Hydrogel-Forming Microneedle Arrays Made from Light-Responsive Materials for On-Demand Transdermal Drug Delivery

Abstract

We describe, for the first time, stimulus-responsive hydrogel-forming microneedle (MN) arrays that enable delivery of a clinically relevant model drug (ibuprofen) upon application of light. MN arrays were prepared using a polymer prepared from 2-hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) by micromolding. The obtained MN arrays showed good mechanical properties. The system was loaded with up to 5% (w/w) ibuprofen included in a light-responsive 3,5-dimethoxybenzoin conjugate. Raman spectroscopy confirmed the presence of the conjugate inside the polymeric MN matrix. In vitro, this system was able to deliver up to three doses of 50 mg of ibuprofen upon application of an optical trigger over a prolonged period of time (up to 160 h). This makes the system appealing as a controlled release device for prolonged periods of time. We believe that this technology has potential for use in "on-demand" delivery of a wide range of drugs in a variety of applications relevant to enhanced patient care.

Biomedical Applications of Polymeric Microneedles for Transdermal Therapeutic Delivery and Diagnosis: Current Status and Future Perspectives

“…[54,55] The substrate materials for the preparation of hydrogel microneedles mainly include PVA, poly(methyl vinyl ether-co-maleic acid) (PMVE-co-MA), acrylate modified HA (m-HA), and poly(2-hydroxyethyl methacrylate) (PHEMA). [56][57][58] It is worth noting that the cross-linking process of polymers usually involves high temperature or UV exposure, [59] it is necessary to protect the loaded protein drugs from disruption throughout the fabrication process by loading drugs into the base postmolding instead of the microneedle tip during cross-linking process. [60] Furthermore, it should be noted that swellable microneedles require fine tuning of the cross-linking density so as to possess sufficient mechanical strength in the dry state to pierce the stratum corneum.…”

“…McCoy et al reported the preparation of a UV lightresponsive drug-releasing polyhydroxyethyl methacrylate hydrogel microneedle. [59] The photo-responsive ibuprofen conjugate was immobilized in the microneedle matrix via non-covalent bonds, and the drug was trapped inside the microneedle without illumination. Upon UV illumination, the ibuprofen conjugate disintegrated and generated a water-soluble ibuprofen.…”

Spatially and temporally controlled hydrogels for tissue engineering

“…Hardy et al described the development of stimuli-responsive needles based on hydrogels, which could control the release of ibuprofen via external light application [212]. The hydrogel needles were fabricated using a micromolding technique using HEMA and ethylene glycol dimethacrylate monomers along with ibuprofen and a light-responsive 3,5-dimethoxybenzoin conjugate to trigger drug release.…”

“…The system was able to deliver 3 doses of ibuprofen over an extended period of time upon programmed light exposure. Ultrasound-triggered delivery systems have been developed using alginate hydrogels that displayed self-healing abilities after ultrasound pulses, which allowed on-demand delivery of mitoxantrone to breast cancer xenografts in mice to suppress tumor growth and reduce tumor size [212]. Thermo-responsive hydrogels using N -isopropylacrylamide and 1-vinyl-2-pyrrolidinone monomers have been synthesized for on-demand delivery of diclofenac sodium and procaine hydrochloride [206].…”

Bioresponsive transcutaneous patches

“…Compared to delivery systems triggered by external stimuli like electric field [14,15], light [16,17], or mechanical force [18], the MN patches activated by a physiological signal provide self-regulated delivery of drug in response to the abnormal physiological signals, thereby maximizing therapeutic efficiency and minimizing side effects or toxicity [19]. …”