Pazopanib-laden lipid based nanovesicular delivery with augmented oral bioavailability and therapeutic efficacy against non-small cell lung cancer
Copyright © 2022 Elsevier B.V. All rights reserved..
The present investigation deals with the pazopanib-loaded solid lipid nanoparticles (Pazo-SLNs) and their in-vitro and in-vivo assessments. Quality by design approach employing the Plackett-Burman and central composite design was used to identify the formulation variables, including drug/lipid ratio, organic/aqueous phase ratio, and surfactant concentration with a significant impact on the process and to fabricate a safe and efficacious novel oral dosage form of pazopanib. Particle size, drug loading, entrapment efficiency, and zeta potential of optimal Pazo-SLNs formulation were 210.03 ± 7.68 nm, 13.35 ± 0.95 %, 79.05 ± 2.55 % and -18.29 ± 1.89 mV (n = 3) respectively. FTIR study affirmed the absence of incompatibilities between the drug and the excipients. DSC and XRD measurements substantiated the amorphous form of pazopanib entrapped within the SLNs. Pazo-SLNs demonstrated high cellular uptake, showed substantial cytotoxicity to A-549 lung cancer cells due to apoptotic mode and inhibited tyrosine kinase in-vitro. Pazo-SLNs were found to be stable for three months. SLNs greatly ameliorated the pharmacokinetic behavior and bioavailability (9.5 folds) of pazopanib with a sustained-release pattern (92.67 ± 4.68 % within 24 h). A biodistribution study corroborated the lung targeting potential of Pazo-SLNs. Thus, SLNs could potentially boost the oral route efficacy of pazopanib against cancer cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:628 |
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| Enthalten in: |
International journal of pharmaceutics - 628(2022) vom: 25. Nov., Seite 122287 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nadaf, Sameer J [VerfasserIn] |
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| Links: |
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| Themen: |
7RN5DR86CK |
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| Anmerkungen: |
Date Completed 15.11.2022 Date Revised 15.11.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijpharm.2022.122287 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM347722326 |
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| 520 | |a Copyright © 2022 Elsevier B.V. All rights reserved. | ||
| 520 | |a The present investigation deals with the pazopanib-loaded solid lipid nanoparticles (Pazo-SLNs) and their in-vitro and in-vivo assessments. Quality by design approach employing the Plackett-Burman and central composite design was used to identify the formulation variables, including drug/lipid ratio, organic/aqueous phase ratio, and surfactant concentration with a significant impact on the process and to fabricate a safe and efficacious novel oral dosage form of pazopanib. Particle size, drug loading, entrapment efficiency, and zeta potential of optimal Pazo-SLNs formulation were 210.03 ± 7.68 nm, 13.35 ± 0.95 %, 79.05 ± 2.55 % and -18.29 ± 1.89 mV (n = 3) respectively. FTIR study affirmed the absence of incompatibilities between the drug and the excipients. DSC and XRD measurements substantiated the amorphous form of pazopanib entrapped within the SLNs. Pazo-SLNs demonstrated high cellular uptake, showed substantial cytotoxicity to A-549 lung cancer cells due to apoptotic mode and inhibited tyrosine kinase in-vitro. Pazo-SLNs were found to be stable for three months. SLNs greatly ameliorated the pharmacokinetic behavior and bioavailability (9.5 folds) of pazopanib with a sustained-release pattern (92.67 ± 4.68 % within 24 h). A biodistribution study corroborated the lung targeting potential of Pazo-SLNs. Thus, SLNs could potentially boost the oral route efficacy of pazopanib against cancer cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Central composite design | |
| 650 | 4 | |a Controlled release | |
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| 650 | 4 | |a Plackett-Burman design | |
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| 700 | 1 | |a Kumbar, Vijay M |e verfasserin |4 aut | |
| 700 | 1 | |a Bhagwat, Durgacharan A |e verfasserin |4 aut | |
| 700 | 1 | |a Gurav, Shailendra S |e verfasserin |4 aut | |
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