Feasibility study of carbon nanotube microneedles for rapid transdermal drug delivery

We introduce a new approach for fabricating hollow microneedles using vertically-aligned carbon nanotubes (VA-CNTs) for rapid transdermal drug delivery. Here, we discuss the fabrication of the microneedles emphasizing the overall simplicity and flexibility of the method to allow for potential industrial application. By capitalizing on the nanoporosity of the CNT bundles, uncured polymer can be wicked into the needles ultimately creating a high strength composite of aligned nanotubes and polymer. Flow through the microneedles as well as in vitro penetration of the microneedles into swine skin is demonstrated. Furthermore, we present a trade study comparing the difficulty and complexity of the fabrication process of our CNT-polymer microneedles with other standard microneedle fabrication approaches. Copyright © Materials Research Society 2013.

An investigation of the stability and diffusivity of flexible lipid vesicles for transdermal insulin delivery

Gemstone Team No More Needles

Hydrogel-Forming Microneedle Arrays for Enhanced Transdermal Drug Delivery

Unique microneedle arrays prepared from crosslinked polymers, which contain no drug themselves, are described. They rapidly take up skin interstitial fluid upon skin insertion to form continuous, unblockable, hydrogel conduits from attached patch-type drug reservoirs to the dermal microcirculation. Importantly, such microneedles, which can be fabricated in a wide range of patch sizes and microneedle geometries, can be easily sterilized, resist hole closure while in place, and are removed completely intact from the skin. Delivery of macromolecules is no longer limited to what can be loaded into the microneedles themselves and transdermal drug delivery is now controlled by the crosslink density of the hydrogel system rather than the stratum corneum, while electrically modulated delivery is also a unique feature. This technology has the potential to overcome the limitations of conventional microneedle designs and greatly increase the range of the type of drug that is deliverable transdermally, with ensuing benefits for industry, healthcare providers and, ultimately, patients.

Fast-drying multi-laminate bioadhesive films for transdermal and topical drug delivery

No bioadhesive patch-based system is currently marketed. This is despite an extensive number of literature reports on such systems detailing their advantages over conventional pressure sensitive adhesive-based patches in wet environments and describing successful delivery of a diverse array of drug substances. This lack of proprietary bioadhesive patches is largely due to the fact that such systems are exclusively water-based, meaning drying is difficult. In this paper we describe, for the first time, a novel multiple lamination method for production of bioadhesive patches. In contrast to patches produced using a conventional casting approach, which took 48 hours to dry, bioadhesive films prepared using the novel multiple lamination method were dried in 15?min and were folded into formed patches in a further 10?min. Patches prepared by both methods had comparable physicochemical properties. The multiple lamination method allowed supersaturation of 5-aminolevulinic acid to be achieved in formed patch matrices. However, drug release studies were unable to show an advantage for supersaturation with this particular drug, due to its water high solubility. The multiple lamination method allowed greater than 90% of incorporated nicotine to remain within formed patches, in contrast to the 48% achieved for patches prepared using a conventional casting approach. The procedure described here could readily be adapted for automation by industry. Due to the reduced time, energy and ensuing finance now required, this could lead to bioadhesive patch-based drug delivery systems becoming commercially viable. This would, in turn, mean that pathological conditions occurring in wet or moist areas of the body could now be routinely treated by prolonged site-specific drug delivery, as mediated by a commercially produced bioadhesive patch.

Microneedles for intradermal and transdermal drug delivery

The formidable barrier properties of the uppermost layer of the skin, the stratum corneum, impose significant limitations for successful systemic delivery of broad range of therapeutic molecules particularly macromolecules and genetic material. Microneedle (MN) has been proposed as a strategy to breach the stratum corneum barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves use of micron sized needles fabricated of different materials and geometries to create transient aqueous conduits across the skin. MN, alone or with other enhancing strategies, has been demonstrated to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo experiments. This suggested the promising use of MN technology for various possible clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. MN has been proved as minimally invasive and painless in human subjects. This review article focuses on recent and future developments for MN technology including the latest type of MN design, challenges and strategies in MNs development as well as potential safety aspects based on comprehensive literature review pertaining to MN studies to date. (C) 2013 Elsevier B.V. All rights reserved.

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

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.

Microwave-Assisted Preparation of Hydrogel-Forming Microneedle Arrays for Transdermal Drug Delivery Applications

A microwave (MW)-assisted crosslinking process to prepare hydrogel-forming microneedle (MN) arrays was evaluated. Conventionally, such MN arrays are prepared using processes that includes a thermal crosslinking step. Polymeric MN arrays were prepared using poly(methyl vinyl ether-alt-maleic acid) crosslinked by reaction with poly(ethylene glycol) over 24 h at 80 °C. Polymeric MN arrays were prepared to compare conventional process with the novel MW-assisted crosslinking method. Infrared spectroscopy was used to evaluate the crosslinking degree, evaluating the area of the carbonyl peaks (2000–1500 cm−1). It was shown that, by using the MW-assisted process, MN with a similar crosslinking degree to those prepared conventionally can be obtained in only 45 min. The effects of the crosslinking process on the properties of these materials were also evaluated. For this purpose swelling kinetics, mechanical characterisation, and insertion studies were performed. The results suggest that MN arrays prepared using the MW assisted process had equivalent properties to those prepared conventionally but can be produced 30 times faster. Finally, an in vitro caffeine permeation across excised porcine skin was performed using conventional and MW-prepared MN arrays. The release profiles obtained can be considered equivalent, delivering in both cases 3000–3500 μg of caffeine after 24 h.

Novel Delivery Systems for Transdermal and Intradermal Drug Delivery

This research book covers the major aspects relating to the use of novel delivery systems in enhancing both transdermal and intradermal drug delivery. It provides a review of transdermal and intradermal drug delivery, including the history of the field and the various methods employed to produce delivery systems from different materials such as device design, construction and evaluation, so as to provide a sound background to the use of novel systems in enhanced delivery applications.

Furthermore, it presents in-depth analyses of recent developments in this exponentially growing field, with a focus on microneedle arrays, needle-free injections, nanoparticulate systems and peptide-carrier-type systems. It also covers conventional physical enhancement strategies, such as tape-stripping, sonophoresis, iontophoresis, electroporation and thermal/suction/laser ablation Discussions about the penetration of the stratum corneum by the various novel strategies highlight the importance of the application method. Comprehensive and critical reviews of transdermal and intradermal delivery research using such systems focus on the outcomes of in vivoanimal and human studies. The book includes laboratory, clinical and commercial case studies featuring safety and patient acceptability studies carried out to date, and depicts a growing area for use of these novel systems is in intradermal vaccine delivery. The final chapters review recent patents in this field and describe the work ongoing in industry.