In vitro cellular localization and efficient accumulation of fluorescently tagged biomaterials from monodispersed chitosan nanoparticles for elucidation of controlled release pathways for drug delivery systems

Ummu Afiqah Hassan,1 Mohd Zobir Hussein,2 Noorjahan Banu Alitheen,1 Syazaira Arham Yahya Ariff,1 Mas Jaffri Masarudin1,2 1Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Material Synthesis and Cha...

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Autores principales:	Hassan UA, Hussein MZ, Alitheen NB, Yahya Ariff SA, Masarudin MJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	drug delivery nanotechnology chitosan glutamic acid FITC Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7ed636c251d342eda4354c0b7d41084a
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spelling	oai:doaj.org-article:7ed636c251d342eda4354c0b7d41084a2021-12-02T03:14:17ZIn vitro cellular localization and efficient accumulation of fluorescently tagged biomaterials from monodispersed chitosan nanoparticles for elucidation of controlled release pathways for drug delivery systems1178-2013https://doaj.org/article/7ed636c251d342eda4354c0b7d41084a2018-09-01T00:00:00Zhttps://www.dovepress.com/in-vitro-cellular-localization-and-efficient-accumulation-of-fluoresce-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ummu Afiqah Hassan,1 Mohd Zobir Hussein,2 Noorjahan Banu Alitheen,1 Syazaira Arham Yahya Ariff,1 Mas Jaffri Masarudin1,2 1Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Material Synthesis and Characterization Laboratory, Institute of Advanced Technology, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Background: Inefficient cellular delivery and poor intracellular accumulation are major drawbacks towards achieving favorable therapeutic responses from many therapeutic drugs and biomolecules. To tackle this issue, nanoparticle-mediated delivery vectors have been aptly explored as a promising delivery strategy capable of enhancing the cellular localization of biomolecules and improve their therapeutic efficacies. However, the dynamics of intracellular biomolecule release and accumulation from such nanoparticle systems has currently remained scarcely studied. Objectives: The objective of this study was to utilize a chitosan-based nanoparticle system as the delivery carrier for glutamic acid, a model for encapsulated biomolecules to visualize the in vitro release and accumulation of the encapsulated glutamic acid from chitosan nanoparticle (CNP) systems. Methods: CNP was synthesized via ionic gelation routes utilizing tripolyphosphate (TPP) as a cross-linker. In order to track glutamic acid release, the glutamic acid was fluorescently-labeled with fluorescein isothiocyanate prior encapsulation into CNP. Results: Light Scattering data concluded the successful formation of small-sized and monodispersed CNP at a specific volume ratio of chitosan to TPP. Encapsulation of glutamic acid as a model cargo into CNP led to an increase in particle size to >100 nm. The synthesized CNP exhibited spherical shape under Electron Microscopy. The formation of CNP was reflected by the reduction in free amine groups of chitosan following ionic crosslinking reactions. The encapsulation of glutamic acid was further confirmed by Fourier Transform Infrared (FTIR) analysis. Cell viability assay showed 70% cell viability at the maximum concentration of 0.5 mg/mL CS and 0.7 mg/mL TPP used, indicating the low inherent toxicity property of this system. In vitro release study using fluorescently-tagged glutamic acids demonstrated the release and accumulation of the encapsulated glutamic acids at 6 hours post treatment. A significant accumulation was observed at 24 hours and 48 hours later. Flow cytometry data demonstrated a gradual increase in intracellular fluorescence signal from 30 minutes to 48 hours post treatment with fluorescently-labeled glutamic acids encapsulated CNP. Conclusion: These results therefore suggested the potential of CNP system towards enhancing the intracellular delivery and release of the encapsulated glutamic acids. This CNP system thus may serves as a potential candidate vector capable to improve the therapeutic efficacy for drugs and biomolecules in medical as well as pharmaceutical applications through the enhanced intracellular release and accumulation of the encapsulated cargo. Keywords: drug delivery, nanotechnology, chitosan, glutamic acid, FITCHassan UAHussein MZAlitheen NBYahya Ariff SAMasarudin MJDove Medical Pressarticledrug deliverynanotechnologychitosanglutamic acidFITCMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 5075-5095 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	drug delivery nanotechnology chitosan glutamic acid FITC Medicine (General) R5-920
spellingShingle	drug delivery nanotechnology chitosan glutamic acid FITC Medicine (General) R5-920 Hassan UA Hussein MZ Alitheen NB Yahya Ariff SA Masarudin MJ In vitro cellular localization and efficient accumulation of fluorescently tagged biomaterials from monodispersed chitosan nanoparticles for elucidation of controlled release pathways for drug delivery systems
description	Ummu Afiqah Hassan,1 Mohd Zobir Hussein,2 Noorjahan Banu Alitheen,1 Syazaira Arham Yahya Ariff,1 Mas Jaffri Masarudin1,2 1Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Material Synthesis and Characterization Laboratory, Institute of Advanced Technology, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Background: Inefficient cellular delivery and poor intracellular accumulation are major drawbacks towards achieving favorable therapeutic responses from many therapeutic drugs and biomolecules. To tackle this issue, nanoparticle-mediated delivery vectors have been aptly explored as a promising delivery strategy capable of enhancing the cellular localization of biomolecules and improve their therapeutic efficacies. However, the dynamics of intracellular biomolecule release and accumulation from such nanoparticle systems has currently remained scarcely studied. Objectives: The objective of this study was to utilize a chitosan-based nanoparticle system as the delivery carrier for glutamic acid, a model for encapsulated biomolecules to visualize the in vitro release and accumulation of the encapsulated glutamic acid from chitosan nanoparticle (CNP) systems. Methods: CNP was synthesized via ionic gelation routes utilizing tripolyphosphate (TPP) as a cross-linker. In order to track glutamic acid release, the glutamic acid was fluorescently-labeled with fluorescein isothiocyanate prior encapsulation into CNP. Results: Light Scattering data concluded the successful formation of small-sized and monodispersed CNP at a specific volume ratio of chitosan to TPP. Encapsulation of glutamic acid as a model cargo into CNP led to an increase in particle size to >100 nm. The synthesized CNP exhibited spherical shape under Electron Microscopy. The formation of CNP was reflected by the reduction in free amine groups of chitosan following ionic crosslinking reactions. The encapsulation of glutamic acid was further confirmed by Fourier Transform Infrared (FTIR) analysis. Cell viability assay showed 70% cell viability at the maximum concentration of 0.5 mg/mL CS and 0.7 mg/mL TPP used, indicating the low inherent toxicity property of this system. In vitro release study using fluorescently-tagged glutamic acids demonstrated the release and accumulation of the encapsulated glutamic acids at 6 hours post treatment. A significant accumulation was observed at 24 hours and 48 hours later. Flow cytometry data demonstrated a gradual increase in intracellular fluorescence signal from 30 minutes to 48 hours post treatment with fluorescently-labeled glutamic acids encapsulated CNP. Conclusion: These results therefore suggested the potential of CNP system towards enhancing the intracellular delivery and release of the encapsulated glutamic acids. This CNP system thus may serves as a potential candidate vector capable to improve the therapeutic efficacy for drugs and biomolecules in medical as well as pharmaceutical applications through the enhanced intracellular release and accumulation of the encapsulated cargo. Keywords: drug delivery, nanotechnology, chitosan, glutamic acid, FITC
format	article
author	Hassan UA Hussein MZ Alitheen NB Yahya Ariff SA Masarudin MJ
author_facet	Hassan UA Hussein MZ Alitheen NB Yahya Ariff SA Masarudin MJ
author_sort	Hassan UA
title	In vitro cellular localization and efficient accumulation of fluorescently tagged biomaterials from monodispersed chitosan nanoparticles for elucidation of controlled release pathways for drug delivery systems
title_short	In vitro cellular localization and efficient accumulation of fluorescently tagged biomaterials from monodispersed chitosan nanoparticles for elucidation of controlled release pathways for drug delivery systems
title_full	In vitro cellular localization and efficient accumulation of fluorescently tagged biomaterials from monodispersed chitosan nanoparticles for elucidation of controlled release pathways for drug delivery systems
title_fullStr	In vitro cellular localization and efficient accumulation of fluorescently tagged biomaterials from monodispersed chitosan nanoparticles for elucidation of controlled release pathways for drug delivery systems
title_full_unstemmed	In vitro cellular localization and efficient accumulation of fluorescently tagged biomaterials from monodispersed chitosan nanoparticles for elucidation of controlled release pathways for drug delivery systems
title_sort	in vitro cellular localization and efficient accumulation of fluorescently tagged biomaterials from monodispersed chitosan nanoparticles for elucidation of controlled release pathways for drug delivery systems
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/7ed636c251d342eda4354c0b7d41084a
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_version_	1718401865871261696

In vitro cellular localization and efficient accumulation of fluorescently tagged biomaterials from monodispersed chitosan nanoparticles for elucidation of controlled release pathways for drug delivery systems

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