Hyaluronic acid-coated proglycosomes for topical delivery of tofacitinib in rheumatoid arthritis condition : Formulation design, in vitro, ex vivo characterization, and in vivo efficacy studies
Copyright © 2022 Elsevier B.V. All rights reserved..
Tofacitinib (TF) is a selective oral jakanib approved by the USFDA for the treatment of rheumatoid arthritis (RA). To overcome the adverse effects of orally administered TF, topical delivery can be a suitable choice. The therapeutic efficacy of TF can be improved through the high affinity of natural ligands (hyaluronic acid and chondroitin sulphate) to CD44 receptors on the macrophages or other immune cells in the dermal region. Thus, the present research work was inspired by the possibility to develop and evaluate the potential of hyaluronic acid-coated proglycosomes (HA-TF-PG) as the carrier for site-specific dermal delivery. The normal-PG (N-TF-PG) and HA-TF-PG showed particle sizes of <250 nm. The HA-TF-PG demonstrated 3.15-fold higher retention of TF in the viable dermis layers than the conventional formulation. The in vivo pharmacodynamic study, cytokines, and radiographic study on Complete Freud's Adjuvant-induced arthritic rat model revealed that HA-TF-PG exhibited a significant (P < 0.001) reduction in inflammation in arthritic rat's paw compared to the conventional TF. The developed HA-TF-PG treated groups showed significantly lowered CD44 levels compared to FD-gel and N-TF-PG i.e. 2.28 and 1.32-fold respectively (p < 0.001). In conclusion, The HA-TF-PG can be developed as an effective carrier for the site-specific dermal drug delivery system of TF to treat RA.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:224 |
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| Enthalten in: |
International journal of biological macromolecules - 224(2023) vom: 01. Jan., Seite 207-222 |
| 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 21.12.2022 Date Revised 22.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijbiomac.2022.10.117 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM347881475 |
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| 520 | |a Copyright © 2022 Elsevier B.V. All rights reserved. | ||
| 520 | |a Tofacitinib (TF) is a selective oral jakanib approved by the USFDA for the treatment of rheumatoid arthritis (RA). To overcome the adverse effects of orally administered TF, topical delivery can be a suitable choice. The therapeutic efficacy of TF can be improved through the high affinity of natural ligands (hyaluronic acid and chondroitin sulphate) to CD44 receptors on the macrophages or other immune cells in the dermal region. Thus, the present research work was inspired by the possibility to develop and evaluate the potential of hyaluronic acid-coated proglycosomes (HA-TF-PG) as the carrier for site-specific dermal delivery. The normal-PG (N-TF-PG) and HA-TF-PG showed particle sizes of <250 nm. The HA-TF-PG demonstrated 3.15-fold higher retention of TF in the viable dermis layers than the conventional formulation. The in vivo pharmacodynamic study, cytokines, and radiographic study on Complete Freud's Adjuvant-induced arthritic rat model revealed that HA-TF-PG exhibited a significant (P < 0.001) reduction in inflammation in arthritic rat's paw compared to the conventional TF. The developed HA-TF-PG treated groups showed significantly lowered CD44 levels compared to FD-gel and N-TF-PG i.e. 2.28 and 1.32-fold respectively (p < 0.001). In conclusion, The HA-TF-PG can be developed as an effective carrier for the site-specific dermal drug delivery system of TF to treat RA | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CD44 | |
| 650 | 4 | |a Hyaluronic acid-coated proglycosomes | |
| 650 | 4 | |a Rheumatoid arthritis | |
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| 700 | 1 | |a Singhvi, Gautam |e verfasserin |4 aut | |
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