Periodic Reporting for period 1 - DesiRTA (Localize and Controlled co-delivery of AuNPs conjugated siRNA by Cationic Shear-thinning Gel Matrix for Treatment of Arthritis (DesiRTA))
Reporting period: 2024-04-01 to 2026-03-31
DesiRTA: A Targeted Nanotherapeutic Approach for Revolutionizing Arthritis Treatment
Arthritis, a prevalent global health concern affecting over 350 million individuals, substantially burdens healthcare systems. This chronic condition, characterized by joint pain, edema, and restricted mobility, significantly impairs patients' quality of life and contributes considerably to work disability. Current therapeutic interventions, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs), often yield suboptimal efficacy and are associated with undesirable side effects, such as osteoporosis and hyperglycemia. Consequently, there is an urgent clinical need for safer, more effective, and targeted treatment modalities.
DesiRTA (Localized and Controlled co-delivery of AuNPs conjugated siRNA by Cationic Shear-thinning Gel Matrix for Treatment of Arthritis) endeavors to address this unmet need by developing a novel therapeutic strategy employing gold nanoparticles (AuNPs) and small interfering RNA (siRNA). siRNA demonstrates significant therapeutic promise by selectively silencing genes implicated in arthritis progression. However, its clinical translation is limited by challenges such as enzymatic degradation and suboptimal cellular internalization. DesiRTA overcomes these limitations by conjugating siRNA with AuNPs. These AuNPs protect against degradation and enhance cellular uptake and exhibit inherent anti-inflammatory properties. The resulting AuNP-siRNA conjugates are further stabilized and delivered via an innovative shear-thinning hydrogel. This biocompatible hydrogel, engineered to mimic synovial fluid, facilitates facile injection and enables sustained release of the therapeutic payload directly into the affected joint.
The DesiRTA project follows a structured pathway to impact, encompassing several key stages. Initially, a library of stable AuNP-siRNA biopolymer complexes will be generated. Subsequently, the shear-thinning injectable hydrogel carrier will be synthesized. Finally, the formulation's release kinetics, stability, and in-vitro and in-vivo performance will be rigorously assessed. DesiRTA's innovative approach offers several potential breakthroughs: the development of ultra-stable AuNP-siRNA conjugates for sustained and controlled delivery, a tailored shear-thinning hydrogel matrix for localized treatment, and the synergistic action of AuNPs and siRNA to simultaneously modulate multiple disease-modifying factors. By mitigating in-vivo siRNA degradation and enabling targeted gene silencing, DesiRTA can potentially transform arthritis therapy.
Arthritis, a prevalent global health concern affecting over 350 million individuals, substantially burdens healthcare systems. This chronic condition, characterized by joint pain, edema, and restricted mobility, significantly impairs patients' quality of life and contributes considerably to work disability. Current therapeutic interventions, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs), often yield suboptimal efficacy and are associated with undesirable side effects, such as osteoporosis and hyperglycemia. Consequently, there is an urgent clinical need for safer, more effective, and targeted treatment modalities.
DesiRTA (Localized and Controlled co-delivery of AuNPs conjugated siRNA by Cationic Shear-thinning Gel Matrix for Treatment of Arthritis) endeavors to address this unmet need by developing a novel therapeutic strategy employing gold nanoparticles (AuNPs) and small interfering RNA (siRNA). siRNA demonstrates significant therapeutic promise by selectively silencing genes implicated in arthritis progression. However, its clinical translation is limited by challenges such as enzymatic degradation and suboptimal cellular internalization. DesiRTA overcomes these limitations by conjugating siRNA with AuNPs. These AuNPs protect against degradation and enhance cellular uptake and exhibit inherent anti-inflammatory properties. The resulting AuNP-siRNA conjugates are further stabilized and delivered via an innovative shear-thinning hydrogel. This biocompatible hydrogel, engineered to mimic synovial fluid, facilitates facile injection and enables sustained release of the therapeutic payload directly into the affected joint.
The DesiRTA project follows a structured pathway to impact, encompassing several key stages. Initially, a library of stable AuNP-siRNA biopolymer complexes will be generated. Subsequently, the shear-thinning injectable hydrogel carrier will be synthesized. Finally, the formulation's release kinetics, stability, and in-vitro and in-vivo performance will be rigorously assessed. DesiRTA's innovative approach offers several potential breakthroughs: the development of ultra-stable AuNP-siRNA conjugates for sustained and controlled delivery, a tailored shear-thinning hydrogel matrix for localized treatment, and the synergistic action of AuNPs and siRNA to simultaneously modulate multiple disease-modifying factors. By mitigating in-vivo siRNA degradation and enabling targeted gene silencing, DesiRTA can potentially transform arthritis therapy.
During the reporting period, functional biomaterials and hydrogel-forming systems were synthesised and investigated for nanoparticle and controlled-delivery applications. Gold nanoparticle-conjugated siRNA nanocomplexes were prepared and characterised using DLS and TEM. Stability studies were performed to assess suitability for hydrogel loading. The AuNP–siRNA nanocomplexes were incorporated into injectable hydrogel matrices and release was evaluated over approximately 80 h. In vitro biological evaluation using the MHA7 cell line and ELISA showed an anti-inflammatory response, supporting the feasibility of the DesiRTA concept. The project also generated two peer-reviewed publications in related hydrogel/biomaterial areas and one poster presentation acknowledging DesiRTA support.
DesiRTA progressed beyond conventional systemic anti-inflammatory delivery approaches by integrating AuNP–siRNA nanocomplexes with an injectable hydrogel depot designed for localised and sustained therapeutic delivery. The project combined nanoparticle formulation, hydrogel loading, controlled release and in vitro anti-inflammatory assessment within one biomaterial-assisted platform. Related published outputs further demonstrated progress in injectable stimuli-responsive hydrogels, controlled drug release, tissue-interfacing biomaterials and biocompatible hemostatic materials.