Entrapment of a Cytotoxic Drug into the Crystal Structure of Calcite for Targeted Drug Delivery

Controlled drug release and targeted drug delivery can reduce systemic toxicity of chemotherapeutics by restricting drugs to the target organ and increasing the local concentration. As tumors and inflamed tissue are often surrounded by an acidic microenvironment, pH-responsive calcium carbonates (Ca...

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Autores principales:	Amina Vazda, Michael Pujari-Palmer, Wei Xia, Håkan Engqvist
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	calcite target drug delivery pH-responsiveness in vitro MCF-7 Technology T Electrical engineering. Electronics. Nuclear engineering TK1-9971 Engineering (General). Civil engineering (General) TA1-2040 Microscopy QH201-278.5 Descriptive and experimental mechanics QC120-168.85
Acceso en línea:	https://doaj.org/article/2799c9b8e2374f878866a71c3aa50686
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spelling	oai:doaj.org-article:2799c9b8e2374f878866a71c3aa506862021-11-25T18:13:09ZEntrapment of a Cytotoxic Drug into the Crystal Structure of Calcite for Targeted Drug Delivery10.3390/ma142267351996-1944https://doaj.org/article/2799c9b8e2374f878866a71c3aa506862021-11-01T00:00:00Zhttps://www.mdpi.com/1996-1944/14/22/6735https://doaj.org/toc/1996-1944Controlled drug release and targeted drug delivery can reduce systemic toxicity of chemotherapeutics by restricting drugs to the target organ and increasing the local concentration. As tumors and inflamed tissue are often surrounded by an acidic microenvironment, pH-responsive calcium carbonates (CaCO<sub>3</sub>) are promising vehicles for controlled drug delivery applications. The aim of this study was to evaluate the loading efficacy and release of a chemotherapeutic drug, Hydroxyurea (HU), into the crystal structure of calcite. Incorporation of HU did not alter the crystallinity, crystal size, or morphology of precipitated calcite crystals, as assessed by XRD and SEM. The amount of HU was quantified by High-Pressure Liquid Chromatography (HPLC) and showed that 6.7 ± 0.7 µg of HU could be for each milligram of calcite (0.016 mol% ± 0.002). In cell media, the optimal pH for controlled release was 5 (0.1 mg/mL released after 1 h). However, in vitro, pH below 6.5 was cytotoxic to human breast cancer cells (MCF-7). Direct contact studies, where particles were incubated with MCF-7 cells, showed that the amount of HU release from calcite was not high enough to kill the cell or arrest growth at pH 6.5. Pre-dissolved release studies, where the particles were pre-dissolved in acidic media to simulate complete drug release in vivo, pH neutralized, and exposed to the cells, showed that the amount of loaded HU reduced the survival/proliferation of MCF7. In conclusion, it is possible to integrate HU into the crystal structure of a calcite crystal and release the drug in vitro at concentrations that can slow the growth of cancer cells, without affecting calcite morphology and crystallinity. Further research is needed to investigate the in vivo behavior of the particles and whether the actual tumor pH is low enough to achieve complete drug release in vivo.Amina VazdaMichael Pujari-PalmerWei XiaHåkan EngqvistMDPI AGarticlecalcitetarget drug deliverypH-responsivenessin vitroMCF-7TechnologyTElectrical engineering. Electronics. Nuclear engineeringTK1-9971Engineering (General). Civil engineering (General)TA1-2040MicroscopyQH201-278.5Descriptive and experimental mechanicsQC120-168.85ENMaterials, Vol 14, Iss 6735, p 6735 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	calcite target drug delivery pH-responsiveness in vitro MCF-7 Technology T Electrical engineering. Electronics. Nuclear engineering TK1-9971 Engineering (General). Civil engineering (General) TA1-2040 Microscopy QH201-278.5 Descriptive and experimental mechanics QC120-168.85
spellingShingle	calcite target drug delivery pH-responsiveness in vitro MCF-7 Technology T Electrical engineering. Electronics. Nuclear engineering TK1-9971 Engineering (General). Civil engineering (General) TA1-2040 Microscopy QH201-278.5 Descriptive and experimental mechanics QC120-168.85 Amina Vazda Michael Pujari-Palmer Wei Xia Håkan Engqvist Entrapment of a Cytotoxic Drug into the Crystal Structure of Calcite for Targeted Drug Delivery
description	Controlled drug release and targeted drug delivery can reduce systemic toxicity of chemotherapeutics by restricting drugs to the target organ and increasing the local concentration. As tumors and inflamed tissue are often surrounded by an acidic microenvironment, pH-responsive calcium carbonates (CaCO<sub>3</sub>) are promising vehicles for controlled drug delivery applications. The aim of this study was to evaluate the loading efficacy and release of a chemotherapeutic drug, Hydroxyurea (HU), into the crystal structure of calcite. Incorporation of HU did not alter the crystallinity, crystal size, or morphology of precipitated calcite crystals, as assessed by XRD and SEM. The amount of HU was quantified by High-Pressure Liquid Chromatography (HPLC) and showed that 6.7 ± 0.7 µg of HU could be for each milligram of calcite (0.016 mol% ± 0.002). In cell media, the optimal pH for controlled release was 5 (0.1 mg/mL released after 1 h). However, in vitro, pH below 6.5 was cytotoxic to human breast cancer cells (MCF-7). Direct contact studies, where particles were incubated with MCF-7 cells, showed that the amount of HU release from calcite was not high enough to kill the cell or arrest growth at pH 6.5. Pre-dissolved release studies, where the particles were pre-dissolved in acidic media to simulate complete drug release in vivo, pH neutralized, and exposed to the cells, showed that the amount of loaded HU reduced the survival/proliferation of MCF7. In conclusion, it is possible to integrate HU into the crystal structure of a calcite crystal and release the drug in vitro at concentrations that can slow the growth of cancer cells, without affecting calcite morphology and crystallinity. Further research is needed to investigate the in vivo behavior of the particles and whether the actual tumor pH is low enough to achieve complete drug release in vivo.
format	article
author	Amina Vazda Michael Pujari-Palmer Wei Xia Håkan Engqvist
author_facet	Amina Vazda Michael Pujari-Palmer Wei Xia Håkan Engqvist
author_sort	Amina Vazda
title	Entrapment of a Cytotoxic Drug into the Crystal Structure of Calcite for Targeted Drug Delivery
title_short	Entrapment of a Cytotoxic Drug into the Crystal Structure of Calcite for Targeted Drug Delivery
title_full	Entrapment of a Cytotoxic Drug into the Crystal Structure of Calcite for Targeted Drug Delivery
title_fullStr	Entrapment of a Cytotoxic Drug into the Crystal Structure of Calcite for Targeted Drug Delivery
title_full_unstemmed	Entrapment of a Cytotoxic Drug into the Crystal Structure of Calcite for Targeted Drug Delivery
title_sort	entrapment of a cytotoxic drug into the crystal structure of calcite for targeted drug delivery
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2799c9b8e2374f878866a71c3aa50686
work_keys_str_mv	AT aminavazda entrapmentofacytotoxicdrugintothecrystalstructureofcalcitefortargeteddrugdelivery AT michaelpujaripalmer entrapmentofacytotoxicdrugintothecrystalstructureofcalcitefortargeteddrugdelivery AT weixia entrapmentofacytotoxicdrugintothecrystalstructureofcalcitefortargeteddrugdelivery AT hakanengqvist entrapmentofacytotoxicdrugintothecrystalstructureofcalcitefortargeteddrugdelivery
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Entrapment of a Cytotoxic Drug into the Crystal Structure of Calcite for Targeted Drug Delivery

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