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A Cocktail-Inspired Male Birth Control Strategy with Physical/Chemical Dual Contraceptive Effects and Remote SelfCleared Properties Weiwei Bao,†,§,# Lin Xie,†,∥,# Xuhui Zeng,⊥ Hang Kang,⊥ Shiqi Wen,⊥ Ben Cui,† Wenting Li,† Yisong Qian,† Jie Wu,† Ting Li,† Keyu Deng,† Hong-Bo Xin,† and Xiaolei Wang*,†,‡ †
The National Engineering Research Center for Bioengineering Drugs and the Technologies: Institition of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330088, P.R. China ‡ College of Chemistry, Nanchang University, Nanchang, Jiangxi 330088, P.R. China § College of Basic Medicine, Nanchang University, Nanchang, Jiangxi 330088, P.R. China ∥ College of Life Science, Nanchang University, Nanchang, Jiangxi 330088, P.R. China ⊥ Institute of Life Science, Nanchang University, Nanchang, Jiangxi 330088, P.R. China S Supporting Information *
ABSTRACT: Inspired by cocktails, we designed a medium term (2−20 weeks) male contraceptive strategy. Through a sequential injection process of four reagents (calcium alginate hydrogel, PEG-Au nanoparticles (PEGAuNps), EDTA, and PEG-AuNps), physical clogging of the vas deferens and chemical inhibition of the sperm motility were realized simultaneously. The contraceptive period could be directly preset by adjusting the injection ratio of each reagent. More interesting, the embolism area could be readily dredged through a short-time noninvasive near-infrared irradiation. The present study offered an effective and reversible manner to fill the gap of current medium-term contraceptive strategy. In addition, the proposed in vivo pipeline plugging technology, with a flexible noninvasive self-cleared characteristic, might also provide a convenient and reliable strategy for some other biomedical engineering researches. KEYWORDS: near-infrared irradiation, alginate hydrogel, controlled release, AuNps, noninvasive fertility restoration
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Currently, the research directions of reversible male contraception method can be roughly divided into two categories. (1) Drug methods: Though most have good reversibility and effectiveness, such as RAR,6 JQ1,7 GnRH,8 etc., they still retain some inherent limitations such as expense, side effects, and durability length. (2) Surgery methods: For instance, Indian scientists have developed a sperm-blocking agent called RUSUG that shows a good azoospermia effect in rabbit experiments for 30−60 days. After flushing out with DMSO or sodium bicarbonate, the contraceptive effect could be reversed.9 However, the relative reversion process requires a second open surgery. On the other hand, Wang et al. injected methoxypoly(ethylene glycol)-modified AuNps into the testis of male rats in situ. By heating under near-infrared light
ontraception has always been an important but underestimated research subject. An estimated 85 million unintended pregnancies occur annually worldwide, with half ending in abortion and 13% in miscarriage.1 For decades, women have shouldered the main burden of contraception, but long-term use of contraceptives could give rise to several side effects, such as venous thromboembolism2 and abnormal endometrial angiogenesis.3 In the field of male contraception, apart from condoms and vasectomy, there is almost no appropriate alternative choice supplied for men.4 Although condoms can prevent sexually transmitted diseases, they also affect the quality of sexual life and have a high failure rate (∼19%). On the other hand, vasectomy is very effective (99%) but suffers from limited reversibility (