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- W2949156773 endingPage "118447" @default.
- W2949156773 startingPage "118447" @default.
- W2949156773 abstract "Oral treatment of rheumatoid arthritis (RA) with the immunomodulator, leflunomide (LEF), is associated with systemic side effects namely immunosuppression and hepatotoxicity. Herein, attempts to improve LEF therapeutic outcomes via nanostructured lipid carriers (NLCs) targeting inflamed rheumatic joints were executed. LEF-NLCs coated with either chondroitin sulphate (CHS) or chitosan (CS) were around 250 nm in size with negative or positive charge, respectively. Particle coating was evidenced by TEM and FTIR analysis. NLCs generally ensured sustained release profile up to 21 days, particularly extended in coated formulations. In vivo pharmacokinetic study of LEF suspension, uncoated NLCs, CHS- and CS-coated NLCs was carried out. Following oral administration in RA-induced rat model, joint diameter, paw inflammation, liver functions were measured, in addition to histological examination of liver, kidney and joints. Results revealed improved joint healing and reduced hepatotoxicity following treatment with nanoencapsulated LEF compared to LEF suspension, whereby CHS-NLCs ensued the highest Cmax, AUC and lowest TNF-α level. The dual potential of CHS to achieve active targeting to CD44-receptor and hence maximize LEF concentration at the target site in addition to its synergistic effect in joint healing endow promises for a competent oral nanosystem for targeted drug delivery to the joints." @default.
- W2949156773 created "2019-06-27" @default.
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- W2949156773 date "2019-08-01" @default.
- W2949156773 modified "2023-10-09" @default.
- W2949156773 title "Coated nanostructured lipid carriers targeting the joints – An effective and safe approach for the oral management of rheumatoid arthritis" @default.
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- W2949156773 doi "https://doi.org/10.1016/j.ijpharm.2019.118447" @default.
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