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.

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent

“…[49][50][51][52] On the other hand, Donnelly et al used "super swelling" microneedles made of hydrogel forming polymers (Gantrez S-97, polyethylene glycol and Na 2 CO 3 ) to deliver 0.32 g OVA across the skin of Sprague Dawley rats. [53] A peak plasma concentration of OVA was observed in 1 h that was sustained for another 5 h. These studies suggest that microneedles are one of the promising tools for enhancement of transdermal delivery for several types of macro molecules. Colloidal formulations have also been shown to enhance transdermal skin penetration.…”

Microneedle characterisation: the need for universal acceptance criteria and GMP specifications when moving towards commercialisation

“…They have been produced from a variety of materials such as glass [16], sugar [17], metal [18], metal coated [19], silicon [14], solid polymer [20], aqueous hydrogel [21] and dissolving polymers [15]. MN have been fabricated using a diversity of techniques, mostly from microelectromechanical systems (MEMS) technology.…”

Microneedle Manufacture: Assessing Hazards and Control Measures

“…There are five principal classes of microneedle used for drug delivery applications: solid, drug coated solid, hollow, dissolvable, and swellable [1][2][3][8][9][10][11][12][13][14][15][16][17][18][19]. The fabrication of solid MN arrays is procedurally the simplest approach and can be constructed from a variety of conventional and inexpensive polymers such as polystyrene, polycarbonate, and polymethylmethacrylate [8][9][10][11][12].…”

“…It is only when the needles are subjected to an aqueous environment, particularly alkaline conditions, that the needle swells and their mechanical strength is reduced through gradual dissolution (Figure 3B-D). The dissolvable and swellable systems can be formed from a wide variety of polymer systems with the dissolution rate controlled through the particular formulation employed [15][16][17][18][19]. The scope and intricacies of the latter have been comprehensively reviewed elsewhere [1][2][3] and the compositions exploited in this work are principally used as model systems.…”

“…There are numerous advantages to the adoption of dissolvable or swellable MNs and, in many respects, they represent the least risk in terms of accidental needlestick and the transmission of BBPs. Upon penetration of the skin, they are effectively self-disarming as their piercing capability is generally lost through the process of dissolution or swelling [15][16][17][18][19].…”