Evaluation of the clinical impact of repeat application of hydrogel-forming microneedle array patches

Abstract

Hydrogel-forming microneedle array patches (MAPs) have been proposed as viable clinical tools for patient monitoring purposes, providing an alternative to traditional methods of sample acquisition, such as venepuncture and intradermal sampling. They are also undergoing investigation in the management of non-melanoma skin cancers. In contrast to drug or vaccine delivery, when only a small number of MAP applications would be required, hydrogel MAPs utilised for sampling purposes or for tumour eradication would necessitate regular, repeat applications. Therefore, the current study was designed to address one of the key translational aspects of MAP development, namely patient safety. We demonstrate, for the first time in human volunteers, that repeat MAP application and wear does not lead to prolonged skin reactions or prolonged disruption of skin barrier function. Importantly, concentrations of specific systemic biomarkers of inflammation (C-reactive protein (CRP); tumour necrosis factor-α (TNF-α)); infection (interleukin-1β (IL-1β); allergy (immunoglobulin E (IgE)) and immunity (immunoglobulin G (IgG)) were all recorded over the course of this fixed study period. No biomarker concentrations above the normal, documented adult ranges were recorded over the course of the study, indicating that no systemic reactions had been initiated in volunteers. Building upon the results of this study, which serve to highlight the safety of our hydrogel MAP, we are actively working towards CE marking of our MAP technology as a medical device.

Hydrogel‐Forming Microneedles: Current Advancements and Future Trends

“…However, there is currently no extensive research into the biocompatibility of HFMs; it should be mentioned that there are examples of work that have demonstrated in vivo operation over a prolonged period (see Section 4.5 for the details of clinical trials). [ 57 ]…”

“…Recently, gold nanorods (GnRs) have been incorporated into HFMs to aid the treatment of nonmelanoma skin cancers using near‐infrared radiation. [ 57,91 ] Superficial nonmelanoma skin cancer refers to a group of skin cancers that slowly develop in the upper layers of the skin. Currently, established and effective methods of treatment include topical imiquimod, 5‐fluorouracil, and photodynamic therapy but these come with side effects, such as burning pain, blistering, and dermatitis.…”

“…To date, preclinical studies have been carried out for HFMs, as previously discussed throughout, but there are limited examples of HFMs used in clinical trials. However, one example is from Al‐Kasasbeh et al., [ 57 ] who successfully implemented HFMs in a clinical setting, by repeating the application of HFM arrays formed of PMVE/MA crosslinked with PEG ( M W of 10 kDa). They found that during repeated usage, no measurable amounts of polymer was present in the visible skin layers, with the resultant visual marks after removal of the HFMs quickly disappearing with no evidence of application 18 h after removal.…”

Recent advances in combination of microneedles and nanomedicines for lymphatic targeted drug delivery

“…The majority of hydrogel‐forming MN arrays described in the literature are made predominantly of a combination of poly(methyl‐vinyl ether‐co‐maleic anhydride) and poly(ethylene glycol) accomplished by a cross‐linking reaction. It is important to note, that the use of this type of MN arrays has been shown to be safe when applied repeatedly into animals and human volunteers (Al‐Kasasbeh et al, 2020; Vicente‐Perez et al, 2017).…”

From the laboratory to the end-user: a primary packaging study for microneedle patches containing amoxicillin sodium

“…Regarding patient safety, there is evidence to show that hydrogel-forming MN arrays exhibit no microbial growth, pose a very low risk to human health [3,[14][15][16] and cause no adverse side effects [17][18][19], even when repeatedly applied to the same human volunteers, every day for 5 days [20]. It was shown, for the first time, in human volunteers that repeat application and wear of hydrogel-forming MN arrays, prolonged skin reactions, or disruption of the skin barrier function did not occur and the normal balance of key systemic biomarkers over a fixed study period was not disrupted [20]. Although the commercial success of MN arrays will ultimately depend on the end-user, an important aspect that must be considered is if MN patches will be 'fit for purpose' when they reach the end-user.…”