Design of chondroitin sulphate coated proglycosomes for localized delivery of tofacitinib for the treatment of rheumatoid arthritis
Copyright © 2023 Elsevier B.V. All rights reserved..
Long-term oral tofacitinib (TOF) administration has been linked to serious side effects majorly immunological suppression. The aim of this work was to enhance the therapeutic efficacy of TOF by chondroitin sulphate (CS) coated proglycosomes through the anchoring of high-affinity CS to CD44 receptors on immune cells in the inflammatory region. The CS was coated onto the TOF-loaded proglycosomes (CS-TOF-PG) formulations and they were evaluated for in vitro drug release, ex vivo (permeation, dermatokinetics) studies. In vivo efficacy studies were carried out in Freund's complete adjuvant (CFA) induced arthritis model. The optimized CS-TOF-PG showed particle sizes of 181.13 ± 7.21 nm with an entrapment efficiency of 78.85 ± 3.65 %. Ex-vivo studies of CS-TOF-PG gel exhibited 1.5-fold high flux and 1.4-fold dermal retention compared to FD-gel. The efficacy study revealed that CS-TOF-PG showed a significant (P < 0.001) reduction in inflammation in arthritic rat paws compared to the TOF oral and FD gel. The current study ensured that the CS-TOF-PG topical gel system would provide a safe and effective formulation for localization and site-specific delivery of TOF at the RA site and overcome the adverse effects associated with the TOF.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:186 |
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| Enthalten in: |
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V - 186(2023) vom: 01. Mai, Seite 43-54 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gorantla, Srividya [VerfasserIn] |
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| Links: |
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| Themen: |
87LA6FU830 |
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| Anmerkungen: |
Date Completed 25.04.2023 Date Revised 25.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejpb.2023.03.008 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354462490 |
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| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a Long-term oral tofacitinib (TOF) administration has been linked to serious side effects majorly immunological suppression. The aim of this work was to enhance the therapeutic efficacy of TOF by chondroitin sulphate (CS) coated proglycosomes through the anchoring of high-affinity CS to CD44 receptors on immune cells in the inflammatory region. The CS was coated onto the TOF-loaded proglycosomes (CS-TOF-PG) formulations and they were evaluated for in vitro drug release, ex vivo (permeation, dermatokinetics) studies. In vivo efficacy studies were carried out in Freund's complete adjuvant (CFA) induced arthritis model. The optimized CS-TOF-PG showed particle sizes of 181.13 ± 7.21 nm with an entrapment efficiency of 78.85 ± 3.65 %. Ex-vivo studies of CS-TOF-PG gel exhibited 1.5-fold high flux and 1.4-fold dermal retention compared to FD-gel. The efficacy study revealed that CS-TOF-PG showed a significant (P < 0.001) reduction in inflammation in arthritic rat paws compared to the TOF oral and FD gel. The current study ensured that the CS-TOF-PG topical gel system would provide a safe and effective formulation for localization and site-specific delivery of TOF at the RA site and overcome the adverse effects associated with the TOF | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CD44 | |
| 650 | 4 | |a Chondroitin sulphate | |
| 650 | 4 | |a Proglycosomes | |
| 650 | 4 | |a Rheumatoid arthritis | |
| 650 | 4 | |a Tofacitinib | |
| 650 | 7 | |a Chondroitin Sulfates |2 NLM | |
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| 650 | 7 | |a tofacitinib |2 NLM | |
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| 650 | 7 | |a Piperidines |2 NLM | |
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| 700 | 1 | |a Naidu, V G M |e verfasserin |4 aut | |
| 700 | 1 | |a Saha, Ranendra N |e verfasserin |4 aut | |
| 700 | 1 | |a Singhvi, Gautam |e verfasserin |4 aut | |
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