Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis.
Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis.
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DOI：
10.1016/j.jconrel.2017.07.032
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发表时间：
2017-11-10
期刊：
影响因子：
--
通讯作者：
Donnelly RF
中科院分区：
文献类型：
--
作者：
González-Vázquez P;Larrañeta E;McCrudden MTC;Jarrahian C;Rein-Weston A;Quintanar-Solares M;Zehrung D;McCarthy H;Courtenay AJ;Donnelly RF
新生儿感染是低资源环境中儿童死亡的主要原因。世界卫生组织关于新生儿和幼儿可能严重细菌感染（PSBI）的门诊治疗指南（当转诊到医院治疗不可行时）包括肌内注射庆大霉素（GEN）和口服阿莫西林。GEN以瓶装或安瓿装硫酸庆大霉素水溶液的形式提供，要求医护人员接受剂量计算或根据患者体重范围选择适当剂量的培训，并获得安全的注射用品和适当的锐器处置。在低资源环境中治疗PSBI的简化配方，包装和交付方法可以减少用户错误，并扩大新生儿期严重感染婴儿的救命门诊抗生素治疗。我们开发了溶解聚合物微针（MN）阵列以经皮递送GEN。MN阵列由含有30%（w/w）GEN和两种由美国食品和药物管理局批准的聚合物的水性共混物产生：透明质酸钠和聚（乙烯基吡咯烷酮）。阵列（19 × 19针和500 μm高）机械强度高，能够穿透皮肤模拟物至378 μm的深度。使用Franz Cell装置在体外测试MN阵列，在6小时内递送约4.45 mg GEN。最后，在动物模型中测试由MN阵列递送的三种不同剂量（低、中和高）的GEN。GEN的最大血浆水平呈剂量依赖性，范围为2 - 5 μg/mL。MN阵列应用后达到这些水平所需的时间范围为1至6小时。这项工作证明了溶解MN阵列在体内以治疗水平经皮递送GEN的潜力。
Neonatal infections are a leading cause of childhood mortality in low-resource settings. World Health Organization guidelines for outpatient treatment of possible serious bacterial infection (PSBI) in neonates and young infants when referral for hospital treatment is not feasible include intramuscular gentamicin (GEN) and oral amoxicillin. GEN is supplied as an aqueous solution of gentamicin sulphate in vials or ampoules and requires health care workers to be trained in dose calculation or selection of an appropriate dose based on the patient's weight band and to have access to safe injection supplies and appropriate sharps disposal. A simplified formulation, packaging, and delivery method to treat PSBI in low-resource settings could decrease user error and expand access to lifesaving outpatient antibiotic treatment for infants with severe infection during the neonatal period. We developed dissolving polymeric microneedles (MN) arrays to deliver GEN transdermally. MN arrays were produced from aqueous blends containing 30% (w/w) of GEN and two polymers approved by the US Food and Drug Administration: sodium hyaluronate and poly(vinylpyrrolidone). The arrays (19 × 19 needles and 500 μm height) were mechanically strong and were able to penetrate a skin simulant to a depth of 378 μm. The MN arrays were tested in vitro using a Franz Cell setup delivering approximately 4.45 mg of GEN over 6 h. Finally, three different doses (low, medium, and high) of GEN delivered by MN arrays were tested in an animal model. Maximum plasma levels of GEN were dose-dependent and ranged between 2 and 5 μg/mL. The time required to reach these levels post-MN array application ranged between 1 and 6 h. This work demonstrated the potential of dissolving MN arrays to deliver GEN transdermally at therapeutic levels in vivo.
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影响因子：
5.5
作者：
Edens C;Collins ML;Goodson JL;Rota PA;Prausnitz MR
通讯作者：
Prausnitz MR
影响因子：
3.8
作者：
Donnelly, Ryan F.;Mooney, Karen;Mccrudden, Maeliosa T. C.;Vicente-Perez, Eva M.;Belaid, Luc;Gonzalez-Vazquez, Patricia;Mcelnay, James C.;Woolfson, A. David
通讯作者：
Woolfson, A. David
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：
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
DOI：
10.1016/j.jconrel.2010.10.033
发表时间：
2011-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Chu LY;Prausnitz MR
通讯作者：
Prausnitz MR