Research Projects

Psoriasis is a chronic inflammatory disease affecting over 60 million people worldwide and 2.8% of the Indian population. The clinical manifestations include keratinocyte hyperproliferation-based thickening of the epidermis and the development of red, itchy, scaly patches. Current treatment strategies in psoriasis management include topical agents such as vitamin D analogs, corticosteroids, anti-inflammatory cytokine inhibitors, and monoclonal antibodies. However, the demerits of these strategies, such as limited efficacy and off-target toxicity upon long-term use, push the need to develop new techniques. Emerging evidence strongly supports that the stimulator of the interferon genes (STING) pathway is an intracellular signaling molecule. This project proposes a novel strategy combining the 'poke and release' mechanism of the dissolvable microneedles and keratinocytes targeting reactive oxygen species (ROS)-responsive nanoparticles to inhibit the expression of STING. This unique combination aims to overcome the shortcomings of conventional therapies by ensuring localized, targeted delivery of STING inhibitors in the psoriatic lesions. We hypothesized that a microneedle patch consisting of ROS-responsive hydrogel and keratinocyte-targeting ROS-responsive nanoparticles would be an effective psoriasis treatment. Objective 1: To synthesize and characterize reactive oxygen species responsive (ROS) hydrogels. Objective 2: Synthesis and characterization of CD 44 targeting, ROS responsive nanoparticles loaded with STING inhibitor. Objective 3: Fabrication of the microneedle using ROS-responsive hydrogel integrated with CD 44 targeting, ROS-responsive nanoparticles. Objective 4: In Vitro Evaluation of Biocompatibility and Targeting Efficiency. Objective 5:In vivo efficacy and safety of microneedles patch in Psoriasis Animal Models. Objective 6: In vivo efficacy and safety of microneedle patches in prophylactic psoriasis-animal model. Main Experiments: 1) Synthesis and characterization of ROS-responsive hydrogels. 2) Synthesis of keratinocyte targeting ROS-responsive nanoparticle loaded with STING-inhibitor, H-151. 3)Fabrication of microneedle patch using ROS-responsive hydrogels and keratinocyte targeting nanoparticles 4) In vitro studies for cytotoxicity, targeted uptake, and STING pathway inhibition in fibroblasts and keratinocytes. 5) In vivo efficacy testing in a mouse psoriasis model, assessing the therapeutic effect of MN patches on skin inflammation and STING inhibition.6) Prophylactic studies to evaluate the potential of MN patches to prevent the onset of psoriasis. With the successful development of the microneedle patch with its potential to significantly improve drug delivery and minimize side effects, a new, minimally invasive, effective, patient-friendly treatment option would be availed to psoriatic patients. In addition, this platform has the potential for broader application in other inflammatory diseases beyond psoriasis.

Psoriasis, inflammation, Reactive Oxygen Species (ROS), Dissolvable Microneedles, Targeted Drug Delivery, Nanoparticles