Microneedle-mediated transdermal bacteriophage delivery

• Published in: European journal of pharmaceutical sciences 2012-09, Vol.47 (2), p.297-304
• Main Authors: Ryan, Elizabeth, Garland, Martin J., Singh, Thakur Raghu Raj, Bambury, Eoin, O’Dea, John, Migalska, Katarzyna, Gorman, Sean P., McCarthy, Helen O., Gilmore, Brendan F., Donnelly, Ryan F.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Animals; Animals, Newborn; Bacterial infection; Bacteriophage T4; Bacteriophage therapy; Biological and medical sciences; Escherichia coli; General pharmacology; Hollow microneedle; Male; Medical sciences; Microinjections; Needles; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polycarboxylate Cement; Rats; Rats, Sprague-Dawley; Swine; Transdermal delivery
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2012.06.012

Images of PC hollow MN arrays using a variety of microscopy techniques (a) Digital microscope images of single MN and a section of the MN array (b) SEM images of a single MN, the bore of the MN and a section of the MN array (c) X-ray microtomography images of single MNs, the bore of the MN and the Mn array (d) He-ion images of a single MN, illustrating the bore of the needle and a radial view of the MN. [Display omitted] 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 2.67×106PFU/ml (plaque forming units per ml) was detected in the receiver compartment when delivered across dermatomed skin and 4.0×103PFU/ml was detected in the receiver compartment when delivered across full thickness skin. An in vivo study resulted in 4.13×103PFU/ml being detected in blood 30min following initial MN-mediated phage administration. Clearance occurred rapidly, with phages being completely cleared from the systemic circulation within 24h, 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.