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Heath
Alternative Medicine
Novel treatment for refractory rheumatoid arthritis with total glucosides of paeony and nobiletin codelivered in a self-nanoemulsifying drug delivery
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<blockquote data-quote="greenmedinfo" data-source="post: 4899"><p>PMID: Acta Pharmacol Sin. 2021 Dec 6. Epub 2021 Dec 6. PMID: 34873316 Abstract Title: Novel treatment for refractory rheumatoid arthritis with total glucosides of paeony and nobiletin codelivered in a self-nanoemulsifying drug delivery system. Abstract: Patients with refractory rheumatoid arthritis (RA) remain a substantial clinical problem, while the overexpression of P-glycoprotein (P-gp) on their lymphocytes may contribute to resistance to anti-rheumatic drugs. This study aims to develop a novel treatment for refractory RA consisting of the combination of total glucosides of paeony (TGPs) and the P-gp inhibitor nobiletin (N), which are codelivered in a self-nanoemulsifying drug delivery system (SNEDDS). Based on the solubility, compatibility, and pseudoternary phase diagram tests, a nano-SNEDDS formulation composed of capryol 90-cremophor EL35-tcranscutol HP (CET) to codeliver TGP and N was developed, and this formulation increased the bioavailability of TGP by 435.04% (indicated with paeoniflorin). A modified adjuvant-induced arthritis (AIA) rat model was verified for the overexpression of P-gp in lymphocytes and resistance to methotrexate (MTX) treatment at the reported anti-inflammatory dosage. CET formulation not only increased the solubility and permeability of TGP but also inhibited the function and expression of P-gp, leading to enhanced bioavailability and intracellular concentration in the lymphocytes of AIA rats and consequently boosting the anti-arthritic effects of TGP. Moreover, TGP and N coloaded CET reduced the expression of P-gp in AIA rats partly by inhibiting the phosphorylated AKT and HIF-1α pathways. In summary, TGP-N coloaded SNEDDS is a novel and effective treatment for refractory RA. </p><p><a href="https://www.greenmedinfo.com/article/novel-treatment-refractory-rheumatoid-arthritis-total-glucosides-paeony-and-no" target="_blank">read more</a></p></blockquote><p></p>
[QUOTE="greenmedinfo, post: 4899"] PMID: Acta Pharmacol Sin. 2021 Dec 6. Epub 2021 Dec 6. PMID: 34873316 Abstract Title: Novel treatment for refractory rheumatoid arthritis with total glucosides of paeony and nobiletin codelivered in a self-nanoemulsifying drug delivery system. Abstract: Patients with refractory rheumatoid arthritis (RA) remain a substantial clinical problem, while the overexpression of P-glycoprotein (P-gp) on their lymphocytes may contribute to resistance to anti-rheumatic drugs. This study aims to develop a novel treatment for refractory RA consisting of the combination of total glucosides of paeony (TGPs) and the P-gp inhibitor nobiletin (N), which are codelivered in a self-nanoemulsifying drug delivery system (SNEDDS). Based on the solubility, compatibility, and pseudoternary phase diagram tests, a nano-SNEDDS formulation composed of capryol 90-cremophor EL35-tcranscutol HP (CET) to codeliver TGP and N was developed, and this formulation increased the bioavailability of TGP by 435.04% (indicated with paeoniflorin). A modified adjuvant-induced arthritis (AIA) rat model was verified for the overexpression of P-gp in lymphocytes and resistance to methotrexate (MTX) treatment at the reported anti-inflammatory dosage. CET formulation not only increased the solubility and permeability of TGP but also inhibited the function and expression of P-gp, leading to enhanced bioavailability and intracellular concentration in the lymphocytes of AIA rats and consequently boosting the anti-arthritic effects of TGP. Moreover, TGP and N coloaded CET reduced the expression of P-gp in AIA rats partly by inhibiting the phosphorylated AKT and HIF-1α pathways. In summary, TGP-N coloaded SNEDDS is a novel and effective treatment for refractory RA. [URL='https://www.greenmedinfo.com/article/novel-treatment-refractory-rheumatoid-arthritis-total-glucosides-paeony-and-no']read more[/URL] [/QUOTE]
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Novel treatment for refractory rheumatoid arthritis with total glucosides of paeony and nobiletin codelivered in a self-nanoemulsifying drug delivery
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