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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MDPI AG
2021-11-01
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| Online Access: | https://www.mdpi.com/1996-1944/14/22/6735 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:19:29Z |
| format | Article |
| id | doaj.art-2799c9b8e2374f878866a71c3aa50686 |
| institution | Directory Open Access Journal |
| issn | 1996-1944 |
| language | English |
| last_indexed | 2024-03-10T05:19:29Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Materials |
| spelling | doaj.art-2799c9b8e2374f878866a71c3aa506862023-11-23T00:07:53ZengMDPI AGMaterials1996-19442021-11-011422673510.3390/ma14226735Entrapment of a Cytotoxic Drug into the Crystal Structure of Calcite for Targeted Drug DeliveryAmina Vazda0Michael Pujari-Palmer1Wei Xia2Håkan Engqvist3Department of Materials Science and Engineering, Division of Applied Materials Science, Uppsala University, 75121 Uppsala, SwedenDepartment of Materials Science and Engineering, Division of Applied Materials Science, Uppsala University, 75121 Uppsala, SwedenDepartment of Materials Science and Engineering, Division of Applied Materials Science, Uppsala University, 75121 Uppsala, SwedenDepartment of Materials Science and Engineering, Division of Applied Materials Science, Uppsala University, 75121 Uppsala, SwedenControlled 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.https://www.mdpi.com/1996-1944/14/22/6735calcitetarget drug deliverypH-responsivenessin vitroMCF-7 |
| spellingShingle | Amina Vazda Michael Pujari-Palmer Wei Xia Håkan Engqvist Entrapment of a Cytotoxic Drug into the Crystal Structure of Calcite for Targeted Drug Delivery Materials calcite target drug delivery pH-responsiveness in vitro MCF-7 |
| title | 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_short | 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 |
| topic | calcite target drug delivery pH-responsiveness in vitro MCF-7 |
| url | https://www.mdpi.com/1996-1944/14/22/6735 |
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