Applied Sciences-Basel
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2019
·Vol. 9
·期 8
·1638
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IF 2.217
Lei Nie,Peng Zou,Jing Dong,Meng Sun,Peng Ding,Yanting Han,Chingching Ji,Qiuju Zhou,Hongyu Yuan,Jinping Suo
Injectable intravaginal hydrogels could deliver drugs systemically without hepatic first pass effect. This paper focuses on the contraceptive function of an injectable temperature-sensitive four-arm star-shaped poly(D,L-lactic-co-glycolic acid)-b-methoxy poly(ethylene glycol) (4sPLGA-mPEG) block copolymer hydrogels as a carrier of three drugs. In vitro controlled release profiles were investigated via HPLC, and it showed that the cumulative release amounts of indomethacin (IMC), gestodene (GSD), and ethinyl estradiol (EE) from copolymer hydrogels could be regulated by adjusting the lactide/glycolide (LA/GA) mol ratio. In addition, in vitro release profiles of IMC, GSD, and EE well corresponded to Higuchi model. The acute toxicity of copolymer hydrogels loaded with different dosage contents multi-drug was evaluated in vivo. As to the high dosage group, the uterus was hydropic at day 1 and ulcerated at day 5, followed with intestinal adhesion. Regarding the middle dosage group, no festering of tissues was observed and, blood coagulum existed in the uterus at different days. For low dosage group, no significant tissue necrosis was found. Finally, the antifertility experiments confirmed that hydrogels loaded with the multi-drug had an excellent contraceptive effect. The above results indicated that injectable copolymer hydrogel as a multi-drug carrier was promising as a novel contraception method.Keywords:vaginal hydrogels;injectable;contraception;multi-drug release;mucoadhesive;biodegradability
研究领域:
药学
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生殖健康
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聚合物化学
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药物递送系统
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2025
·
IF 4.3
Xuena Zhang,Fengqiang Zhang,Chongwei Yin,Juan Xu,Ting Wang
Ethinylestradiol (EE) is a clinically used estrogen with antifertility effects that is poorly water soluble, limiting bioavailability and preventing long-term release when administered orally. This study addresses these challenges through the development of a novel injectable thermosensitive hydrogel that both improves hydrophobic EE dispersion and enables sustained in vivo release, presenting significant potential for long-term contraception. Carboxymethyl-β-cyclodextrin (CM-β-CD) was synthesized to encapsulate EE, thereby enhancing its solubility and distribution in the hydrogel matrix. We found that hydrogels prepared by adding 0.5% (w/v) oxidized dextran (ODex) to the chitosan/sodium β-glycerophosphate (CS/ODex/β-GP) system exhibited mechanical strength favorable for cell growth compared to conventional CS/β-GP, resolved the problems of poor stability and mechanical strength of CS/β-GP hydrogels, and ensured effective retention and delivery in vivo . A 240h drug release study demonstrated the hydrogel’s ability to sustain release, highlighting its potential to prolong contraceptive efficacy. Biocompatibility testing showed cell viability in excess of 85%. FTIR and SEM characterization further confirmed the functional structure and morphology of the hydrogel. This thermosensitive injection system provides a promising platform for the long-term release of hydrophobic drugs such as EE, providing an innovative approach to extended contraceptive delivery.
研究领域:
药剂学
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生物材料
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生殖医学
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药物递送系统
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高分子药物载体
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转化医学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2023
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IF 17.1
Zhenning Su,Cancan Yao,Joanne Tipper,Lijun Yang,Xiangbo Xu,Xihua Chen,Guo Bao,Bin He,Xiaoxue Xu,Yufeng Zheng
Effective contraceptives have been comprehensively adopted by women to prevent the negative consequences of unintended pregnancy for women, families, and societies. With great contributions of traditional hormonal drugs and intrauterine devices (IUDs) to effective female contraception by inhibiting ovulation and deactivating sperm, their long-standing side effects on hormonal homeostasis and reproductive organs for females remain concerns. Herein, we proposed a nanostrategy for female contraceptives, inducing embryonic trophoblast cell death using nanoparticles to prevent embryo implantation. Cupric oxide nanoparticles (CuO NPs) were adopted in this work to verify the feasibility of the nanostrategy and its contraceptive efficacy. We carried out the in vitro assessment on the interaction of CuO NPs with trophoblast cells using the HTR8/SVneo cell line. The results showed that the CuO NPs were able to be preferably uptaken into cells and induced cell damage via a variety of pathways including oxidative stress, mitochondrial damage, DNA damage, and cell cycle arrest to induce cell death of apoptosis, ferroptosis, and cuproptosis. Moreover, the key regulatory processes and the key genes for cell damage and cell death caused by CuO NPs were revealed by RNA-Seq. We also conducted in vivo experiments using a rat model to examine the contraceptive efficacy of both the bare CuO NPs and the CuO/thermosensitive hydrogel nanocomposite. The results demonstrated that the CuO NPs were highly effective for contraception. There was no sign of disrupting the homeostasis of copper and hormone, or causing inflammation and organ damage in vivo. In all, this nanostrategy exhibited huge potential for contraceptive development with high biosafety, efficacy, clinical translation, nonhormonal style, and on-demand for women.
研究领域:
纳米技术
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生殖生物学
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避孕科学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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