Cargando…

QbD Enabled Azacitidine Loaded Liposomal Nanoformulation and Its In Vitro Evaluation

Azacitidine (AZA), an inhibitor of DNA methyltransferase, is a commonly recognized drug used in clinical treatment for myelodysplastic syndrome and breast cancer. Due to higher aqueous solubility and negative log P of AZA causes poor cancer cell permeation and controlled release. The objective of th...

Descripción completa

Detalles Bibliográficos
Autores principales: Kesharwani, Prashant, Md, Shadab, Alhakamy, Nabil A., Hosny, Khaled M., Haque, Anzarul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828524/
https://www.ncbi.nlm.nih.gov/pubmed/33451016
http://dx.doi.org/10.3390/polym13020250
_version_ 1783641030111789056
author Kesharwani, Prashant
Md, Shadab
Alhakamy, Nabil A.
Hosny, Khaled M.
Haque, Anzarul
author_facet Kesharwani, Prashant
Md, Shadab
Alhakamy, Nabil A.
Hosny, Khaled M.
Haque, Anzarul
author_sort Kesharwani, Prashant
collection PubMed
description Azacitidine (AZA), an inhibitor of DNA methyltransferase, is a commonly recognized drug used in clinical treatment for myelodysplastic syndrome and breast cancer. Due to higher aqueous solubility and negative log P of AZA causes poor cancer cell permeation and controlled release. The objective of the present study was to formulate and optimize AZA-loaded liposome (AZA-LIPO) for breast cancer chemotherapy by using Box Behnken design (BBD) and in vitro evaluation using MCF-7 cells. AZA-LIPO were prepared using a thin film hydration technique and characterization study was performed by using FTIR and DSC. The prepared formulations were optimized using BBD and the optimized formulation was further subjected for particle size, surface charges, polydispersity index (PDI), drug loading, entrapment efficiency, TEM, XRD, in-vitro drug release and hemolytic toxicity. The mean particle size of optimized AZA-LIPO was 127 nm. Entrapment efficiency and drug loading of AZA-LIPO was found to be 85.2% ± 0.5 and 6.82 ± 1.6%, respectively. Further, in vitro drug release study showed preliminary burst release in 2 h followed by a sustained release for 36 h in phosphate buffer at different pH (4.0, 5.5, and 7.4) as compared to free drug. Drug release was found to be pH dependent, as the pH was increased, the drug release rate was found to be low. Time-dependent cell viability assay exhibited significant higher cell viability and higher internalization than free AZA in MCF-7 cells. AZA-LIPO were more effective than the free AZA in reducing Bcl2 expression, while increasing pro-apoptotic Bax and caspase-3 activity. The result showed that the formulated biocompatible AZA-LIPO nano-formulations may be used as an efficient anti-cancer drug delivery system for the treatment of breast cancer after establishing preclinical and clinical studies.
format Online
Article
Text
id pubmed-7828524
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-78285242021-01-25 QbD Enabled Azacitidine Loaded Liposomal Nanoformulation and Its In Vitro Evaluation Kesharwani, Prashant Md, Shadab Alhakamy, Nabil A. Hosny, Khaled M. Haque, Anzarul Polymers (Basel) Article Azacitidine (AZA), an inhibitor of DNA methyltransferase, is a commonly recognized drug used in clinical treatment for myelodysplastic syndrome and breast cancer. Due to higher aqueous solubility and negative log P of AZA causes poor cancer cell permeation and controlled release. The objective of the present study was to formulate and optimize AZA-loaded liposome (AZA-LIPO) for breast cancer chemotherapy by using Box Behnken design (BBD) and in vitro evaluation using MCF-7 cells. AZA-LIPO were prepared using a thin film hydration technique and characterization study was performed by using FTIR and DSC. The prepared formulations were optimized using BBD and the optimized formulation was further subjected for particle size, surface charges, polydispersity index (PDI), drug loading, entrapment efficiency, TEM, XRD, in-vitro drug release and hemolytic toxicity. The mean particle size of optimized AZA-LIPO was 127 nm. Entrapment efficiency and drug loading of AZA-LIPO was found to be 85.2% ± 0.5 and 6.82 ± 1.6%, respectively. Further, in vitro drug release study showed preliminary burst release in 2 h followed by a sustained release for 36 h in phosphate buffer at different pH (4.0, 5.5, and 7.4) as compared to free drug. Drug release was found to be pH dependent, as the pH was increased, the drug release rate was found to be low. Time-dependent cell viability assay exhibited significant higher cell viability and higher internalization than free AZA in MCF-7 cells. AZA-LIPO were more effective than the free AZA in reducing Bcl2 expression, while increasing pro-apoptotic Bax and caspase-3 activity. The result showed that the formulated biocompatible AZA-LIPO nano-formulations may be used as an efficient anti-cancer drug delivery system for the treatment of breast cancer after establishing preclinical and clinical studies. MDPI 2021-01-13 /pmc/articles/PMC7828524/ /pubmed/33451016 http://dx.doi.org/10.3390/polym13020250 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kesharwani, Prashant
Md, Shadab
Alhakamy, Nabil A.
Hosny, Khaled M.
Haque, Anzarul
QbD Enabled Azacitidine Loaded Liposomal Nanoformulation and Its In Vitro Evaluation
title QbD Enabled Azacitidine Loaded Liposomal Nanoformulation and Its In Vitro Evaluation
title_full QbD Enabled Azacitidine Loaded Liposomal Nanoformulation and Its In Vitro Evaluation
title_fullStr QbD Enabled Azacitidine Loaded Liposomal Nanoformulation and Its In Vitro Evaluation
title_full_unstemmed QbD Enabled Azacitidine Loaded Liposomal Nanoformulation and Its In Vitro Evaluation
title_short QbD Enabled Azacitidine Loaded Liposomal Nanoformulation and Its In Vitro Evaluation
title_sort qbd enabled azacitidine loaded liposomal nanoformulation and its in vitro evaluation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828524/
https://www.ncbi.nlm.nih.gov/pubmed/33451016
http://dx.doi.org/10.3390/polym13020250
work_keys_str_mv AT kesharwaniprashant qbdenabledazacitidineloadedliposomalnanoformulationanditsinvitroevaluation
AT mdshadab qbdenabledazacitidineloadedliposomalnanoformulationanditsinvitroevaluation
AT alhakamynabila qbdenabledazacitidineloadedliposomalnanoformulationanditsinvitroevaluation
AT hosnykhaledm qbdenabledazacitidineloadedliposomalnanoformulationanditsinvitroevaluation
AT haqueanzarul qbdenabledazacitidineloadedliposomalnanoformulationanditsinvitroevaluation