Hydrogel-Forming Microneedles Prepared from “Super Swelling” Polymers Combined with Lyophilised Wafers for Transdermal Drug Delivery

• Published in: PloS one Vol. 9; no. 10; p. e111547
• Main Authors: Donnelly, Ryan F., McCrudden, Maelíosa T. C., Zaid Alkilani, Ahlam, Larrañeta, Eneko, McAlister, Emma, Courtenay, Aaron J., Kearney, Mary-Carmel, Singh, Thakur Raghu Raj, McCarthy, Helen O., Kett, Victoria L., Caffarel-Salvador, Ester, Al-Zahrani, Sharifa, Woolfson, A. David
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.10.2014; Public Library of Science (PLoS)
• Subjects: Acids; Administration, Cutaneous; Animals; Animals, Newborn; Biology and Life Sciences; Chickens; Composition effects; Cross-Linking Reagents - chemistry; Drug delivery; Drug delivery systems; Drug Delivery Systems - methods; Drug development; Drug dosages; Drugs; Forming; Freeze Drying; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Hydrogels; Ibuprofen; Ibuprofen - pharmacology; International economic relations; Materials Testing; Medicine and Health Sciences; Microinjections; Mixtures; Needles; Neonates; Ovalbumin; Permeability - drug effects; Pharmacy; Physical Sciences; Plasma levels; Polyethylene glycol; Polymer industry; Polymers; Polymers - chemistry; Rats; Rats, Sprague-Dawley; Research and Analysis Methods; Skin; Sodium; Sus scrofa; Swelling; Transdermal medication; Vaccines; Web sites; Websites; United Kingdom > UK; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0111547

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.