title: Hydrogel-forming microneedle arrays exhibit antimicrobial properties: potential for enhanced patient safety.
abstract: We describe, for the first time, the microbial characterisation of hydrogel-forming polymeric microneedle arrays and the potential for passage of microorganisms into skin following microneedle penetration. Uniquely, we also present insights into the storage stability of these hydroscopic formulations, from physical and microbiological viewpoints, and examine clinical performance and safety in human volunteers. Experiments employing excised porcine skin and radiolabelled microorganisms showed that microorganisms can penetrate skin beyond the stratum corneum following microneedle puncture. Indeed, the numbers of microorganisms crossing the stratum corneum following microneedle puncture were greater than 10⁵ cfu in each case. However, no microorganisms crossed the epidermal skin. When using a 21G hypodermic needle, more than 10⁴ microorganisms penetrated into the viable tissue and 10⁶ cfu of Candida albicans and Staphylococcus epidermidis completely crossed the epidermal skin in 24 h. The hydrogel-forming materials contained no microorganisms following de-moulding and exhibited no microbial growth during storage, while also maintaining their mechanical strength, apart from when stored at relative humidities of 86%. No microbial penetration through the swelling microneedles was detectable, while human volunteer studies confirmed that skin or systemic infection is highly unlikely when polymeric microneedles are used for transdermal drug delivery. Since no pharmacopoeial standards currently exist for microneedle-based products, the exact requirements for a proprietary product based on hydrogel-forming microneedles are at present unclear. However, we are currently working towards a comprehensive specification set for this microneedle system that may inform future developments in this regard.
authors: School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK. r.donnelly@qub.ac.uk
authors: Ryan F
authors: RF
authors: Donnelly
authors: Thakur Raghu Raj
authors: TR
authors: Singh
authors: Ahlam Zaid
authors: AZ
authors: Alkilani
authors: Maelíosa T C
authors: MT
authors: McCrudden
authors: Shannon
authors: S
authors: O'Neill
authors: Conor
authors: C
authors: O'Mahony
authors: Keith
authors: K
authors: Armstrong
authors: Nabla
authors: N
authors: McLoone
authors: Prashant
authors: P
authors: Kole
authors: A David
authors: AD
authors: Woolfson
mesh_terms: D000328:Adult; D000818:Animals; D002176:Candida albicans / Q000378:metabolism*; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006813:Humidity; D020100:Hydrogels; D008297:Male; D009339:Needles; D010539:Permeability; D011108:Polymers / Q000737:chemistry; D012867:Skin / Q000378:metabolism* / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000378:metabolism*; D013552:Swine; D013997:Time Factors; D055815:Young Adult
chemical_list: D020100:Hydrogels; D011108:Polymers
references: J Control Release. 2010 Nov 1;147(3):333-41
references: 20727929
references: Pharm Res. 2001 Jul;18(7):1006-11
references: 11496937
references: Pharm Res. 2009 Nov;26(11):2513-22
references: 19756972
references: J Am Acad Dermatol. 2006 Mar;54(3):458-65
references: 16488297
references: Med J Aust. 2001 Mar 19;174(6):306
references: 11297122
references: Drug Dev Ind Pharm. 2009 Oct;35(10):1242-54
references: 19555249
references: Expert Opin Drug Deliv. 2012 May;9(5):541-50
references: 22475249
references: Biofabrication. 2012 Mar;4(1):011002
references: 22287512
references: Pharm Res. 2011 Jan;28(1):41-57
references: 20490627
references: AAPS PharmSciTech. 2007 Jan 19;8(1):2
references: 17408218
references: Adv Funct Mater. 2012 Dec 5;22(23):4879-4890
references: 23606824
references: Lancet Infect Dis. 2006 Oct;6(10):641-52
references: 17008173
references: Curr Probl Dermatol. 2006;33:35-41
references: 16766879
references: Photochem Photobiol. 1989 Dec;50(6):771-84
references: 2626491
references: Pharm Res. 2011 Aug;28(8):1919-30
references: 21437789
references: Int Immunopharmacol. 2007 Apr;7(4):464-72
references: 17321469