Magnetically controlled protein nanocontainers as a drug depot for the hemostatic agent

Artur Prilepskii, Alexandra Schekina, Vladimir VinogradovITMO University, International Institute “Solution Chemistry of Advanced Materials and Technologies” (SCAMT), Saint Petersburg 191002, Russian FederationPurpose: Currently, there is a number of successfully implemented loca...

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Autores principales:	Prilepskii A, Schekina A, Vinogradov V
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Protein nanocontainers magnetite nanoparticles hemostasis -aminocaproic acid drug delivery Medical technology R855-855.5 Chemical technology TP1-1185
Acceso en línea:	https://doaj.org/article/066984274cb3449989c4f5cd27ebf04a
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spelling	oai:doaj.org-article:066984274cb3449989c4f5cd27ebf04a2021-12-02T03:05:09ZMagnetically controlled protein nanocontainers as a drug depot for the hemostatic agent1177-8903https://doaj.org/article/066984274cb3449989c4f5cd27ebf04a2019-07-01T00:00:00Zhttps://www.dovepress.com/magnetically-controlled-protein-nanocontainers-as-a-drug-depot-for-the-peer-reviewed-article-NSAhttps://doaj.org/toc/1177-8903Artur Prilepskii, Alexandra Schekina, Vladimir VinogradovITMO University, International Institute “Solution Chemistry of Advanced Materials and Technologies” (SCAMT), Saint Petersburg 191002, Russian FederationPurpose: Currently, there is a number of successfully implemented local hemostatic agents for external bleedings in forms of wound dressings and other topical materials. However, little has been done in the field of intravenous hemostatic agents. Here, we propose a new procedure to fabricate biocompatible protein nanocontainers (NCs) for intravenous injection allowing magneto-controllable delivery and short-term release of the hemostatic agent ϵ-aminocaproic acid (EACA).Methods: The nanocontainers were synthesized by the desolvation method from bovine serum albumin (BSA) using methanol without any further crosslinking. Polyethylene glycol (PEG) was used both as a stabilization agent and for size control. Characterization of nanocontainers was performed by the transmission and scanning electron microscopy, dynamic light scattering, X-ray diffraction, and FTIR spectroscopy. Cytotoxicity was estimated using MTT assay. The dopant release from nanocontainers was measured spectrophotometrically using rhodamine B as a model molecule. The specific hemostatic activity was assessed by analyzing clot lysis and formation curve (CloFAL). Moreover, the ability for magneto targeting was estimated using the original flow setup made of a syringe pump and silicon contours.Results: Fabricated nanocontainers had an average size of 186±24 nm and were constructed from building blocks–nanoparticles with average size ranged from 10 to 20 nm. PEG shell was also observed around nanocontainers with thickness 5–10 nm. NCs were proved to be completely non-cytotoxic even at concentrations up to 8 mg BSA/mL. Uptake capacity was near 36% while release within the first day was 17%. The analysis of the CloFAL curve showed the ability of NCs to inhibit the clot lysis successfully, and the ability of magneto targeting was confirmed under flow conditions.Conclusion: The ability of synthesized NCs to deliver and release the therapeutic drug, as well as to accumulate at the desired site under the action of the magnetic field was proved experimentally.Keywords: protein nanocontainers, magnetite nanoparticles, hemostasis, ϵ-aminocaproic acid, drug deliveryPrilepskii ASchekina AVinogradov VDove Medical PressarticleProtein nanocontainersmagnetite nanoparticleshemostasis-aminocaproic aciddrug deliveryMedical technologyR855-855.5Chemical technologyTP1-1185ENNanotechnology, Science and Applications, Vol Volume 12, Pp 11-23 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Protein nanocontainers magnetite nanoparticles hemostasis -aminocaproic acid drug delivery Medical technology R855-855.5 Chemical technology TP1-1185
spellingShingle	Protein nanocontainers magnetite nanoparticles hemostasis -aminocaproic acid drug delivery Medical technology R855-855.5 Chemical technology TP1-1185 Prilepskii A Schekina A Vinogradov V Magnetically controlled protein nanocontainers as a drug depot for the hemostatic agent
description	Artur Prilepskii, Alexandra Schekina, Vladimir VinogradovITMO University, International Institute “Solution Chemistry of Advanced Materials and Technologies” (SCAMT), Saint Petersburg 191002, Russian FederationPurpose: Currently, there is a number of successfully implemented local hemostatic agents for external bleedings in forms of wound dressings and other topical materials. However, little has been done in the field of intravenous hemostatic agents. Here, we propose a new procedure to fabricate biocompatible protein nanocontainers (NCs) for intravenous injection allowing magneto-controllable delivery and short-term release of the hemostatic agent ϵ-aminocaproic acid (EACA).Methods: The nanocontainers were synthesized by the desolvation method from bovine serum albumin (BSA) using methanol without any further crosslinking. Polyethylene glycol (PEG) was used both as a stabilization agent and for size control. Characterization of nanocontainers was performed by the transmission and scanning electron microscopy, dynamic light scattering, X-ray diffraction, and FTIR spectroscopy. Cytotoxicity was estimated using MTT assay. The dopant release from nanocontainers was measured spectrophotometrically using rhodamine B as a model molecule. The specific hemostatic activity was assessed by analyzing clot lysis and formation curve (CloFAL). Moreover, the ability for magneto targeting was estimated using the original flow setup made of a syringe pump and silicon contours.Results: Fabricated nanocontainers had an average size of 186±24 nm and were constructed from building blocks–nanoparticles with average size ranged from 10 to 20 nm. PEG shell was also observed around nanocontainers with thickness 5–10 nm. NCs were proved to be completely non-cytotoxic even at concentrations up to 8 mg BSA/mL. Uptake capacity was near 36% while release within the first day was 17%. The analysis of the CloFAL curve showed the ability of NCs to inhibit the clot lysis successfully, and the ability of magneto targeting was confirmed under flow conditions.Conclusion: The ability of synthesized NCs to deliver and release the therapeutic drug, as well as to accumulate at the desired site under the action of the magnetic field was proved experimentally.Keywords: protein nanocontainers, magnetite nanoparticles, hemostasis, ϵ-aminocaproic acid, drug delivery
format	article
author	Prilepskii A Schekina A Vinogradov V
author_facet	Prilepskii A Schekina A Vinogradov V
author_sort	Prilepskii A
title	Magnetically controlled protein nanocontainers as a drug depot for the hemostatic agent
title_short	Magnetically controlled protein nanocontainers as a drug depot for the hemostatic agent
title_full	Magnetically controlled protein nanocontainers as a drug depot for the hemostatic agent
title_fullStr	Magnetically controlled protein nanocontainers as a drug depot for the hemostatic agent
title_full_unstemmed	Magnetically controlled protein nanocontainers as a drug depot for the hemostatic agent
title_sort	magnetically controlled protein nanocontainers as a drug depot for the hemostatic agent
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/066984274cb3449989c4f5cd27ebf04a
work_keys_str_mv	AT prilepskiia magneticallycontrolledproteinnanocontainersasadrugdepotforthehemostaticagent AT schekinaa magneticallycontrolledproteinnanocontainersasadrugdepotforthehemostaticagent AT vinogradovv magneticallycontrolledproteinnanocontainersasadrugdepotforthehemostaticagent
_version_	1718401960597520384

Magnetically controlled protein nanocontainers as a drug depot for the hemostatic agent

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