Self-assembled sodium alginate polymannuronate nanoparticles for synergistic treatment of ophthalmic infection and inflammation : Preparation optimization and in vitro/vivo evaluation
Copyright © 2024 Elsevier B.V. All rights reserved..
Frequent administrations are often needed during the treatment of ocular diseases due to the low bioavailability of the existing eye drops owing to inadequate corneal penetration and rapid drug washout. Herein, sodium alginate polymannuronate (SA) nanocarriers were developed using ionic gelation method that can provide better bioavailability through mucoadhesivity and sustained drug release by binding to the ocular mucus layer. This study disproves the common belief that only the G block of SA participates in the crosslinking reaction during ionic gelation. Self-assembly capability due to the linear flexible structure of the M block, better biocompatibility than G block along with the feasibility of controlling physicochemical characteristics postulate a high potential for designing efficient ocular drug delivery systems. Initially, four crosslinkers of varied concentrations were investigated. Taguchi design of experiment revealed the statistically significant effect of the crosslinker type and concentration on the particle size and stability. The best combination was detected by analyzing the particle size and zeta potential values that showed the desired microstructural properties for ocular barrier penetration. The desired combination was SA-Ca-1 that had particle size within the optimal corneal penetration range, that is 10-200 nm (135 nm). The drug carriers demonstrated excellent entrapment efficiency (∼89 % for Ciprofloxacin and ∼96 % for Dexamethasone) along with a sustained and simultaneous release of dual drug for at least 2 days. The nanoparticles also showed biocompatibility (4 ± 0.6 % hemolysis) and high mucoadhesivity (73 ± 2 % for 0.25 g) which was validated by molecular docking analysis. The prepared formulation was able to reduce the scleral inflammation of the rabbit uveitis models significantly within 3 days. Thus, the eye drop showed remarkable potential for efficient drug delivery leading to faster recovery.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:262 |
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| Enthalten in: |
International journal of biological macromolecules - 262(2024), Pt 2 vom: 25. März, Seite 130038 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Datta, Nondita [VerfasserIn] |
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| Links: |
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| Themen: |
9012-76-4 |
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| Anmerkungen: |
Date Completed 27.03.2024 Date Revised 27.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijbiomac.2024.130038 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a Frequent administrations are often needed during the treatment of ocular diseases due to the low bioavailability of the existing eye drops owing to inadequate corneal penetration and rapid drug washout. Herein, sodium alginate polymannuronate (SA) nanocarriers were developed using ionic gelation method that can provide better bioavailability through mucoadhesivity and sustained drug release by binding to the ocular mucus layer. This study disproves the common belief that only the G block of SA participates in the crosslinking reaction during ionic gelation. Self-assembly capability due to the linear flexible structure of the M block, better biocompatibility than G block along with the feasibility of controlling physicochemical characteristics postulate a high potential for designing efficient ocular drug delivery systems. Initially, four crosslinkers of varied concentrations were investigated. Taguchi design of experiment revealed the statistically significant effect of the crosslinker type and concentration on the particle size and stability. The best combination was detected by analyzing the particle size and zeta potential values that showed the desired microstructural properties for ocular barrier penetration. The desired combination was SA-Ca-1 that had particle size within the optimal corneal penetration range, that is 10-200 nm (135 nm). The drug carriers demonstrated excellent entrapment efficiency (∼89 % for Ciprofloxacin and ∼96 % for Dexamethasone) along with a sustained and simultaneous release of dual drug for at least 2 days. The nanoparticles also showed biocompatibility (4 ± 0.6 % hemolysis) and high mucoadhesivity (73 ± 2 % for 0.25 g) which was validated by molecular docking analysis. The prepared formulation was able to reduce the scleral inflammation of the rabbit uveitis models significantly within 3 days. Thus, the eye drop showed remarkable potential for efficient drug delivery leading to faster recovery | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Dual drug delivery | |
| 650 | 4 | |a Ionic crosslinking | |
| 650 | 4 | |a Nanoparticle | |
| 650 | 4 | |a Sodium alginate | |
| 650 | 7 | |a Alginates |2 NLM | |
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| 700 | 1 | |a Wong, Siew Yee |e verfasserin |4 aut | |
| 700 | 1 | |a Chakravarty, Saumitra |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xu |e verfasserin |4 aut | |
| 700 | 1 | |a Anwar, Ishtiaque |e verfasserin |4 aut | |
| 700 | 1 | |a Arafat, M Tarik |e verfasserin |4 aut | |
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