Current Status of Gout Arthritis: Current Approaches to Gout Arthritis Treatment: Nanoparticles Delivery Systems Approach

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(1), P. 102 - 102

Published: Jan. 14, 2025

The deposition of monosodium urate (MSU) crystals within joint spaces produces a painful inflammatory condition known as gout, specific form arthritis. calls for combined curative and preventive management model. A new development in the approach to gout is that NLRP3-targeted biologic agents, such monoclonal therapies, provide more accurate treatment by blocking pro-inflammatory cytokines. Nanoparticle drug delivery enhances biological availability targets, which may increase therapeutic efficacy decrease general toxicity. again cannot be ignored, mainly keeping up certain modifications diet weight, along with pharmacological therapies reduce uric acid (UA) levels frequency acute attacks. advancement genetic profiling patients biomarker discoveries drives trend towards building individualized medicine care, quickly gaining ground most effective method delivering treatments individual patients, moving away from one-size-fits-all treatments. following paper aims an updated account focus on recent developments, order enhance these approaches, quality life standard treatment.

Language: Английский

Nanourchin‐like Uricase‐Poly(_L‐proline) Conjugate with Retained Enzymatic Activity, Mitigated Immunogenicity, and Sustained Efficacy Upon Repeated Administrations

Angewandte Chemie International Edition, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

The poor half-life and strong immunogenicity of proteins such as uricase (UOx), a therapeutic enzyme for chronic refractory gout hyperuricemia, are pressing clinical challenges. Although conjugation poly(ethylene glycol) (PEGylation) UOx can improve the pharmacokinetics, preexisting or induced anti-PEG antibodies, which lead to accelerate blood clearance (ABC) reduced response rate, have been major hurdle. Herein, we report facile "grafting-from" preparation nanourchin-like uricase-poly(L-proline) conjugate, namely UOx-PLP, with high grafting-density, enhanced thermal, lyophilization, freeze-thaw, proteolytic stability. Through transient preblocking strategy in synthesis, UOx-PLP overcomes activity loss retains ~82 % activity. In Sprague-Dawley rats, stimulates minimum complement activation anti-UOx antibodies. Unlike PEG-UOx gave significantly after repetitive administrations, shows no sign ABC effect. Moreover, remain almost unchanged when cross-administrated rats previously received titers Finally, efficacy five straight administrations knock-out hyperuricemia mice model, whereas experiences sharp upon same treatment. Overall, simple outstanding nonclinical results highlight enormous potential future translation.

Language: Английский

Nanourchin‐like Uricase‐Poly(_L‐proline) Conjugate with Retained Enzymatic Activity, Mitigated Immunogenicity, and Sustained Efficacy Upon Repeated Administrations

Angewandte Chemie, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Abstract The poor half‐life and strong immunogenicity of proteins such as uricase (UOx), a therapeutic enzyme for chronic refractory gout hyperuricemia, are pressing clinical challenges. Although conjugation poly(ethylene glycol) (PEGylation) UOx can improve the pharmacokinetics, preexisting or induced anti‐PEG antibodies, which lead to accelerate blood clearance (ABC) reduced response rate, have been major hurdle. Herein, we report facile “grafting‐from” preparation nanourchin‐like uricase‐poly( L ‐proline) conjugate, namely UOx‐PLP, with high grafting‐density, enhanced thermal, lyophilization, freeze‐thaw, proteolytic stability. Through transient preblocking strategy in synthesis, UOx‐PLP overcomes activity loss retains ~82 % activity. In Sprague‐Dawley rats, stimulates minimum complement activation anti‐UOx antibodies. Unlike PEG‐UOx gave significantly after repetitive administrations, shows no sign ABC effect. Moreover, remain almost unchanged when cross‐administrated rats previously received titers Finally, efficacy five straight administrations knock‐out hyperuricemia mice model, whereas experiences sharp upon same treatment. Overall, simple outstanding nonclinical results highlight enormous potential future translation.

Language: Английский