Sinapic acid-pullulan based inflammation responsive nanomicelles for the local treatment of experimental inflammatory arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints. It is one of the major causes of disability and morbidity worldwide. Administration of conventional drugs through the systemic route restricts the bioavailability of drugs, systemic toxicity, and reduced efficacy. We have introd...

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Bibliographic Details
Published in:International journal of biological macromolecules 2024-10, Vol.278 (Pt 3), p.134903, Article 134903
Main Authors: Ali, Aneesh, Rahul, Jori, Chandrashekhar, Kumar, Jattin, Kumar, Ajay, Kanika, Ansari, Md. Meraj, Ahmad, Anas, Ali, Nemat, Yadav, Poonam, Parvez, Suhel, Navik, Umashanker, Son, Young-Ok, Khan, Rehan
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - chemistry
Anti-Inflammatory Agents - pharmacology
Anti-Inflammatory Agents - therapeutic use
Arthritis, Experimental - drug therapy
Arthritis, Experimental - pathology
Coumaric Acids - chemistry
Coumaric Acids - pharmacology
Drug Carriers - chemistry
Glucans - chemistry
Glucans - pharmacology
Inflammation
Inflammation - drug therapy
Male
Mice
Nanoparticles - chemistry
Pullulan
Rats
Rheumatoid arthritis
Sinapic acid
Stimuli-responsive
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Summary:Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints. It is one of the major causes of disability and morbidity worldwide. Administration of conventional drugs through the systemic route restricts the bioavailability of drugs, systemic toxicity, and reduced efficacy. We have introduced Rebamipide (Reb)-loaded Sinapic acid (SA)-Pullulan (PL) nanomicelles (Reb@SA-PL NMs), a nanotechnology based drug delivery system for the treatment of inflammatory arthritis. PL is a polysaccharide obtained from the fungus Aureobasidium pullulans, and SA is a bioactive polyphenol found in various plants. Both are classified by US-FDA Generally Recognised as Safe (GRAS) materials. Reb@SA-PL NMs found to be cytocompatible. Subsequently, intra-articular administration of Reb@SA-PL NMs enhances the anti-arthritic potential compared to free Reb drug in collagen-induced experimental inflammatory arthritis rat model. Reb@SA-PL NMs reduced the expression of RANKL receptor and Nf-κB. Reb@SA-PL NMs reverses the breakdown of type II collagen, MMP-13, and inhibits the pro-inflammatory markers. Reb@SA-PL NMs prevented bone erosion, cartilage degradation, joint oedema, and synovial inflammation. The results of the study demonstrated that Reb@SA-PL NMs, an enzyme-responsive drug delivery system, has excellent potential for alleviating inflammatory arthritis by blocking MMP-13 and RANKL.
ISSN:0141-8130
1879-0003
1879-0003
DOI:10.1016/j.ijbiomac.2024.134903