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Low intensity ultrasound-mediated drug-loaded nanoparticles intravaginal drug delivery: an effective synergistic therapy scheme for treatment of vulvovaginal candidiasis

التفاصيل البيبلوغرافية
العنوان: Low intensity ultrasound-mediated drug-loaded nanoparticles intravaginal drug delivery: an effective synergistic therapy scheme for treatment of vulvovaginal candidiasis
المؤلفون: Min Yang, Yuchao Cao, Zhifei Zhang, Jiajun Guo, Can Hu, Zhibiao Wang, Yonghong Du
المصدر: Journal of Nanobiotechnology, Vol 21, Iss 1, Pp 1-20 (2023)
بيانات النشر: BMC, 2023.
سنة النشر: 2023
المجموعة: LCC:Biotechnology
LCC:Medical technology
مصطلحات موضوعية: Vulvovaginal candidiasis, Low intensity ultrasound, Amphotericin B-loaded PLGA-PEG nanoparticles, Intravaginal drug delivery, Synergistic therapy, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5
الوصف: Abstract Purpose Vulvovaginal candidiasis (VVC) is a mucosal infection of the female lower genital tract for which treatment using conventional antifungal drugs shows limited effectiveness. Herein, amphotericin B-loaded poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (AmB-NPs) were fabricated and combined with low intensity ultrasound (US) to mediate AmB-NPs intravaginal drug delivery to achieve productive synergistic antifungal activity in a rabbit model of VVC. Methods Polymeric AmB-NPs were fabricated by a double emulsion method and the physical characteristics and biosafety of nanoparticles were analyzed. The distribution and tissue permeability of nanoparticles after intravaginal ultrasound irradiation (1.0 MHz, 1.0 W/cm2, 5 min, 50% duty ratio) were observed in the vagina. The synergistic therapeutic activity of US-mediated AmB-NPs treatment was evaluated using an experimental rabbit model of VVC. Vaginal C. albicans colony counts, the pathological structure of the vagina epithelium, and Th1/Th2/Th17-type cytokine and oxidative stress levels were analyzed to investigate the therapeutic effect in vivo. Results The prepared AmB-NPs showed an obvious shell and core structure with uniform size and good dispersion and displayed high biosafety and US-sensitive slow drug release. Ultrasound significantly enhanced nanoparticle transport through the mucus and promoted permeability in the vaginal tissue. US-mediated AmB-NPs treatment effectively increased drug sensitivity, even in the presence of the vaginal mucus barrier in vitro. On the seventh day after treatment in vivo, the combination treatment of AmB-NPs and US significantly reduced the fungal load in the vagina, achieving over 95% clearance rates, and also improved the pathological epithelium structural damage and glycogen secretion function. The expression of Th1 (IFN-γ, IL-2) and Th17 (IL-17) cytokines were significantly increased and Th2 (IL-6, IL-10) cytokines significantly decreased in the US + AmB-NP group. Furthermore, US-mediated AmB-NPs treatment effectively increased C. albicans intracellular reactive oxygen species (ROS) levels and promoted vaginal oxidation and antioxidants to normal levels. Conclusion US-mediated drug-loaded nanoparticles with intravaginal drug delivery exhibited a productive synergistic antifungal effect, which may provide a new non-invasive, safe, and effective therapy for acute or recurrent fungal vaginitis. Graphical Abstract
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1477-3155
Relation: https://doaj.org/toc/1477-3155
DOI: 10.1186/s12951-023-01800-x
URL الوصول: https://doaj.org/article/be27ef8fea874ca28720454bb1d093c3
رقم الأكسشن: edsdoj.be27ef8fea874ca28720454bb1d093c3
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14773155
DOI:10.1186/s12951-023-01800-x