Methotrexate delivering microneedle patches for improved therapeutic efficacy in treatment of rheumatoid arthritis.

Arthritis is an inflammatory disorder that leads to degeneration and swelling in the joints thereby severely affecting mobility. Till date, a complete cure for this disorder remains elusive. Administration of disease modifying anti-rheumatic drugs has not proved effective owing to poor retention of drugs at the site of inflammation in the joints. In most cases, lack of adherence to the therapeutic regimen further aggravates the condition. Localized administration of the drugs through intra-articular injections is highly invasive and painful. A possible solution to overcome these issues will be to ensure sustained release of the anti-arthritic drug at the site of inflammation through a minimally invasive method. The present work focuses on the development of a microneedle patch for localized and minimally invasive delivery of methotrexate to arthritic joints in guinea pig model. The microneedle patch was found to elicit minimal immune response and ensured sustained release of the drug that was manifested through faster restoration of mobility and a distinct reduction in inflammatory and rheumatoid markers at the joints when compared to untreated and those treated through conventional hypodermic injections. Our results demonstrate the promise of microneedle-based platform for an effective arthritic therapy.

Single step fabrication of hollow microneedles and an experimental package for controlled drug delivery.

Hollow microneedle arrays (HMNs) are an excellent choice for managing chronic diseases requiring the administration of multiple drug doses over a prolonged duration. However, HMNs have gained partial success due to limitations in their manufacturing capabilities, and cumbersome processes. In the present study, polymeric HMNs were fabricated using a novel single-step drop-casting process without needing cleanroom facilities, and sophisticated instrumentation. When drop casted on the pyramidal tip stainless steel needles, the optimized polymer solution allowed the reproducible formation of desired height HMMs on a detachable acrylic base. To enable broader applications, the base with HMNs was integrated into an experimental package built to deliver a dose of âˆ¼ 5 µL per 30° clockwise rotation of the actuator, allowing multiple metered drug dose administrations. The fabricated HMNs were optically imaged, and tested for mechanical integrity and stability. The working and functional utility of the HMNs package in delivering metered drug doses was demonstrated by delivering vitamin B12 (ex vivo) and insulin (in vivo), respectively. The optimized process can be used for the large-scale manufacturing of HMNs and the experimental package shows the potential to be further developed into a wearable device.