Development and evaluation of a protease inhibitor antiretroviral drug-loaded carbon nanotube delivery system for enhanced efficacy in HIV treatment
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved..
The primary objective of this study was to enhance the effectiveness of the protease inhibitor antiretroviral drug by designing a novel delivery system using carboxylated multiwalled carbon nanotubes (COOH-MWCNTs). To achieve this, Fosamprenavir calcium (FPV), a prodrug of amprenavir known for inhibiting the proteolytic cleavage of immature virions, was selected as the protease inhibitor antiretroviral drug, and loaded onto COOH-MWCNTs using a direct loading method. The structural specificity of the drug-loaded MWCNTs, the percent entrapment efficiency, and in vitro drug release were rigorously evaluated for the developed formulation, referred to as FPV-MWCNT. Fourier transform infrared (FTIR) spectroscopy, Field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, and atomic force microscopy (AFM) techniques were employed to confirm the structural integrity and specificity of the FPV-MWCNT formulation. The results demonstrated a remarkable entrapment efficiency of 79.57 ± 0.4 %, indicating the successful loading of FPV onto COOH-MWCNTs. FE-SEM and AFM analyses further confirmed the well-dispersed and elongated structure of the FPV-MWCNT formulation, without any signs of fracture, ensuring the stability and integrity of the drug delivery system. Moreover, particle size analysis revealed an average size of 290.1 nm, firmly establishing the nanoscale range of the formulation, with a zeta potential of 0.230 mV, signifying the system's colloidal stability. In vitro drug release studies conducted in methanolic phosphate buffer saline (PBS) at pH 7.4 and methanolic acetate buffer at pH 5 demonstrated sustained drug release from the FPV-MWCNT formulation. Over a period of 96 h, the formulation exhibited a cumulative drug release of 91.43 ± 2.3 %, showcasing the controlled and sustained release profile. Furthermore, hemolysis studies indicated a notable reduction in the toxicity of both FPV and MWCNT upon conjugation, although the percent hemolysis increased with higher concentrations, suggesting the need for careful consideration of dosage levels. In conclusion, the findings from this study underscore the potential of the FPV-MWCNT formulation as an effective and promising drug-conjugated system for delivering antiretroviral drugs. The successful encapsulation, sustained drug release, and reduced toxicity make FPV-MWCNT a compelling candidate for enhancing the therapeutic efficacy of protease inhibitor antiretroviral drugs in the treatment of HIV. The developed delivery system holds great promise for future advancements in HIV treatment and paves the way for further research and development in the field of drug delivery utilizing carbon nanotube-based systems.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:650 |
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| Enthalten in: |
International journal of pharmaceutics - 650(2024) vom: 25. Jan., Seite 123678 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Srivastava, Neha [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Infective Agents |
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| Anmerkungen: |
Date Completed 08.01.2024 Date Revised 08.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijpharm.2023.123678 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM365561789 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a The primary objective of this study was to enhance the effectiveness of the protease inhibitor antiretroviral drug by designing a novel delivery system using carboxylated multiwalled carbon nanotubes (COOH-MWCNTs). To achieve this, Fosamprenavir calcium (FPV), a prodrug of amprenavir known for inhibiting the proteolytic cleavage of immature virions, was selected as the protease inhibitor antiretroviral drug, and loaded onto COOH-MWCNTs using a direct loading method. The structural specificity of the drug-loaded MWCNTs, the percent entrapment efficiency, and in vitro drug release were rigorously evaluated for the developed formulation, referred to as FPV-MWCNT. Fourier transform infrared (FTIR) spectroscopy, Field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, and atomic force microscopy (AFM) techniques were employed to confirm the structural integrity and specificity of the FPV-MWCNT formulation. The results demonstrated a remarkable entrapment efficiency of 79.57 ± 0.4 %, indicating the successful loading of FPV onto COOH-MWCNTs. FE-SEM and AFM analyses further confirmed the well-dispersed and elongated structure of the FPV-MWCNT formulation, without any signs of fracture, ensuring the stability and integrity of the drug delivery system. Moreover, particle size analysis revealed an average size of 290.1 nm, firmly establishing the nanoscale range of the formulation, with a zeta potential of 0.230 mV, signifying the system's colloidal stability. In vitro drug release studies conducted in methanolic phosphate buffer saline (PBS) at pH 7.4 and methanolic acetate buffer at pH 5 demonstrated sustained drug release from the FPV-MWCNT formulation. Over a period of 96 h, the formulation exhibited a cumulative drug release of 91.43 ± 2.3 %, showcasing the controlled and sustained release profile. Furthermore, hemolysis studies indicated a notable reduction in the toxicity of both FPV and MWCNT upon conjugation, although the percent hemolysis increased with higher concentrations, suggesting the need for careful consideration of dosage levels. In conclusion, the findings from this study underscore the potential of the FPV-MWCNT formulation as an effective and promising drug-conjugated system for delivering antiretroviral drugs. The successful encapsulation, sustained drug release, and reduced toxicity make FPV-MWCNT a compelling candidate for enhancing the therapeutic efficacy of protease inhibitor antiretroviral drugs in the treatment of HIV. The developed delivery system holds great promise for future advancements in HIV treatment and paves the way for further research and development in the field of drug delivery utilizing carbon nanotube-based systems | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Anti-retroviral | |
| 650 | 4 | |a Disease | |
| 650 | 4 | |a Drug delivery | |
| 650 | 4 | |a Fosamprenavir | |
| 650 | 4 | |a HIV | |
| 650 | 4 | |a Multiwalled carbon nanotubes | |
| 650 | 7 | |a Nanotubes, Carbon |2 NLM | |
| 650 | 7 | |a Protease Inhibitors |2 NLM | |
| 650 | 7 | |a Enzyme Inhibitors |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Anti-Infective Agents |2 NLM | |
| 700 | 1 | |a Mishra, Vijay |e verfasserin |4 aut | |
| 700 | 1 | |a Mishra, Yachana |e verfasserin |4 aut | |
| 700 | 1 | |a Ranjan, Abhigyan |e verfasserin |4 aut | |
| 700 | 1 | |a Aljabali, Alaa A A |e verfasserin |4 aut | |
| 700 | 1 | |a El-Tanani, Mohamed |e verfasserin |4 aut | |
| 700 | 1 | |a Alfagih, Iman M |e verfasserin |4 aut | |
| 700 | 1 | |a Tambuwala, Murtaza M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of pharmaceutics |d 1992 |g 650(2024) vom: 25. Jan., Seite 123678 |w (DE-627)NLM07779785X |x 1873-3476 |7 nnns |
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