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

Autor: Li L; School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, BT9 7BL, Belfast, United Kingdom., Anjani QK; School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, BT9 7BL, Belfast, United Kingdom., Hutton ARJ; School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, BT9 7BL, Belfast, United Kingdom.; School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine, United Kingdom, Block Y, 1SA, Cromore Rd, BT52 1SA., Li M; School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, BT9 7BL, Belfast, United Kingdom., Sabri AHB; School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, BT9 7BL, Belfast, United Kingdom., Vora L; School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, BT9 7BL, Belfast, United Kingdom., Naser YA; School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, BT9 7BL, Belfast, United Kingdom., Tao Y; School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, BT9 7BL, Belfast, United Kingdom., McCarthy HO; School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, BT9 7BL, Belfast, United Kingdom., Donnelly RF; School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, BT9 7BL, Belfast, United Kingdom. r.donnelly@qub.ac.uk.
Jazyk: angličtina
Zdroj: Drug delivery and translational research [Drug Deliv Transl Res] 2024 Nov 20. Date of Electronic Publication: 2024 Nov 20.
DOI: 10.1007/s13346-024-01737-0
Abstrakt: 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/cm 2 )-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.
Competing Interests: Declarations. Ethics approval and consent to participate:  All institutional and national guidelines for the care and use of laboratory animals were followed.  Consent for publication : All authors have approved the final version of the manuscript.  Competing interest:  Ryan Donnelly is an inventor of patents that have been licensed to companies developing microneedle-based products and is a paid advisor to companies developing microneedle-based products. The resulting potential conflict of interest has been disclosed and is managed by Queen’s University Belfast. The companies had no role in the design of the manuscript, in the collection, analyses, or interpretation of the various studies reviewed, in the writing of the manuscript, or in the decision to publish.  All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2024. The Author(s).)
Databáze: MEDLINE
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