METHOD: Therefore, there is a need to improve delivery of therapeutic macromolecules to enable non-invasive delivery routes, less frequent dosing through controlled-release drug delivery, and improved drug targeting to increase efficacy and reduce side effects.

RESULT: Non-invasive administration routes such as intranasal, pulmonary, transdermal, ocular and oral delivery have been attempted intensively by formulating macromolecules into nanoparticulate carriers system such as polymeric and lipidic nanoparticles.

METHODS: This study, involving a series of N-of-1 trials, included 21 participants who had a history of neuropathic plantar forefoot ulcers. Participants were recruited from two public hospitals and one private podiatry clinic in Sydney, New South Wales, Australia. This trial is non-randomised and unblinded. Participants will be recruited from three sites, including two high-risk foot services and a private podiatry clinic in Sydney, Australia. Mobilemat™ and F-Scan® plantar pressure mapping systems by TekScan® (Boston, USA) will be used to measure barefoot and in-shoe plantar pressures. Participants' self-reports will be used to quantify the wearing period over a certain period of between 2 and 4 weeks during the trial. Participant preference toward footwear, insole design and quality-of-life-related information will be collected and analysed. The descriptive and inferential statistical analyses will be performed using IBM SPSS Statistics (version 27). And the software NVivo (version 12) will be utilised for the qualitative data analysis.

DISCUSSION: This is the first trial assessing footwear and insole interventions in people with diabetes by using a series of N-of-1 trials. Reporting self-declared wearing periods and participants' preferences on footwear style and aesthetics are the important approaches for this trial. Patient-centric device designs are the key to therapeutic outcomes, and this study is designed with that strategy in mind.