Microneedle-mediated transdermal bacteriophage delivery

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• 作者：Elizabeth Ryan ; Martin J. Garl ; Thakur Raghu Raj Singh ; Eoin Bambury ; John O¡¯Dea ; Katarzyna Migalska ; Sean P. Gorman ; Helen O. McCarthy ; Brendan F. Gilmore ; Ryan F. Donnelly
• 关键词：Bacteriophage therapy ; Transdermal delivery ; Hollow microneedle ; Bacterial infection
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2012
• 出版时间：29 September, 2012
• 年：2012
• 卷：47
• 期：2
• 页码：297-304
• 全文大小：803 K

文摘

Interest in bacteriophages as therapeutic agents has recently been reawakened. Parenteral delivery is the most routinely-employed method of administration. However, injection of phages has numerous disadvantages, such as the requirement of a health professional for administration and the possibility of cross-contamination. Transdermal delivery offers one potential means of overcoming many of these problems. The present study utilized a novel poly (carbonate) (PC) hollow microneedle (MN) device for the transdermal delivery of Escherichia coli-specific T4 bacteriophages both in vitro and in vivo. MN successfully achieved bacteriophage delivery in vitro across dermatomed and full thickness skin. A concentration of 2.67 ¡Á 10⁶ PFU/ml (plaque forming units per ml) was detected in the receiver compartment when delivered across dermatomed skin and 4.0 ¡Á 10³ PFU/ml was detected in the receiver compartment when delivered across full thickness skin. An in vivo study resulted in 4.13 ¡Á 10³ PFU/ml being detected in blood 30 min following initial MN-mediated phage administration. Clearance occurred rapidly, with phages being completely cleared from the systemic circulation within 24 h, which was expected in the absence of infection. We have shown here that MN-mediated delivery allows successful systemic phage absorption. Accordingly, bacteriophage-based therapeutics may now have an alternative route for systemic delivery. Once fully-investigated, this could lead to more widespread investigation of these interesting therapeutic viruses.