Microneedle-assisted dual delivery of PUMA gene and celastrol for synergistic therapy of rheumatoid arthritis through restoring synovial homeostasis

Bioactive Materials, Год журнала: 2024, Номер 36, С. 83 - 95

Опубликована: Март 1, 2024

Abnormal proliferation of aggressive fibroblast-like synoviocytes (FLS) and perpetuate synovial inflammation can inevitably accelerate the progression rheumatoid arthritis (RA). Herein, a strategy simultaneously promoting FLS apoptosis inhibiting as mediated by macrophages is proposed to restore homeostasis for effective RA therapy. A hyaluronic acid-based dissolvable microneedle (MN) fabricated transdermal delivery dual human serum albumin (HSA)-contained biomimetic nanocomplexes regulate macrophages. Upon skin insertion, are released rapidly from MN accumulate in joint microenvironment through both passive active targeting HSA. Thioketal-crosslinked fluorinated polyethyleneimine 1.8 K (TKPF) was constructed bind plasmid encoding pro-apoptotic gene PUMA with HSA coating layer (TKPF/pPUMA@HSA, TPH). TPH upregulate transfection trigger efficient apoptosis. Also, encapsulating classic anti-inflammatory natural product celastrol (Cel@HSA, CH) inhibit blocking NF-κB pathway activation. TPH/CH deplete M1 macrophage activation, suppress hyperplasia well reduce bone cartilage erosion collagen-induced (CIA) mouse model, demonstrating promising treatment.

Язык: Английский

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Current pharmacological therapy for rheumatoid arthritis, factors for its effectiveness and associated complications: systematic review

Interdisciplinary Rehabilitation / Rehabilitacion Interdisciplinaria, Год журнала: 2024, Номер 4, С. 76 - 76

Опубликована: Янв. 11, 2024

Rheumatoid arthritis (RA) is a chronic, autoimmune, and systemic inflammatory disease that mainly affects diarthrodial joints. Its global prevalence 0,5-1 % in adults, increasing to 5 women over 55 years old. RA reduces the quality of life expectancy by 3-10 years, due associated cardiovascular diseases. Current treatment based on initiating early disease-modifying therapy with goal suppressing inflammation, inducing remission, preventing joint damage, improving functionality. Antirheumatic medications include non-steroidal anti-inflammatory drugs, glucocorticoids, non-biological immunosuppressants like methotrexate, biological immunomodulators such as anti-TNF or anti-interleukins, which have shown high clinical effectiveness. However, there individual variability therapeutic response, adverse effects, loss efficacy time. This study conducted systematic literature review following PRISMA methodology. The search was performed PubMed, Scopus, Web Science, using MESH terms keywords related rheumatoid arthritis, treatments, effectiveness, prognostic factors. Studies published between 2015-2022 were included, ultimately selecting 30 articles met eligibility criteria. objective this compile synthesize available evidence currently used therapies for factors success, most frequently reported complications effects. results contribute enhancing strategies, considering personalized approach each patient's needs.

Язык: Английский

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Development of biomedical hydrogels for rheumatoid arthritis treatment

Asian Journal of Pharmaceutical Sciences, Год журнала: 2024, Номер 19(1), С. 100887 - 100887

Опубликована: Фев. 1, 2024

Rheumatoid Arthritis (RA) is an autoimmune disorder that hinders the normal functioning of bones and joints reduces quality human life. Every year millions people are diagnosed with RA worldwide which particularly includes elderly women groups. Therefore, this global cause warrants development new biomaterials, medicines, therapeutic methods for treatment. This will improve Healthcare Access Quality Index also relieve administrative financial burdens healthcare service providers at a scale. Hydrogels soft cross-linked polymeric materials can store certain number fluids, drugs biomolecules hydration applications. biocompatible exhibit excellent mechanical properties like providing elastic cushions to articulating by mimicking natural synovial fluid. Hence, hydrogels create biological environment within cavity decrease reactions friction. lubricate joint surfaces prevent degradation cartilage, thus conceiting high potential treat RA. work reviews progress in injectable implantable hydrogels, synthesis methods, types drugs, advantages challenges, discusses role targeted drug delivery, mechanistic behaviour, tribological performance

Язык: Английский

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Roles and mechanisms of copper homeostasis and cuproptosis in osteoarticular diseases

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 174, С. 116570 - 116570

Опубликована: Апрель 9, 2024

Copper is an essential trace element in the human body that extensively distributed throughout various tissues. The appropriate level of copper crucial to maintaining life activities body, and excess deficiency can lead diseases. levels are regulated by homeostasis, which maintains tissues cells controlling its absorption, transport, storage. Cuproptosis a distinct form cell death induced excessive accumulation intracellular copper. homeostasis cuproptosis has recently elicited increased attention realm health. emerged as promising avenue for cancer therapy. Studies concerning osteoarticular diseases have elucidated intricate interplay among cuproptosis, onset dysregulation cause abnormal bone cartilage metabolism, affecting related cells. This phenomenon assumes critical role pathophysiological processes underpinning diseases, with implications inflammatory immune responses. While early Cu-modulating agents shown promise clinical settings, additional research advancements warranted enhance their efficacy. In this review, we summarize effects potential mechanisms on cartilage, well regulatory roles pathological mechanism (e.g., osteosarcoma (OS), osteoarthritis (OA), rheumatoid arthritis (RA)). We also discuss clinical-application prospects copper-targeting strategy, may provide new ideas diagnosis treatment

Язык: Английский

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Small molecule α-methylene-γ-butyrolactone, an evolutionarily conserved moiety in sesquiterpene lactones, ameliorates arthritic phenotype via interference DNA binding activity of NF-κB

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(8), С. 3561 - 3575

Опубликована: Апрель 8, 2024

Rheumatoid arthritis (RA) is an inflammatory disease accompanied by abnormal synovial microenvironment (SM). Sesquiterpene lactones (SLs) are the main anti-inflammatory ingredients of many traditional herbs utilized in RA treatment.

Язык: Английский

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