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 (CaCO3) 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.

The use of heat to deliver fentanyl via pulmonary drug delivery.

The golden standard to treat acute pain is by intravenous drug delivery of opioids such as fentanyl or morphine. Intravenous drug delivery requires the placement of an intravenous (IV) port, which can cause infections, dislodgments, and distress to the patients, and therefore a non-invasive method is desirable. Pulmonary drug delivery is a non-invasive method that has been shown to be a good alternative to intravenous administration. New devices have been investigated for treating acute pain by delivering fentanyl by heat. The pure drug, fentanyl, is applied onto a surface which is then heated up to 350 °C and inhaled, resulting in no formation of degradation products. Furthermore, forced degradation of fentanyl has been studied which showed that longer heating time and higher temperatures will result in the formation of degradation products. The evidence indicates that heat can be used to deliver drugs to the lungs where fast onset reaction can be obtained giving fast and non-invasive pain relief.