title: Hydrogel-forming microneedles prepared from "super swelling" polymers combined with lyophilised wafers for transdermal drug delivery.
abstract: We describe, for the first time, hydrogel-forming microneedle arrays prepared from "super swelling" polymeric compositions. We produced a microneedle formulation with enhanced swelling capabilities from aqueous blends containing 20% w/w Gantrez S-97, 7.5% w/w PEG 10,000 and 3% w/w Na2CO3 and utilised a drug reservoir of a lyophilised wafer-like design. These microneedle-lyophilised wafer compositions were robust and effectively penetrated skin, swelling extensively, but being removed intact. In in vitro delivery experiments across excised neonatal porcine skin, approximately 44 mg of the model high dose small molecule drug ibuprofen sodium was delivered in 24 h, equating to 37% of the loading in the lyophilised reservoir. The super swelling microneedles delivered approximately 1.24 mg of the model protein ovalbumin over 24 h, equivalent to a delivery efficiency of approximately 49%. The integrated microneedle-lyophilised wafer delivery system produced a progressive increase in plasma concentrations of ibuprofen sodium in rats over 6 h, with a maximal concentration of approximately 179 µg/ml achieved in this time. The plasma concentration had fallen to 71±6.7 µg/ml by 24 h. Ovalbumin levels peaked in rat plasma after only 1 hour at 42.36±17.01 ng/ml. Ovalbumin plasma levels then remained almost constant up to 6 h, dropping somewhat at 24 h, when 23.61±4.84 ng/ml was detected. This work represents a significant advancement on conventional microneedle systems, which are presently only suitable for bolus delivery of very potent drugs and vaccines. Once fully developed, such technology may greatly expand the range of drugs that can be delivered transdermally, to the benefit of patients and industry. Accordingly, we are currently progressing towards clinical evaluations with a range of candidate molecules.
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Co. Antrim, United Kingdom.
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Co. Antrim, United Kingdom.
authors.forename: Maelíosa T C
authors.initials: MT
authors.lastname: McCrudden
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Co. Antrim, United Kingdom; School of Pharmacy, Zarqa University, Zarqa, Jordan.
authors.forename: Ahlam
authors.initials: A
authors.lastname: Zaid Alkilani
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Co. Antrim, United Kingdom.
authors.forename: Eneko
authors.initials: E
authors.lastname: Larrañeta
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Co. Antrim, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: McAlister
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Co. Antrim, United Kingdom.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Courtenay
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Co. Antrim, United Kingdom.
authors.forename: Mary-Carmel
authors.initials: MC
authors.lastname: Kearney
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Co. Antrim, United Kingdom.
authors.forename: Thakur Raghu Raj
authors.initials: TR
authors.lastname: Singh
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Co. Antrim, United Kingdom.
authors.forename: Helen O
authors.initials: HO
authors.lastname: McCarthy
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Co. Antrim, United Kingdom.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Kett
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Co. Antrim, United Kingdom.
authors.forename: Ester
authors.initials: E
authors.lastname: Caffarel-Salvador
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Co. Antrim, United Kingdom.
authors.forename: Sharifa
authors.initials: S
authors.lastname: Al-Zahrani
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Co. Antrim, United Kingdom.
authors.forename: A David
authors.initials: AD
authors.lastname: Woolfson
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000831:Animals, Newborn; D002645:Chickens; D003432:Cross-Linking Reagents / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005612:Freeze Drying; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007052:Ibuprofen / Q000494:pharmacology*; D008422:Materials Testing; D008845:Microinjections; D009339:Needles; D010539:Permeability / Q000187:drug effects; D011108:Polymers / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D034421:Sus scrofa
chemical_list: D003432:Cross-Linking Reagents; D011108:Polymers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007052:Ibuprofen