Delivery of large molecules via microneedles and self-gelating biodegradable hydrogels for the treatment of degenerative bone conditions

Abstract

Osteoarthritis is a debilitating condition affecting millions globally; it is an ever-expanding problem, due in no small part to an aging population and the growing obesity crisis. As humans grow older, joint degeneration is inevitable, and as people live longer these problems will commensurately increase. Compounding these problems with an obesity epidemic further exacerbates the problem with more damage being realised at even young ages.

Despite the prevalence of this condition, no cure exists to date. Currently, a range of treatments are used to alleviate related symptoms, with treatments including interarticular administration of steroids, and dietary supplementation. To date, the value of these treatments is a cause for debate, resulting in the absence of a consensus between regulatory bodies, particularly with respect to the use of dietary supplements.

Supplements which are most commonly taken by patients with osteoarthritis include chondroitin sulfate and glucosamine sulfate, both of which are classed as nutraceuticals rather than pharmaceuticals, and as such, are not subject to the stringent regulations surrounding pharmaceutical products. Rather, they are required to meet food grade standards, essentially indicating that they are safe to consume, but do not have to meet regulations with respect to aspects such as strength of dosing. The nature of these regulatory requirements leads to myriad of issues with respect to these products, including the availability of preparations which contain massively different ranges of the therapeutic agent. As such, it is hardly surprising that the results from clinical trials centred on the use of these products are mixed, with in many cases, investigated products taking the form of a placebo.

The project presented here focuses on a range of aims, including the development of a robust method for the quantification of chondroitin sulfate, which at present, is known to be challenging, as a result of analytical methods currently being used being unfit for purpose for a range of reasons, including a lack of discrimination, and sensitivity.

A further strand of work within the project centres on the development for the enhancement of bioavailability of chondroitin sulfate which is particularly low when administered via the oral route, due to factors including poor permeation, and first-pass metabolic processes. As such, the work presented here will look to develop sound approaches for the administration to the affected joint directly, or within the systemic circulation, such that intestinal barriers are circumvented. These approaches have involved the utilisation of a range of polymers, including those which exhibit thermoresponsive effects, such that the systems in question can bring about sustained and controlled delivery of therapeutic.

Work within this part of the project involved substantial rheological characterisation, permitting more to be understood about these properties of the identified system, particularly in relation to factors such as shear stress, temperature, and presence of drug, with the latter permitting conclusions to be drawn with respect to practical drug loading capabilities. Drug release studies were also utilised to learn more about the drug release profiles of these systems, in turn providing further information in relation to their feasibility.

Date of Award	Dec 2020
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Engineering & Physical Sciences Research Council
Supervisor	Ryan Donnelly (Supervisor), Colin McCoy (Supervisor) & David Rooney (Supervisor)