A NOVEL TRANSDERMAL HYDROGEL-FORMING MICRONEEDLES PATCH A PROMISING SYSTEM TO DELIVER METHOTREXATE FOR JIA PATIENTS: In-vivo study

Research output: Contribution to conferencePoster

Abstract

Introduction:
Methotrexate (MTX) is a cornerstone of therapy worldwide for juvenile idiopathic arthritis [1], yet its current drug delivery systems (oral and subcutaneous) are still challenging and associated with serious side effects. Transderaml route is an attractive alternative drug delivery route, yet the outer layer of the skin presents a strong barrier for transdermal permeation of such
drug (MTX is hydrophilic and its log P -1.85). In a previous in-vitro study [3], a novel PVA-based hydrogel-forming microneedles (HF-MNs) array was developed and showed to be a promising efficient transdermal delivery system for MTX. However, its application in an in-vivo setting (rat model), suggested further optimisation is required to form more rigid and strong MNs and special
patch design is needed to make its application feasible.
Objectives:
To optimise PVA-based HF-MNs array properties to improve its rigidity and develop a special HF-MNs patch design loaded with the required MTX dose and evaluate its efficiency to deliver MTX in an in-vivo setting.
Methods:
HF-MN arrays composed of 11 x 11 MNs of conical shape with MNs measuring (729.5 um) in height, 300 um in width at the baseplate and interspacing 200-250 um were fabricated and optimised to form a stronger HF-MNs array. The
fabricated HF-MNs arrays were characterised in terms of their mechanical strength, swelling capacity and permeability to MTX in an in-vitro setting employing Franz-type diffusion cells. The optimised HF-MNs arrays were then used to build up a novel HF-MNs patch loaded with MTX dose of 5 mg/kg. The ability of the fabricated HF-MNs patch to deliver MTX in an in-vivo setting was
evaluated using Sprague Dawley rats (n= 6). One patch was applied onto the back of each rat with 20 uL of deionised water added into the MTX wafer reservoir and then removed after 24 hours. 200 L blood samples were collected over 48 hours from application at predetermined time intervals and then analysed for MTX and its polyglutamates (PGs) content.
Results:
The optimised HF-MNs arrays showed superior properties in terms of their mechanical strength and swelling capacity in comparison with those reported in previous study [3]. Upon applying the HF-MNs patch onto skin at the back of the rat, MNs were inserted into skin without breaking or bending. Furthermore, upon removing the patch. Also, it was noticed that HF-MNs completely
swelled and the MTX wafer was dissolved indicating that the HF-MNs after insertion into skin imbibed skin interstitial fluid forming continuous conduits between the dermal microcirculation and an attached MTX wafer reservoir within the patch. This allowed the drug to be delivered in a controlled sustained manner. Interestingly, the HF-MNs arrays were removed intact from skin and no marks of irritation or severe inflammation were observed at the application site.
Conclusion:
The optimised PVA-based HF-MNs with the novel patch design has shown to be a promising, minimally invasive transdermal drug delivery system which could be used to deliver MTX efficiently to JIA patients. However, further investigation is
required to prove its efficiency and safety and advantage in comparison with other administration routes (oral, subcutaneous) after single and multiple application using larger number if rats.
Original languageEnglish
Publication statusPublished - 16 Sep 2017
EventPReS: The 24th PReS Congress - Athens, Greece
Duration: 14 Sep 201717 Sep 2017
http://www.pres.eu/pres2017/

Conference

ConferencePReS
CountryGreece
CityAthens
Period14/09/201717/09/2017
Internet address

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