Fabrication of TPGS decorated Etravirine loaded lipidic nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targeting
© 2024. The Author(s)..
Etravirine (ERVN) is a potential NNRTI (non-nucleoside reverse transcriptase inhibitor) in treating HIV infection. It possesses extremely low oral bioavailability. The present research aims to optimize the formulation and characterization of TPGS-enriched ERVN-loaded lipid-based nanocarriers (NLCs) for HIV-infected patients. The formulation, ERVN-TPGS-NLCs, was optimized by central composite rotational design using a modified-solvent emulsification process. Various characterization parameters of NLCs were evaluated, including globule size of 121.56 ± 2.174 nm, PDI of 0.172 ± 0.042, the zeta potential of - 7.32 ± 0.021 mV, %EE of 94.42 ± 8.65% of ERVN and %DL was 8.94 ± 0.759% of ERVN and spherical shape was revealed by TEM. PXRD was also performed to identify the crystallinity of the sample. In-vitro drug release showed % a cumulative drug release of 83.72 ± 8.35% at pH 1.2 and 90.61 ± 9.11% at pH 6.8, respectively, whereas the % cumulative drug release from drug suspension (ERVN-S) was found to be 21.13 ± 2.01% at pH 1.2 and 24.84 ± 2.51 at pH 6.8 at the end of 48 h. Further, the intestinal permeation study and confocal microscope showed approximately three-fold and two-fold increased permeation in ERVN-TPGS-NLCs and ERVN-NLCs across the gut sac compared to ERVN-S. Hemolysis compatibility and lipolysis studies were performed to predict the in-vivo fate of the formulation. The pharmacokinetic study revealed a 3.13-fold increment in the relative bioavailability, which agrees with the ex-vivo studies, and lymphatic uptake was validated by using cycloheximide along with designed formulation, which showed the impact of lymphatic uptake in AUC. This study ensures that ERVN-TPGS-NLCs take lymphatic uptake to minimize the first-pass metabolism followed by improved oral bioavailability of ERVN. Thus, the enhanced bioavailability of ERVN can reduce the high dose of ERVN to minimize the adverse effects related to dose-related burden.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
Discover nano - 19(2024), 1 vom: 04. Jan., Seite 5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Muheem, Abdul [VerfasserIn] |
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| Links: |
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| Themen: |
AIDS |
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| Anmerkungen: |
Date Revised 08.01.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1186/s11671-023-03954-x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Etravirine (ERVN) is a potential NNRTI (non-nucleoside reverse transcriptase inhibitor) in treating HIV infection. It possesses extremely low oral bioavailability. The present research aims to optimize the formulation and characterization of TPGS-enriched ERVN-loaded lipid-based nanocarriers (NLCs) for HIV-infected patients. The formulation, ERVN-TPGS-NLCs, was optimized by central composite rotational design using a modified-solvent emulsification process. Various characterization parameters of NLCs were evaluated, including globule size of 121.56 ± 2.174 nm, PDI of 0.172 ± 0.042, the zeta potential of - 7.32 ± 0.021 mV, %EE of 94.42 ± 8.65% of ERVN and %DL was 8.94 ± 0.759% of ERVN and spherical shape was revealed by TEM. PXRD was also performed to identify the crystallinity of the sample. In-vitro drug release showed % a cumulative drug release of 83.72 ± 8.35% at pH 1.2 and 90.61 ± 9.11% at pH 6.8, respectively, whereas the % cumulative drug release from drug suspension (ERVN-S) was found to be 21.13 ± 2.01% at pH 1.2 and 24.84 ± 2.51 at pH 6.8 at the end of 48 h. Further, the intestinal permeation study and confocal microscope showed approximately three-fold and two-fold increased permeation in ERVN-TPGS-NLCs and ERVN-NLCs across the gut sac compared to ERVN-S. Hemolysis compatibility and lipolysis studies were performed to predict the in-vivo fate of the formulation. The pharmacokinetic study revealed a 3.13-fold increment in the relative bioavailability, which agrees with the ex-vivo studies, and lymphatic uptake was validated by using cycloheximide along with designed formulation, which showed the impact of lymphatic uptake in AUC. This study ensures that ERVN-TPGS-NLCs take lymphatic uptake to minimize the first-pass metabolism followed by improved oral bioavailability of ERVN. Thus, the enhanced bioavailability of ERVN can reduce the high dose of ERVN to minimize the adverse effects related to dose-related burden | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AIDS | |
| 650 | 4 | |a Bioavailability | |
| 650 | 4 | |a Etravirine | |
| 650 | 4 | |a HIV | |
| 650 | 4 | |a Lipidic nanocarriers | |
| 650 | 4 | |a Lymphatic uptake | |
| 650 | 4 | |a NLCs | |
| 650 | 4 | |a TPGS | |
| 700 | 1 | |a Wasim, Mohd |e verfasserin |4 aut | |
| 700 | 1 | |a Aldosari, Eman |e verfasserin |4 aut | |
| 700 | 1 | |a Baboota, Sanjula |e verfasserin |4 aut | |
| 700 | 1 | |a Ali, Javed |e verfasserin |4 aut | |
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