Hydrogel-forming microneedles prepared from "super swelling" polymers combined with lyophilised wafers for transdermal drug delivery.
Hydrogel-forming microneedles prepared from "super swelling" polymers combined with lyophilised wafers for transdermal drug delivery.
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DOI：
10.1371/journal.pone.0111547
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Woolfson AD
中科院分区：
文献类型：
--
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
我们首次描述了由“超溶胀”聚合物组合物制备的水凝胶形成微针阵列。我们从含有20%w/w Gantrez S-97、7.5%w/w PEG 10，000和3%w/w Na 2CO 3的水性共混物中制备了具有增强的溶胀能力的微针制剂，并使用了冻干晶片样设计的药物贮库。这些微针冻干的薄片组合物是稳健的并且有效地穿透皮肤，广泛地溶胀，但被完整地去除。在穿过切除的新生猪皮肤的体外递送实验中，在24小时内递送了约44 mg的模型高剂量小分子药物布洛芬钠，相当于冻干储器中37%的负载。超溶胀微针在24小时内递送约1.24 mg模型蛋白卵清蛋白，相当于约49%的递送效率。集成的微针-冻干片递送系统在大鼠中产生了布洛芬钠的血浆浓度在6小时内逐渐增加，此时达到的最大浓度约为179 µg/ml。24 h时血浆浓度降至71±6.7 µg/ml。仅1小时后大鼠血浆中的卵清蛋白水平达到峰值，为42.36±17.01 ng/ml。然后卵清蛋白血浆水平几乎保持恒定，直至6小时，在24小时略有下降，检测到23.61±4.84 ng/ml。这项工作代表了传统微针系统的重大进步，目前仅适用于非常有效的药物和疫苗的推注输送。一旦充分开发，这种技术可能会大大扩大可透皮给药的药物范围，从而使患者和行业受益。因此，我们目前正在对一系列候选分子进行临床评价。
We describe, for the first time, hydrogel-forming microneedle arrays prepared from “super swelling” polymeric compositions. We produced a microneedle formulation with enhanced swelling capabilities from aqueous blends containing 20% w/w Gantrez S-97, 7.5% w/w PEG 10,000 and 3% w/w Na2CO3 and utilised a drug reservoir of a lyophilised wafer-like design. These microneedle-lyophilised wafer compositions were robust and effectively penetrated skin, swelling extensively, but being removed intact. In in vitro delivery experiments across excised neonatal porcine skin, approximately 44 mg of the model high dose small molecule drug ibuprofen sodium was delivered in 24 h, equating to 37% of the loading in the lyophilised reservoir. The super swelling microneedles delivered approximately 1.24 mg of the model protein ovalbumin over 24 h, equivalent to a delivery efficiency of approximately 49%. The integrated microneedle-lyophilised wafer delivery system produced a progressive increase in plasma concentrations of ibuprofen sodium in rats over 6 h, with a maximal concentration of approximately 179 µg/ml achieved in this time. The plasma concentration had fallen to 71±6.7 µg/ml by 24 h. Ovalbumin levels peaked in rat plasma after only 1 hour at 42.36±17.01 ng/ml. Ovalbumin plasma levels then remained almost constant up to 6 h, dropping somewhat at 24 h, when 23.61±4.84 ng/ml was detected. This work represents a significant advancement on conventional microneedle systems, which are presently only suitable for bolus delivery of very potent drugs and vaccines. Once fully developed, such technology may greatly expand the range of drugs that can be delivered transdermally, to the benefit of patients and industry. Accordingly, we are currently progressing towards clinical evaluations with a range of candidate molecules.
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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：
3.7
作者：
Migalska, Katarzyna;Morrow, Desmond I. J.;Donnelly, Ryan F.
通讯作者：
Donnelly, Ryan F.
DOI：
10.2147/dddt.s44401
发表时间：
2013
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Hong X;Wei L;Wu F;Wu Z;Chen L;Liu Z;Yuan W
通讯作者：
Yuan W
影响因子：
3
作者：
WOOLFSON, AD;MCCAFFERTY, DF;ANDERSON, JM
通讯作者：
ANDERSON, JM
影响因子：
3.3
作者：
McCrudden, Maelosa T. C.;Torrisi, Barbara M.;Donnelly, Ryan F.
通讯作者：
Donnelly, Ryan F.