“皮下注射接种”终结者：疫苗帖片——免疫保护能力更强

Vaccine-Delivery Patch With Dissolving Microneedles Eliminates 'Sharps,' Boosts Protection
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4 R: h/ ~! \5 K7 mScienceDaily (July 19, 2010) — A new vaccine-delivery patch based on hundreds of microscopic needles that dissolve into the skin could allow persons without medical training to painlessly administer vaccines -- while providing improved immunization against diseases such as influenza.

An array of 36 dissolving microneedles is shown here on a fingertip for size comparison. (Credit: Jeong-Woo Lee)

7 Q) d: `) s  FPatches containing micron-scale needles that carry vaccine with them as they dissolve into the skin could simplify immunization programs by eliminating the use of hypodermic needles -- and their "sharps" disposal and re-use concerns. Applied easily to the skin, the microneedle patches could allow self-administration of vaccine during pandemics and simplify large-scale immunization programs in developing nations.
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Details of the dissolving microneedle patches and immunization benefits observed in experimental mice were reported July 18th in the advance online publication of the journal Nature Medicine. Conducted by researchers from Emory University and the Georgia Institute of Technology, the study is believed to be the first to evaluate the immunization benefits of dissolving microneedles. The research was supported by the National Institutes of Health (NIH).

1 x' k$ u, `6 a. Y6 r/ K7 m( o"In this study, we have shown that a dissolving microneedle patch can vaccinate against influenza at least as well, and probably better than, a traditional hypodermic needle," said Mark Prausnitz, a professor in the Georgia Tech School of Chemical and Biomolecular Engineering.
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# `- a9 t6 E; Q+ y) ^# ]Just 650 microns in length and assembled into an array of 100 needles for the mouse study, the dissolving microneedles penetrate the outer layers of skin. Beyond their other advantages, the dissolving microneedles appear to provide improved immunity to influenza when compared to vaccination with hypodermic needles.

"The skin is a particularly attractive site for immunization because it contains an abundance of the types of cells that are important in generating immune responses to vaccines," said Richard Compans, professor of microbiology and immunology at Emory University School of Medicine.
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6 g! b& H4 C+ LIn the study, one group of mice received the influenza vaccine using traditional hypodermic needles injecting into muscle; another group received the vaccine through dissolving microneedles applied to the skin, while a control group had microneedle patches containing no vaccine applied to their skin. When infected with influenza virus 30 days later, both groups that had received the vaccine remained healthy while mice in the control group contracted the disease and died.

) ^# S! X- h/ d3 Y8 yThree months after vaccination, the researchers also exposed a different group of immunized mice to flu virus and found that animals vaccinated with microneedles appeared to have a better "recall" response to the virus and thus were able to clear the virus from their lungs more effectively than those that received vaccine with hypodermic needles.

"Another advantage of these microneedles is that the vaccine is present as a dry formulation, which will enhance its stability during distribution and storage," said Ioanna Skountzou, an Emory University assistant professor.

, a) W) f3 \7 O$ ^, h% R. K1 P  }Pressed into the skin, the microneedles quickly dissolve in bodily fluids, leaving only the water-soluble backing. The backing can be discarded because it no longer contains any sharps.
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"We envision people getting the patch in the mail or at a pharmacy and then self administering it at home," said Sean Sullivan, the study's lead author from Georgia Tech. "Because the microneedles on the patch dissolve away into the skin, there would be no dangerous sharp needles left over."
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- ?  L# a0 J2 _% {( c" H9 x( \The microneedle arrays were made from a polymer material, poly-vinyl pyrrolidone, that has been shown to be safe for use in the body. Freeze-dried vaccine was mixed with the vinyl-pyrrolidone monomer before being placed into microneedle molds and polymerized at room temperature using ultraviolet light.
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/ P% T3 H$ v( y4 h& Q1 qIn many parts of the world, poor medical infrastructure leads to the re-use of hypodermic needles, contributing to the spread of diseases such as HIV and hepatitis B. Dissolving microneedle patches would eliminate re-use while allowing vaccination to be done by personnel with minimal training.

" i! g) r" f% D, mThough the study examined only the administration of flu vaccine with the dissolving microneedles, the technique should be useful for other immunizations. If mass-produced, the microneedle patches are expected to cost about the same as conventional needle-and-syringe techniques, and may lower the overall cost of immunization programs by reducing personnel costs and waste disposal requirements, Prausnitz said.
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Before dissolving microneedles can be made widely available, however, clinical studies will have to be done to assure safety and effectiveness. Other vaccine formulation techniques may also be studied, and researchers will want to better understand why vaccine delivery with dissolving microneedles has been shown to provide better protection.

Beyond those already mentioned, the study involved Jeong-Woo Lee, Vladimir Zarnitsyn, Seong-O Choi and Niren Murthy from Georgia Tech, and Dimitrios Koutsonanos and Maria del Pilar Martin from Emory University.
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' J6 _8 `, P4 a* G, o8 z! F"The dissolving microneedle patch could open up many new doors for immunization programs by eliminating the need for trained personnel to carry out the vaccination," Prausnitz said.

"This approach could make a significant impact because it could enable self-administration as well as simplify vaccination programs in schools and assisted living facilities."
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“皮下注射接种”终结者：疫苗帖片——免疫保护能力更强

《每日科学》2010年7月19日报道 ——一种含有可溶入皮肤的几百个微小针头的新的疫苗帖片，无须医疗培训即可进行疫苗接种 —— 并且，针对诸如流感的免疫也因此得到了改善。
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* I' h9 W& f- \7 h" \- v" A& w[img][/img]
" O8 N# d. z* b2 S帖片上的所有针头都只有微米刻度大小，针头内含有疫苗并可溶入皮肤；该帖片可完全取代皮下注射针头从而简化了免疫接种过程，同时也回避了后者的针头处置与重新使用问题。微针贴片帖上皮肤十分容易，允许在流感期间个人自我完成“注射”过程，大大简化了发展中国家大规模的免疫接种计划。

有关可降解微针帖片的详情以及小鼠实验中所观察到的帖片免疫接种的优势已于7月18日发表于Nature Medicine.（《自然医学杂志》）在线预览版。来自艾默里大学与乔治亚技术学院的研究者进行了这项研究。本研究已获认同：为医学界首次对可降解微针头免疫优势所进行的评估。本研究得到了国家卫生研究院（NIIH）的支持。
“在本研究中，我们显示：可降解微针帖片至少能够对流感进行接种，并可能比传统的皮下注射针头接种有着更好的效果。” 乔治亚技术学院化学与生物分子工程分院教授马克•普罗斯尼茨（Mark Prausnitz,）说。
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在小鼠实验中，帖片长度只有650微米，上面排列了100个针头；可降解的微针头穿透皮肤的外层。除了其它方面的优势外，可降解微针头较皮下注射针头而言，前者针对流感的免疫保护看起来更强。

! G- Q3 b3 S8 ~, P: p“皮肤对免疫来说是个特别有吸引力的地方，因为皮肤包含了类型极为丰富的细胞，这对疫苗引发的免疫响应特别重要。” 埃默里大学医学院微生物学与免疫学教授里查德•康篷斯（Richard Compans）说。
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在本研究中，一组小鼠以传统的皮下注射方式（针头插入皮下肌肉内注射）接受了流感疫苗，另一组则通过帖在皮肤上的可降解微针头接受疫苗，对照组虽然也接受微针头帖片，但帖片里没有疫苗。30天以后以流感病毒感染小鼠，接受了疫苗的前两组小鼠保持了健康状态，而对照组的小鼠则被感染并最终死亡。
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接种后3个月，研究者又让接受了免疫接种的另一不同研究组的小鼠接触鸟流感病毒，发现用微针帖片接种的动物看来对病毒有更好的“回忆”响应：比起皮下注射接种的小鼠来，帖片接种的小鼠能够将病毒更有效地从其肺部清除出去。

. R8 V9 i+ @: D# ]2 _- k+ G“这些微针的另一个优势是疫苗以干燥形态出现， 这样就加强了疫苗的稳定性，便于运输、分配与储存。”埃默里大学助理教授Ioanna Skountzou说。

帖片紧帖皮肤后，微针就会在体液中快速溶解，留下的只是可溶于水的衬垫物。衬垫因为不包含任何尖利物，可以丢弃。

“我们想象，人们可以从邮件或药店（药房）里取到帖片，然后在家里给自己接种。因为帖片上的微针会溶入皮肤，不会有锋利的针头留下来。” 本研究的第一作者、来自乔治亚技术学院的Sean Sullivan说。

" g& R( B& G  ^" C微针系列用聚合材料聚醋酸乙烯吡咯烷酮制造，已有证据显示本研究中使用该材料是安全的。而冷冻干燥的疫苗则在置入微针模子前与乙烯基吡咯烷酮单体混合、并在室温下用紫外光将混合物聚合。
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( X' y) |9 N0 _0 ]# ?2 |在世界上的许多地方，医疗基础设施落后所导致的皮下注射针头的反复使用是HIV与乙肝传播的途径之一。可降解微针帖片将终结皮下注射接种的历史，相关人员几乎不需要任何培训就可以完成接种任务。

普罗斯尼茨说，虽然本研究只检查了鸟流感疫苗的微针帖片接种情况，该技术对于其它免疫工作也非常有用。如果大量生产的话，微针帖片有希望达到与传统“针头¬--注射器”技术一样的成本，并且可通过减少人力成本与医疗废物处理成本来降低免疫计划的总体成本。
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不过，在可降解微针帖片大量投入使用之前，应该有临床试验研究来确保其安全性与有效性。其它疫苗形式的相关技术也应该得到研究，并且，研究者也要更好地理解为何可降解微针帖片能够提供更好的保护。
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# S0 x$ E: P6 W# `) P  p+ i除了以上提到的人外，来自乔治亚技术学院的Jeong-Woo Lee、Vladimir Zarnitsyn、Seong-O Choi 与 Niren Murthy，以及来自埃默里大学的Dimitrios Koutsonanos 与 Maria del Pilar Martin也参加了本研究。

0 ~! F3 [- b  L9 g普罗斯尼茨说：“可降解微针帖片可能因为不需要对接种人员进行培训而为免疫计划打开了许多新的大门。”

* F+ d/ L0 Q* c) c0 l- }& M3 g“这一方法会产生重大的影响，因为它使自我接种成为可能，也简化了学校与生活协助单位的接种计划。”


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真有这么好的东西