Doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan polymeric nanoformulation: uptake by cells and organs
Ummarah Kanwal,1,2 Nadeem Irfan Bukhari,2 Nosheen Fatima Rana,3 Mehreen Rehman,1 Khalid Hussain,2 Nasir Abbas,2 Arshad Mehmood,4 Abida Raza1 1NILOP Nanomedicine Research Laboratories, National Institute of Lasers and Optronics, Pakistan Institute of Engineering and Applied Sciences Islamabad, Pakis...
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Dove Medical Press
2018
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oai:doaj.org-article:032b18551415431b9651ee2d7184c35e2021-12-02T04:58:31ZDoxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan polymeric nanoformulation: uptake by cells and organs1178-2013https://doaj.org/article/032b18551415431b9651ee2d7184c35e2018-12-01T00:00:00Zhttps://www.dovepress.com/doxorubicin-loaded-quaternary-ammonium-palmitoyl-glycol-chitosan-polym-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ummarah Kanwal,1,2 Nadeem Irfan Bukhari,2 Nosheen Fatima Rana,3 Mehreen Rehman,1 Khalid Hussain,2 Nasir Abbas,2 Arshad Mehmood,4 Abida Raza1 1NILOP Nanomedicine Research Laboratories, National Institute of Lasers and Optronics, Pakistan Institute of Engineering and Applied Sciences Islamabad, Pakistan; 2University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore, Pakistan; 3Department of Biomedical Engineering and Sciences, School of Mechanical and Manufacturing Engineering, National University of Sciences and Technology, Islamabad, Pakistan; 4Material Division, National Institute of Lasers and Optronics, Pakistan Institute of Engineering and Applied Sciences Islamabad, Islamabad, Pakistan Purpose: This study was aimed to develop doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan (DOX–GCPQ) nanoformulation that could enable DOX delivery and noninvasive monitoring of drug accumulation and biodistribution at tumor site utilizing self-florescent property of doxorubicin.Materials and methods: DOX–GCPQ amphiphilic polymeric nanoformulations were prepared and optimized using artificial neural network (ANN) and characterized for surface morphology by atomic force microscopy, particle size with polydispersity index (PDI), and zeta potential by dynamic light scattering. Fourier transformed infrared (FTIR) and X-ray diffractometer studies were performed to examine drug polymer interaction. The ANN-optimized nanoformulation was investigated for in vitro release, cellular, tumor, and tissue uptake.Results: The optimized DOX–GCPQ nanoformulation was anionic spherical micelles with the hydrodynamic particle size of 97.8±1.5 nm, the PDI of <0.3, the zeta potential of 28±2 mV, and the encapsulation efficiency of 80%±1.5%. Nanoformulation demonstrated a sustained release pattern over 48 h, assuming Weibull model. Fluorescence microscopy revealed higher uptake of DOX–GCPQ in human rhabdomyosarcoma (RD) cells as compared to free DOX. In vitro cytotoxicity assay indicated a significant cytotoxicity of DOX–GCPQ against RD cells as compared to DOX and blank GCPQ (P<0.05). DOX–GCPQ exhibited low IC50 (1.7±0.404 µmol) when compared to that of DOX (3.0±0.968 µmol). In skin tumor xenografts, optical imaging revealed significantly lower DOX–GCPQ in heart and liver (P<0.05) and accumulated mainly in tumor (P<0.05) as compared to other tissues.Conclusion: The features of nanoformulation, ie, small particle size, sustained drug release, and enhanced cellular uptake, potential to target tumor passively coupled with the possibility of monitoring of tumor localization by optical imaging may make DOX–GCPQ an efficient nanotheranostic system. Keywords: quaternary ammonium palmitoyl glycol chitosan, doxorubicin, artificial neural network, optical imaging, biodistribution, nanotheranosticKanwal UBukhari NIRana NFRehman MHussain KAbbas NMehmood ARaza ADove Medical PressarticleQuaternary ammonium palmitoyl glycol chitosanDoxorubicinArtificial neural network (ANN)Optical imagingBiodistributionNanotheranosticMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 1-15 (2018) |
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DOAJ |
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Quaternary ammonium palmitoyl glycol chitosan Doxorubicin Artificial neural network (ANN) Optical imaging Biodistribution Nanotheranostic Medicine (General) R5-920 |
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Quaternary ammonium palmitoyl glycol chitosan Doxorubicin Artificial neural network (ANN) Optical imaging Biodistribution Nanotheranostic Medicine (General) R5-920 Kanwal U Bukhari NI Rana NF Rehman M Hussain K Abbas N Mehmood A Raza A Doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan polymeric nanoformulation: uptake by cells and organs |
description |
Ummarah Kanwal,1,2 Nadeem Irfan Bukhari,2 Nosheen Fatima Rana,3 Mehreen Rehman,1 Khalid Hussain,2 Nasir Abbas,2 Arshad Mehmood,4 Abida Raza1 1NILOP Nanomedicine Research Laboratories, National Institute of Lasers and Optronics, Pakistan Institute of Engineering and Applied Sciences Islamabad, Pakistan; 2University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore, Pakistan; 3Department of Biomedical Engineering and Sciences, School of Mechanical and Manufacturing Engineering, National University of Sciences and Technology, Islamabad, Pakistan; 4Material Division, National Institute of Lasers and Optronics, Pakistan Institute of Engineering and Applied Sciences Islamabad, Islamabad, Pakistan Purpose: This study was aimed to develop doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan (DOX–GCPQ) nanoformulation that could enable DOX delivery and noninvasive monitoring of drug accumulation and biodistribution at tumor site utilizing self-florescent property of doxorubicin.Materials and methods: DOX–GCPQ amphiphilic polymeric nanoformulations were prepared and optimized using artificial neural network (ANN) and characterized for surface morphology by atomic force microscopy, particle size with polydispersity index (PDI), and zeta potential by dynamic light scattering. Fourier transformed infrared (FTIR) and X-ray diffractometer studies were performed to examine drug polymer interaction. The ANN-optimized nanoformulation was investigated for in vitro release, cellular, tumor, and tissue uptake.Results: The optimized DOX–GCPQ nanoformulation was anionic spherical micelles with the hydrodynamic particle size of 97.8±1.5 nm, the PDI of <0.3, the zeta potential of 28±2 mV, and the encapsulation efficiency of 80%±1.5%. Nanoformulation demonstrated a sustained release pattern over 48 h, assuming Weibull model. Fluorescence microscopy revealed higher uptake of DOX–GCPQ in human rhabdomyosarcoma (RD) cells as compared to free DOX. In vitro cytotoxicity assay indicated a significant cytotoxicity of DOX–GCPQ against RD cells as compared to DOX and blank GCPQ (P<0.05). DOX–GCPQ exhibited low IC50 (1.7±0.404 µmol) when compared to that of DOX (3.0±0.968 µmol). In skin tumor xenografts, optical imaging revealed significantly lower DOX–GCPQ in heart and liver (P<0.05) and accumulated mainly in tumor (P<0.05) as compared to other tissues.Conclusion: The features of nanoformulation, ie, small particle size, sustained drug release, and enhanced cellular uptake, potential to target tumor passively coupled with the possibility of monitoring of tumor localization by optical imaging may make DOX–GCPQ an efficient nanotheranostic system. Keywords: quaternary ammonium palmitoyl glycol chitosan, doxorubicin, artificial neural network, optical imaging, biodistribution, nanotheranostic |
format |
article |
author |
Kanwal U Bukhari NI Rana NF Rehman M Hussain K Abbas N Mehmood A Raza A |
author_facet |
Kanwal U Bukhari NI Rana NF Rehman M Hussain K Abbas N Mehmood A Raza A |
author_sort |
Kanwal U |
title |
Doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan polymeric nanoformulation: uptake by cells and organs |
title_short |
Doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan polymeric nanoformulation: uptake by cells and organs |
title_full |
Doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan polymeric nanoformulation: uptake by cells and organs |
title_fullStr |
Doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan polymeric nanoformulation: uptake by cells and organs |
title_full_unstemmed |
Doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan polymeric nanoformulation: uptake by cells and organs |
title_sort |
doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan polymeric nanoformulation: uptake by cells and organs |
publisher |
Dove Medical Press |
publishDate |
2018 |
url |
https://doaj.org/article/032b18551415431b9651ee2d7184c35e |
work_keys_str_mv |
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