Sirolimus loaded chitosan functionalized poly (lactic-co-glycolic acid) (PLGA) nanoparticles for potential treatment of age-related macular degeneration
Copyright © 2021 Elsevier B.V. All rights reserved..
The usefulness of sirolimus (SIR) in the treatment of diseases that involve retinal degeneration like age-related macular degeneration (AMD) has been well documented. However, the problem still remains probably owing to the peculiar environment of the eye and/or unfavourable physiochemical profile of SIR. In the present work, we aimed to fabricate sirolimus loaded PLGA nanoparticles (SIR-PLGA-NP) and chitosan decorated PLGA nanoparticles (SIR-CH-PLGA-NP) to be administered via non-invasive subconjunctival route. Both the nanoparticles were characterized in terms of size, zeta potential, DSC, FTIR and XRD analysis. Quality by Design (QbD) approach was employed during the preparation of nanoparticles and the presence of chitosan coating was confirmed through thermogravimetric analysis and contact angle studies. Cationic polymer modification showed sustained in-vitro SIR release and enhanced ex-vivo scleral permeation and penetration. Further, SIR-CH-PLGA-NP revealed enhanced cellular uptake and thus, reduced lipopolysaccharide (LPS)-induced free-radicals generation by RAW 264.7 cells. The prepared nanoparticles were devoid of residual solvent and were found to be safe in HET-CAM analysis, RBCs damage analysis and histopathology studies. Moreover, high anti-angiogenic potential was observed in SIR-CH-PLGA-NP compared with SIR-PLGA-NP in chorioallantoic membrane (CAM) test. Overall, the current work opens up an avenue for further investigation of CH-PLGA-NP as SIR nanocarrier in the treatment of AMD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:191 |
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| Enthalten in: |
International journal of biological macromolecules - 191(2021) vom: 30. Nov., Seite 548-559 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Suri, Reshal [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.12.2021 Date Revised 15.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijbiomac.2021.09.069 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM330784056 |
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| 520 | |a Copyright © 2021 Elsevier B.V. All rights reserved. | ||
| 520 | |a The usefulness of sirolimus (SIR) in the treatment of diseases that involve retinal degeneration like age-related macular degeneration (AMD) has been well documented. However, the problem still remains probably owing to the peculiar environment of the eye and/or unfavourable physiochemical profile of SIR. In the present work, we aimed to fabricate sirolimus loaded PLGA nanoparticles (SIR-PLGA-NP) and chitosan decorated PLGA nanoparticles (SIR-CH-PLGA-NP) to be administered via non-invasive subconjunctival route. Both the nanoparticles were characterized in terms of size, zeta potential, DSC, FTIR and XRD analysis. Quality by Design (QbD) approach was employed during the preparation of nanoparticles and the presence of chitosan coating was confirmed through thermogravimetric analysis and contact angle studies. Cationic polymer modification showed sustained in-vitro SIR release and enhanced ex-vivo scleral permeation and penetration. Further, SIR-CH-PLGA-NP revealed enhanced cellular uptake and thus, reduced lipopolysaccharide (LPS)-induced free-radicals generation by RAW 264.7 cells. The prepared nanoparticles were devoid of residual solvent and were found to be safe in HET-CAM analysis, RBCs damage analysis and histopathology studies. Moreover, high anti-angiogenic potential was observed in SIR-CH-PLGA-NP compared with SIR-PLGA-NP in chorioallantoic membrane (CAM) test. Overall, the current work opens up an avenue for further investigation of CH-PLGA-NP as SIR nanocarrier in the treatment of AMD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Age-related macular degeneration (AMD) | |
| 650 | 4 | |a Box-Behnken Design | |
| 650 | 4 | |a Chitosan | |
| 650 | 4 | |a Chorioallantoic membrane (CAM) | |
| 650 | 4 | |a PLGA | |
| 650 | 4 | |a Raw 264.7 cells | |
| 650 | 4 | |a Sirolimus | |
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| 700 | 1 | |a Neupane, Yub Raj |e verfasserin |4 aut | |
| 700 | 1 | |a Mehra, Nikita |e verfasserin |4 aut | |
| 700 | 1 | |a Nematullah, Md |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Farah |e verfasserin |4 aut | |
| 700 | 1 | |a Alam, Ozair |e verfasserin |4 aut | |
| 700 | 1 | |a Iqubal, Ashif |e verfasserin |4 aut | |
| 700 | 1 | |a Jain, Gaurav Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Kohli, Kanchan |e verfasserin |4 aut | |
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