Hydrogel-forming microneedles enhance transdermal delivery of metformin hydrochloride.
Hydrogel-forming microneedles enhance transdermal delivery of metformin hydrochloride.
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DOI：
10.1016/j.jconrel.2018.07.009
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发表时间：
2018-09-10
期刊：
影响因子：
--
通讯作者：
Donnelly RF
中科院分区：
文献类型：
--
作者：
Migdadi EM;Courtenay AJ;Tekko IA;McCrudden MTC;Kearney MC;McAlister E;McCarthy HO;Donnelly RF
我们首次研究了形成水凝胶的微针(MN)贴片以持续的方式经皮给药高剂量盐酸二甲双胍的可能性。这可以最大限度地减少与口服有关的一些胃肠道副作用和小肠吸收变化。贴片(两层)由冻干药物储存层组装而成，MN层由20%w/w聚(甲基乙烯醚-马来酸)通过酯化而与7.5%w/w聚乙二醇10,000 Da的水混合物制成。>；90%的二甲双胍是从均质药物储集层中回收的。药库在pH 7.4PBS中的溶解时间为<；10 min。MN始终渗透到经过验证的皮肤模型Parafilm®M中。MN可促进盐酸二甲双胍在体外新生猪皮肤中的渗透。MN和盐酸二甲双胍(含75 mg和50 mg盐酸二甲双胍)在6 h分别释放9.71 ± 2.22 mg和10.04 ± 1.92 mg，24 h分别释放28.15 ± 2.37 mg和23.25 ± 3.58 mg。相比之下，在6 h分别释放0.34 ± 0.39 mg和0.85 ± 0.68 mg。在24 h分别给药0.39 ± 0.39 mg和1.01 ± 0.84 mg，分别来自仅使用药物储存库的对照装置。体内给药后1 h，大鼠血浆中可检测到盐酸二甲双胍，浓度为0.6 2 ± 0.5 1 μg/m L，3 h时升至3.76 ± 2.5 8 μg/m l，24 h达最大值3.77 ± 2.0 9 μg/m l，Css为3.2 g/m L。盐酸二甲双胍透皮吸收的生物利用度估计为30%。水凝胶形成微球是一种很有前途的技术，已证明盐酸二甲双胍经皮给药成功。显然，使用该系统给药其他大剂量药物是有潜力的。
We investigated, for the first time, the potential for a hydrogel-forming microneedle (MN) patch to deliver the high-dose drug metformin HCl transdermally in a sustained manner. This may minimize some gastrointestinal side effects and small intestine absorption variations associated with oral delivery. Patches (two layers) were assembled from a lyophilised drug reservoir layer, with the MN layer made from aqueous blend of 20% w/w poly (methylvinylether-co-maleic acid) crosslinked by esterification with 7.5% w/w poly (ethylene glycol) 10,000 Da. >90% of metformin was recovered from homogeneous drug reservoirs. Drug reservoir dissolution time in PBS (pH 7.4) was <10 min. MN penetrated a validated skin model Parafilm® M consistently. Permeation of metformin HCl across dermatomed neonatal porcine skin in vitro was enhanced by using MN. The combined MN and metformin HCl reservoir patch (containing 75 mg or 50 mg metformin HCl, respectively) delivered 9.71 ± 2.22 mg and 10.04 ± 1.92 mg at 6 h, respectively, and 28.15 ± 2.37 mg and 23.25 ± 3.58 mg at 24 h, respectively.In comparison, 0.34 ± 0.39 mg and 0.85 ± 0.68 mg was delivered at 6 h, respectively, and 0.39 ± 0.39 mg and 1.01 ± 0.84 mg was delivered at 24 h, respectively, from a control set-up employing only the drug reservoirs. In vivo, metformin HCl was detected in rat plasma at 1 h post MN application at a concentration of 0.62 ± 0.51 μg/mL, increasing to 3.76 ± 2.58 μg/ml at 3 h. A maximal concentration of 3.77 ± 2.09 μg/ml was achieved at 24 h. Css was 3.2 μg/mL. Metformin transdermal bioavailability using MNs was estimated as 30%.Hydrogel-forming MN are a promising technology that has demonstrated successful transdermal delivery of metformin HCl. Potential clearly exists for administration of other high-dose drugs using this system.
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影响因子：
5.5
作者：
Bogachus, Lindsey D.;Turcotte, Lorraine P.
通讯作者：
Turcotte, Lorraine P.
影响因子：
19
作者：
Donnelly, Ryan F.;Singh, Thakur Raghu Raj;Garland, Martin J.;Migalska, Katarzyna;Majithiya, Rita;McCrudden, Cian M.;Kole, Prashant Laxman;Mahmood, Tuan Mazlelaa Tuan;McCarthy, Helen O.;Woolfson, A. David
通讯作者：
Woolfson, A. David
影响因子：
2.6
作者：
Gong L;Goswami S;Giacomini KM;Altman RB;Klein TE
通讯作者：
Klein TE
影响因子：
3.7
作者：
Donnelly RF;McCrudden MT;Zaid Alkilani A;Larrañeta E;McAlister E;Courtenay AJ;Kearney MC;Singh TR;McCarthy HO;Kett VL;Caffarel-Salvador E;Al-Zahrani S;Woolfson AD
通讯作者：
Woolfson AD
影响因子：
5.8
作者：
Carter, D;Howlett, HCS;Bailey, CJ
通讯作者：
Bailey, CJ