auranofin-loaded_nanoparticles_for_topical_treatment_of_vaginal_trichomonad_infection L2 - https://antibodies.cancer.gov/detail/CPTC-PSMD4-1 DB - PRIME DP - Unbound Medicine ER -
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