Evaluation of physical and chemical modifications to drug reservoirs for stimuli-responsive microneedles

Hydrogel-forming microneedle (MN) arrays are minimally-invasive devices that can penetrate the stratum corneum, the main barrier to topical drug application, without causing pain. However, drug delivery using hydrogel-forming MN arrays tends to be relatively slow compared to rapid drug delivery using conventional needles and syringes. Therefore, in this work, for the first time, different physical and chemical delivery enhancement methods were employed in combination with PVA-based hydrogel-forming MN arrays. Using a model drug, ibuprofen (IBU) sodium, the designed systems were assessed in terms of the extent of transdermal delivery. Iontophoresis (ITP) and heat-assisted drug delivery technology were investigated as physical permeation enhancement techniques. Ex vivo studies demonstrated that the ITP (0.5 mA/cm²)-mediated combination strategy significantly enhanced the transdermal permeation of IBU sodium over the first 6 h (~ 5.11 mg) when compared to MN alone (~ 1.63 mg) (p < 0.05). In contrast, heat-assisted technology showed almost no promoting effect on transdermal delivery. Furthermore, IBU sodium-containing rapidly dissolving lyophilised and effervescent reservoirs, classified as chemical modification methods, were prepared. Both strategies achieved rapid and effective ex vivo IBU sodium permeation, equating to ~ 78% (30.66 mg) and ~ 71% (28.43 mg) from lyophilised and effervescent reservoirs, respectively. Moreover, in vivo pharmacokinetic studies showed that the IBU sodium plasma concentration within lyophilised and effervescent groups reached a maximum concentration (C_max) at 4 h (~ 282.15 µg/mL) and 6 h (~ 140.81 µg/mL), respectively. These strategies not only provided rapid achievement of therapeutic levels (10-15 µg/ml), but also resulted in sustained release of IBU sodium for at least 48 h, which could effectively reduce the frequency of administration, thereby improving patient compliance and reducing side effects of IBU sodium.