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.

Evaluation of transverse piezoelectric coefficient of ZnO thin films deposited on different flexible substrates: a comparative study on the vibration sensing performance.

We report on the systematic comparative study of highly c-axis oriented and crystalline piezoelectric ZnO thin films deposited on four different flexible substrates for vibration sensing application. The flexible substrates employed for present experimental study were namely a metal alloy (Phynox), metal (aluminum), polyimide (Kapton), and polyester (Mylar). ZnO thin films were deposited by an RF reactive magnetron sputtering technique. ZnO thin films of similar thicknesses of 700 ± 30 nm were deposited on four different flexible substrates to have proper comparative studies. The crystallinity, surface morphology, chemical composition, and roughness of ZnO thin films were evaluated by respective material characterization techniques. The transverse piezoelectric coefficient (d31) value for assessing the piezoelectric property of ZnO thin films on different flexible substrates was measured by a four-point bending method. ZnO thin films deposited on Phynox alloy substrate showed relatively better material characterization results and a higher piezoelectric d31 coefficient value as compared to ZnO films on metal and polymer substrates. In order to experimentally verify the above observations, vibration sensing studies were performed. As expected, the ZnO thin film deposited on Phynox alloy substrate showed better vibration sensing performance. It has generated the highest peak to peak output voltage amplitude of 256 mV as compared to that of aluminum (224 mV), Kapton (144 mV), and Mylar (46 mV). Therefore, metal alloy flexible substrate proves to be a more suitable, advantageous, and versatile choice for integrating ZnO thin films as compared to metal and polymer flexible substrates for vibration sensing applications. The present experimental study is extremely important and helpful for the selection of a suitable flexible substrate for various applications in the field of sensor and actuator technology.