Long-term intraarticular delivery of glucocorticoids from novel particles

Glucocorticoids (GCs) are potent anti-inflammatory and analgesic treatments in musculoskeletal diseases and when delivered intraarticularly in arthritic joints they are amongst the most effective treatments.

However, GCs are rapidly released from current depot formulations which are crystalline suspensions or polymer complexes so the beneficial effects do not persist much beyond a few weeks/months.

We have manufactured a new formulation where GC crystals are incorporated into microchamber film arrays (MFA) produced by a soft lithography method.

Preliminary data shows that release of the GC dexamethasone from MFA is very slow with the majority of the drug retained after 8 or 12 weeks in release experiments. Whilst we have previously prepared MFA with other cargo molecules their rate of release has been more rapid. We have also recently developed methods to convert MFA into individual microcapsules.

In the studies in this proposal we will explore the influence of microchamber structure, shape, size and polymer wall thickness on GC release rate.

We will then convert GC MFA into individual separated microcapsules to form a suspension of them and monitor and compare GC release rate with other formulations currently used in the clinic.

Preclinical data will also be obtained in this study from experiments in mice where GC microcapsules delivered into stifle joints will be assessed for biocompatibility, retention and GC release into joints and blood through the use of a sensitive cell assay we have developed.

The proportion of the released and remaining GC in the joint will be assessed at intervals up to 6 months after delivery. At the end of the proposed work we anticipate that we should be close to assessment in clinical trials.

Although GCs are an established treatment in localised arthritis we anticipate that their prolonged delivery from the microcapsules proposed will represent a step change in this treatment modality making their use more convenient and cost effective.

In terms of Versus Arthritis an improved local treatment for arthritic disease is in line with their aim to support the development of breakthrough treatments for musculoskeletal diseases.