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

Ryan F. Donnelly, Maeliosa T. C. McCrudden, Ahlam Zaid Alkilani, Eneko Larraneta, Emma McAlister, Aaron J. Courtenay, Mary-Carmel Kearney, Thakur Raghu Raj Singh, Helen O. McCarthy, Victoria L. Kett, Ester Caffarel-Salvador, Sharifa Al-Zahrani, A. David Woolfson

Research output: Contribution to journalArticle

93 Citations (Scopus)

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.
LanguageEnglish
JournalPLoS ONE
Volume9
Issue number10
DOIs
Publication statusPublished - 31 Oct 2014

Cite this

Donnelly, Ryan F. ; McCrudden, Maeliosa T. C. ; Alkilani, Ahlam Zaid ; Larraneta, 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. / Hydrogel-Forming Microneedles Prepared from "Super Swelling'' Polymers Combined with Lyophilised Wafers for Transdermal Drug Delivery. In: PLoS ONE. 2014 ; Vol. 9, No. 10.
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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.",
author = "Donnelly, {Ryan F.} and McCrudden, {Maeliosa T. C.} and Alkilani, {Ahlam Zaid} and Eneko Larraneta and Emma McAlister and Courtenay, {Aaron J.} and Mary-Carmel Kearney and Singh, {Thakur Raghu Raj} and McCarthy, {Helen O.} and Kett, {Victoria L.} and Ester Caffarel-Salvador and Sharifa Al-Zahrani and Woolfson, {A. David}",
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Donnelly, RF, McCrudden, MTC, Alkilani, AZ, Larraneta, E, McAlister, E, Courtenay, AJ, Kearney, M-C, Singh, TRR, McCarthy, HO, Kett, VL, Caffarel-Salvador, E, Al-Zahrani, S & Woolfson, AD 2014, 'Hydrogel-Forming Microneedles Prepared from "Super Swelling'' Polymers Combined with Lyophilised Wafers for Transdermal Drug Delivery', PLoS ONE, vol. 9, no. 10. https://doi.org/10.1371/journal.pone.0111547

Hydrogel-Forming Microneedles Prepared from "Super Swelling'' Polymers Combined with Lyophilised Wafers for Transdermal Drug Delivery. / Donnelly, Ryan F.; McCrudden, Maeliosa T. C.; Alkilani, Ahlam Zaid; Larraneta, 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.

In: PLoS ONE, Vol. 9, No. 10, 31.10.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hydrogel-Forming Microneedles Prepared from "Super Swelling'' Polymers Combined with Lyophilised Wafers for Transdermal Drug Delivery

AU - Donnelly, Ryan F.

AU - McCrudden, Maeliosa T. C.

AU - Alkilani, Ahlam Zaid

AU - Larraneta, Eneko

AU - McAlister, Emma

AU - Courtenay, Aaron J.

AU - Kearney, Mary-Carmel

AU - Singh, Thakur Raghu Raj

AU - McCarthy, Helen O.

AU - Kett, Victoria L.

AU - Caffarel-Salvador, Ester

AU - Al-Zahrani, Sharifa

AU - Woolfson, A. David

PY - 2014/10/31

Y1 - 2014/10/31

N2 - 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.

AB - 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.

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DO - 10.1371/journal.pone.0111547

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JO - PLoS ONE

T2 - PLoS ONE

JF - PLoS ONE

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