Needleless administration of advanced therapies into the skin via the appendages using a hypobaric patch.
Needleless administration of advanced therapies into the skin via the appendages using a hypobaric patch.
复制标题
使用低压贴片通过附属物无针给药进入皮肤。
DOI：
10.1073/pnas.2120340119
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发表时间：
2022-05-03
影响因子：
11.1
通讯作者：
Jones, Stuart A.
中科院分区：
文献类型：
--
作者：
Benaouda, Faiza;Inacio, Ricardo;Lim, Chui Hua;Park, Haeeun;Pitcher, Thomas;Alhnan, Mohamed A.;Aly, Mazen M. S.;Al-Jamal, Khuloud;Chan, Ka-lung;Gala, Rikhav P.;Sebastia-Saez, Daniel;Cui, Liang;Chen, Tao;Keeble, Julie;Jones, Stuart A.
无针递送到皮肤中将克服有效临床利用诸如纳米材料和大分子的先进疗法的主要障碍。该研究表明，使用包括低压室的贴片来打开皮肤附属物的受控皮肤拉伸（在猪、大鼠和小鼠模型中）可以增加组织的渗透性，并提供一种能够将高级治疗直接递送到皮肤中而不使用针或注射系统的手段。该技术可以促进包括疫苗、RNA和抗原在内的治疗剂的自我施用，从而改善这些产品转化为有效临床用途。先进的治疗通常通过注射进行，即使它们在皮肤组织内起作用，这也增加了脱靶效应的机会。在这里，我们报告了使用的皮肤贴片含有一个低压室，诱导皮肤圆顶的形成，使先进的治疗无针输送直接进入猪，大鼠和小鼠的皮肤。有限元法建模显示，补片中的低压舱使皮肤附件打开32%，使皮肤变薄，并压缩附件壁上皮细胞。这些变化允许直接将H1N1疫苗抗原和双氯芬酸纳米粒递送到皮肤中。皮肤的荧光成像和红外成像显示通过附件无针递送。与肌肉注射相比，贴片在小鼠中对疫苗抗原的免疫球蛋白G反应上级，并且在使用双氯芬酸的5小时内，大鼠爪肿胀减少70%，而皮肤组织学无变化，证明了贴片的体内效用。
Needleless delivery into the skin would overcome a major barrier to efficient clinical utilization of advanced therapies such as nanomaterials and macromolecules. This study demonstrates that controlled skin stretching (in porcine, rat, and mouse models) using a patch comprising a hypobaric chamber, to open the skin appendages, can increase the permeability of the tissue and provide a means to enable direct delivery of advanced therapies directly into the skin without the use of a needle or injection system. This technology can facilitate the self-administration of therapeutics including vaccines, RNA, and antigens, thus improving the translation of these products into effective clinical use. Advanced therapies are commonly administered via injection even when they act within the skin tissue, and this increases the chances of off-target effects. Here we report the use of a skin patch containing a hypobaric chamber that induces skin dome formation to enable needleless delivery of advanced therapies directly into porcine, rat, and mouse skin. Finite element method modeling showed that the hypobaric chamber in the patch opened the skin appendages by 32%, thinned the skin, and compressed the appendage wall epithelia. These changes allowed direct delivery of an H1N1 vaccine antigen and a diclofenac nanotherapeutic into the skin. Fluorescence imaging and infrared mapping of the skin showed needleless delivery via the appendages. The in vivo utility of the patch was demonstrated by a superior immunoglobulin G response to the vaccine antigen in mice compared to intramuscular injection and a 70% reduction in rat paw swelling in vivo over 5 h with diclofenac without skin histology changes.
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影响因子：
3.4
作者：
Cross, SE;Anderson, C;Roberts, MS
通讯作者：
Roberts, MS
影响因子：
3.4
作者：
Boncheva, Mila;Damien, Fabienne;Normand, Valery
通讯作者：
Normand, Valery
DOI：
10.1016/j.jconrel.2016.01.052
发表时间：
2016-03-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Inacio R;Poland S;Cai XJ;Cleary SJ;Ameer-Beg S;Keeble J;Jones SA
通讯作者：
Jones SA
DOI：
10.1016/j.ejpb.2016.03.002
发表时间：
2016-05
期刊：
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
影响因子：
--
作者：
Inacio R;Barlow D;Kong X;Keeble J;Jones SA
通讯作者：
Jones SA
影响因子：
5.8
作者：
Cai, X. J.;Patel, T.;Jones, S. A.
通讯作者：
Jones, S. A.