Lyophilization and stability of antibody-conjugated mesoporous silica nanoparticle with cationic polymer and PEG for siRNA delivery

Worapol Ngamcherdtrakul,1,2,* Thanapon Sangvanich,1,* Moataz Reda,1 Shenda Gu,1 Daniel Bejan,2 Wassana Yantasee1,2 1Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA; 2Nanomedicine Research Unit, PDX Pharmaceuticals, LLC, Portland, OR, USA *These authors...

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Autores principales:	Ngamcherdtrakul W, Sangvanich T, Reda M, Gu S, Bejan D, Yantasee W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	nanoparticles lyophilization cancer mesoporous silica antibody siRNA Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1c2b5c3efd984b3daf1e086e7adb7287
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spelling	oai:doaj.org-article:1c2b5c3efd984b3daf1e086e7adb72872021-12-02T02:57:17ZLyophilization and stability of antibody-conjugated mesoporous silica nanoparticle with cationic polymer and PEG for siRNA delivery1178-2013https://doaj.org/article/1c2b5c3efd984b3daf1e086e7adb72872018-07-01T00:00:00Zhttps://www.dovepress.com/lyophilization-and-stability-of-antibody-conjugated-mesoporous-silica--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Worapol Ngamcherdtrakul,1,2,* Thanapon Sangvanich,1,* Moataz Reda,1 Shenda Gu,1 Daniel Bejan,2 Wassana Yantasee1,2 1Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA; 2Nanomedicine Research Unit, PDX Pharmaceuticals, LLC, Portland, OR, USA *These authors contributed equally to this work Introduction: Long-term stability of therapeutic candidates is necessary toward their clinical applications. For most nanoparticle systems formulated in aqueous solutions, lyophilization or freeze-drying is a common method to ensure long-term stability. While lyophilization of lipid, polymeric, or inorganic nanoparticles have been studied, little has been reported on lyophilization and stability of hybrid nanoparticle systems, consisting of polymers, inorganic particles, and antibody. Lyophilization of complex nanoparticle systems can be challenging with respect to preserving physicochemical properties and the biological activities of the materials. We recently reported an effective small-interfering RNA (siRNA) nanoparticle carrier consisting of 50-nm mesoporous silica nanoparticles decorated with a copolymer of polyethylenimine and polyethyleneglycol, and antibody. Materials and methods: Toward future personalized medicine, the nanoparticle carriers were lyophilized alone and loaded with siRNA upon reconstitution by a few minutes of simple mixing in phosphate-buffered saline. Herein, we optimize the lyophilization of the nanoparticles in terms of buffers, lyoprotectants, reconstitution, and time and temperature of freezing and drying steps, and monitor the physical and chemical properties (reconstitution, hydrodynamic size, charge, and siRNA loading) and biological activities (gene silencing, cancer cell killing) of the materials after storing at various temperatures and times. Results: The material was best formulated in Tris-HCl buffer with 5% w/w trehalose. Freezing step was performed at -55°C for 3 h, followed by a primary drying step at -40°C (100 μBar) for 24 h and a secondary drying step at 20°C (20 μBar) for 12 h. The lyophilized material can be stored stably for 2 months at 4°C and at least 6 months at -20°C. Conclusion: We successfully developed the lyophilization process that should be applicable to other similar nanoparticle systems consisting of inorganic nanoparticle cores modified with cationic polymers, PEG, and antibodies. Keywords: nanoparticles, lyophilization, cancer, mesoporous silica, antibody, siRNANgamcherdtrakul WSangvanich TReda MGu SBejan DYantasee WDove Medical Pressarticlenanoparticleslyophilizationcancermesoporous silicaantibodysiRNAMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 4015-4027 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanoparticles lyophilization cancer mesoporous silica antibody siRNA Medicine (General) R5-920
spellingShingle	nanoparticles lyophilization cancer mesoporous silica antibody siRNA Medicine (General) R5-920 Ngamcherdtrakul W Sangvanich T Reda M Gu S Bejan D Yantasee W Lyophilization and stability of antibody-conjugated mesoporous silica nanoparticle with cationic polymer and PEG for siRNA delivery
description	Worapol Ngamcherdtrakul,1,2,* Thanapon Sangvanich,1,* Moataz Reda,1 Shenda Gu,1 Daniel Bejan,2 Wassana Yantasee1,2 1Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA; 2Nanomedicine Research Unit, PDX Pharmaceuticals, LLC, Portland, OR, USA *These authors contributed equally to this work Introduction: Long-term stability of therapeutic candidates is necessary toward their clinical applications. For most nanoparticle systems formulated in aqueous solutions, lyophilization or freeze-drying is a common method to ensure long-term stability. While lyophilization of lipid, polymeric, or inorganic nanoparticles have been studied, little has been reported on lyophilization and stability of hybrid nanoparticle systems, consisting of polymers, inorganic particles, and antibody. Lyophilization of complex nanoparticle systems can be challenging with respect to preserving physicochemical properties and the biological activities of the materials. We recently reported an effective small-interfering RNA (siRNA) nanoparticle carrier consisting of 50-nm mesoporous silica nanoparticles decorated with a copolymer of polyethylenimine and polyethyleneglycol, and antibody. Materials and methods: Toward future personalized medicine, the nanoparticle carriers were lyophilized alone and loaded with siRNA upon reconstitution by a few minutes of simple mixing in phosphate-buffered saline. Herein, we optimize the lyophilization of the nanoparticles in terms of buffers, lyoprotectants, reconstitution, and time and temperature of freezing and drying steps, and monitor the physical and chemical properties (reconstitution, hydrodynamic size, charge, and siRNA loading) and biological activities (gene silencing, cancer cell killing) of the materials after storing at various temperatures and times. Results: The material was best formulated in Tris-HCl buffer with 5% w/w trehalose. Freezing step was performed at -55°C for 3 h, followed by a primary drying step at -40°C (100 μBar) for 24 h and a secondary drying step at 20°C (20 μBar) for 12 h. The lyophilized material can be stored stably for 2 months at 4°C and at least 6 months at -20°C. Conclusion: We successfully developed the lyophilization process that should be applicable to other similar nanoparticle systems consisting of inorganic nanoparticle cores modified with cationic polymers, PEG, and antibodies. Keywords: nanoparticles, lyophilization, cancer, mesoporous silica, antibody, siRNA
format	article
author	Ngamcherdtrakul W Sangvanich T Reda M Gu S Bejan D Yantasee W
author_facet	Ngamcherdtrakul W Sangvanich T Reda M Gu S Bejan D Yantasee W
author_sort	Ngamcherdtrakul W
title	Lyophilization and stability of antibody-conjugated mesoporous silica nanoparticle with cationic polymer and PEG for siRNA delivery
title_short	Lyophilization and stability of antibody-conjugated mesoporous silica nanoparticle with cationic polymer and PEG for siRNA delivery
title_full	Lyophilization and stability of antibody-conjugated mesoporous silica nanoparticle with cationic polymer and PEG for siRNA delivery
title_fullStr	Lyophilization and stability of antibody-conjugated mesoporous silica nanoparticle with cationic polymer and PEG for siRNA delivery
title_full_unstemmed	Lyophilization and stability of antibody-conjugated mesoporous silica nanoparticle with cationic polymer and PEG for siRNA delivery
title_sort	lyophilization and stability of antibody-conjugated mesoporous silica nanoparticle with cationic polymer and peg for sirna delivery
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/1c2b5c3efd984b3daf1e086e7adb7287
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Lyophilization and stability of antibody-conjugated mesoporous silica nanoparticle with cationic polymer and PEG for siRNA delivery

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