Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14C]-doxorubicin

Mas Jaffri Masarudin,1 Suzanne M Cutts,2 Benny J Evison,3 Don R Phillips,2 Paul J Pigram4 1Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 2Department of Biochemistry, La Trobe University, Melbourne, Victoria...

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Autores principales:	Masarudin MJ, Cutts SM, Evison BJ, Phillips DR, Pigram PJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Nanobiotechnology drug delivery chitosan chitosan nanoparticles doxorubicin FITC Medical technology R855-855.5 Chemical technology TP1-1185
Acceso en línea:	https://doaj.org/article/b49fd144f1ed4a4081771c863b7bf722
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spelling	oai:doaj.org-article:b49fd144f1ed4a4081771c863b7bf7222021-12-02T00:33:29ZFactors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14C]-doxorubicin1177-8903https://doaj.org/article/b49fd144f1ed4a4081771c863b7bf7222015-12-01T00:00:00Zhttps://www.dovepress.com/factors-determining-the-stability-size-distribution-and-cellular-accum-peer-reviewed-article-NSAhttps://doaj.org/toc/1177-8903Mas Jaffri Masarudin,1 Suzanne M Cutts,2 Benny J Evison,3 Don R Phillips,2 Paul J Pigram4 1Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 2Department of Biochemistry, La Trobe University, Melbourne, Victoria, Australia; 3Department of Chemical Biology and Therapeutics, St Jude Children's Hospital, Memphis, TN, USA; 4Department of Physics, La Trobe University, Melbourne, Victoria, Australia Abstract: Development of parameters for the fabrication of nanosized vectors is pivotal for its successful administration in therapeutic applications. In this study, homogeneously distributed chitosan nanoparticles (CNPs) with diameters as small as 62 nm and a polydispersity index (PDI) of 0.15 were synthesized and purified using a simple, robust method that was highly reproducible. Nanoparticles were synthesized using modified ionic gelation of the chitosan polymer with sodium tripolyphosphate. Using this method, larger aggregates were mechanically isolated from single particles in the nanoparticle population by selective efficient centrifugation. The presence of disaggregated monodisperse nanoparticles was confirmed using atomic force microscopy. Factors such as anions, pH, and concentration were found to affect the size and stability of nanoparticles directly. The smallest nanoparticle population was ~62 nm in hydrodynamic size, with a low PDI of 0.15, indicating high particle homogeneity. CNPs were highly stable and retained their monodisperse morphology in serum-supplemented media in cell culture conditions for up to 72 hours, before slowly degrading over 6 days. Cell viability assays demonstrated that cells remained viable following a 72-hour exposure to 1 mg/mL CNPs, suggesting that the nanoparticles are well tolerated and highly suited for biomedical applications. Cellular uptake studies using fluorescein isothiocyanate-labeled CNPs showed that cancer cells readily accumulate the nanoparticles 30 minutes posttreatment and that nanoparticles persisted within cells for up to 24 hours posttreatment. As a proof of principle for use in anticancer therapeutic applications, a [14C]-radiolabeled form of the anticancer agent doxorubicin was efficiently encapsulated within the CNP, confirming the feasibility of using this system as a drug delivery vector. Keywords: nanobiotechnology, drug delivery, chitosan, chitosan nanoparticles, doxorubicin, FITCMasarudin MJCutts SMEvison BJPhillips DRPigram PJDove Medical PressarticleNanobiotechnologydrug deliverychitosanchitosan nanoparticlesdoxorubicinFITCMedical technologyR855-855.5Chemical technologyTP1-1185ENNanotechnology, Science and Applications, Vol 2015, Iss Issue 1, Pp 67-80 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nanobiotechnology drug delivery chitosan chitosan nanoparticles doxorubicin FITC Medical technology R855-855.5 Chemical technology TP1-1185
spellingShingle	Nanobiotechnology drug delivery chitosan chitosan nanoparticles doxorubicin FITC Medical technology R855-855.5 Chemical technology TP1-1185 Masarudin MJ Cutts SM Evison BJ Phillips DR Pigram PJ Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14C]-doxorubicin
description	Mas Jaffri Masarudin,1 Suzanne M Cutts,2 Benny J Evison,3 Don R Phillips,2 Paul J Pigram4 1Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 2Department of Biochemistry, La Trobe University, Melbourne, Victoria, Australia; 3Department of Chemical Biology and Therapeutics, St Jude Children's Hospital, Memphis, TN, USA; 4Department of Physics, La Trobe University, Melbourne, Victoria, Australia Abstract: Development of parameters for the fabrication of nanosized vectors is pivotal for its successful administration in therapeutic applications. In this study, homogeneously distributed chitosan nanoparticles (CNPs) with diameters as small as 62 nm and a polydispersity index (PDI) of 0.15 were synthesized and purified using a simple, robust method that was highly reproducible. Nanoparticles were synthesized using modified ionic gelation of the chitosan polymer with sodium tripolyphosphate. Using this method, larger aggregates were mechanically isolated from single particles in the nanoparticle population by selective efficient centrifugation. The presence of disaggregated monodisperse nanoparticles was confirmed using atomic force microscopy. Factors such as anions, pH, and concentration were found to affect the size and stability of nanoparticles directly. The smallest nanoparticle population was ~62 nm in hydrodynamic size, with a low PDI of 0.15, indicating high particle homogeneity. CNPs were highly stable and retained their monodisperse morphology in serum-supplemented media in cell culture conditions for up to 72 hours, before slowly degrading over 6 days. Cell viability assays demonstrated that cells remained viable following a 72-hour exposure to 1 mg/mL CNPs, suggesting that the nanoparticles are well tolerated and highly suited for biomedical applications. Cellular uptake studies using fluorescein isothiocyanate-labeled CNPs showed that cancer cells readily accumulate the nanoparticles 30 minutes posttreatment and that nanoparticles persisted within cells for up to 24 hours posttreatment. As a proof of principle for use in anticancer therapeutic applications, a [14C]-radiolabeled form of the anticancer agent doxorubicin was efficiently encapsulated within the CNP, confirming the feasibility of using this system as a drug delivery vector. Keywords: nanobiotechnology, drug delivery, chitosan, chitosan nanoparticles, doxorubicin, FITC
format	article
author	Masarudin MJ Cutts SM Evison BJ Phillips DR Pigram PJ
author_facet	Masarudin MJ Cutts SM Evison BJ Phillips DR Pigram PJ
author_sort	Masarudin MJ
title	Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14C]-doxorubicin
title_short	Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14C]-doxorubicin
title_full	Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14C]-doxorubicin
title_fullStr	Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14C]-doxorubicin
title_full_unstemmed	Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14C]-doxorubicin
title_sort	factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14c]-doxorubicin
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/b49fd144f1ed4a4081771c863b7bf722
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Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14C]-doxorubicin

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