title: Microneedle-mediated transdermal bacteriophage delivery.
abstract: 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 × 10(6)PFU/ml (plaque forming units per ml) was detected in the receiver compartment when delivered across dermatomed skin and 4.0 × 10(3)PFU/ml was detected in the receiver compartment when delivered across full thickness skin. An in vivo study resulted in 4.13 × 10(3)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 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.
authors: School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors: Elizabeth
authors: E
authors: Ryan
authors: Martin J
authors: MJ
authors: Garland
authors: Thakur Raghu Raj
authors: TR
authors: Singh
authors: Eoin
authors: E
authors: Bambury
authors: John
authors: J
authors: O'Dea
authors: Katarzyna
authors: K
authors: Migalska
authors: Sean P
authors: SP
authors: Gorman
authors: Helen O
authors: HO
authors: McCarthy
authors: Brendan F
authors: BF
authors: Gilmore
authors: Ryan F
authors: RF
authors: Donnelly
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000831:Animals, Newborn; D017122:Bacteriophage T4; D004926:Escherichia coli; D008297:Male; D008845:Microinjections; D009339:Needles; D011076:Polycarboxylate Cement; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine
chemical_list: D011076:Polycarboxylate Cement; C005506:polycarbonate