Fabrication of TPGS decorated Etravirine loaded lipidic nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targeting
Abstract 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 nanocarrier...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2024-01-01
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| Series: | Discover Nano |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11671-023-03954-x |
| _version_ | 1797362932297760768 |
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| author | Abdul Muheem Mohd. Wasim Eman Aldosari Sanjula Baboota Javed Ali |
| author_facet | Abdul Muheem Mohd. Wasim Eman Aldosari Sanjula Baboota Javed Ali |
| author_sort | Abdul Muheem |
| collection | DOAJ |
| description | Abstract 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. Graphical abstract |
| first_indexed | 2024-03-08T16:14:31Z |
| format | Article |
| id | doaj.art-921a0b8528104bc8856bce9920c94eef |
| institution | Directory Open Access Journal |
| issn | 2731-9229 |
| language | English |
| last_indexed | 2024-03-08T16:14:31Z |
| publishDate | 2024-01-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Nano |
| spelling | doaj.art-921a0b8528104bc8856bce9920c94eef2024-01-07T12:41:07ZengSpringerDiscover Nano2731-92292024-01-0119112710.1186/s11671-023-03954-xFabrication of TPGS decorated Etravirine loaded lipidic nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targetingAbdul Muheem0Mohd. Wasim1Eman Aldosari2Sanjula Baboota3Javed Ali4Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia HamdardDepartment of Pharmacology, School of Pharmaceutical Education and Research, Jamia HamdardDepartment of Chemistry, College of Science, King Saud UniversityDepartment of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia HamdardDepartment of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia HamdardAbstract 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. Graphical abstracthttps://doi.org/10.1186/s11671-023-03954-xLipidic nanocarriersNLCsTPGSEtravirineHIVAIDS |
| spellingShingle | Abdul Muheem Mohd. Wasim Eman Aldosari Sanjula Baboota Javed Ali Fabrication of TPGS decorated Etravirine loaded lipidic nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targeting Discover Nano Lipidic nanocarriers NLCs TPGS Etravirine HIV AIDS |
| title | Fabrication of TPGS decorated Etravirine loaded lipidic nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targeting |
| title_full | Fabrication of TPGS decorated Etravirine loaded lipidic nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targeting |
| title_fullStr | Fabrication of TPGS decorated Etravirine loaded lipidic nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targeting |
| title_full_unstemmed | Fabrication of TPGS decorated Etravirine loaded lipidic nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targeting |
| title_short | Fabrication of TPGS decorated Etravirine loaded lipidic nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targeting |
| title_sort | fabrication of tpgs decorated etravirine loaded lipidic nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targeting |
| topic | Lipidic nanocarriers NLCs TPGS Etravirine HIV AIDS |
| url | https://doi.org/10.1186/s11671-023-03954-x |
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