Northern Kentucky University

Investigating Mesoporous Organosilicates as Carriers for the Controlled, Local Delivery of the Chemotherapeutic Drug Doxorubicin Hydrochloride

Institution

Northern Kentucky University

Abstract

Currently, the most effective and common course of cancer treatment is the use of specialized chemotherapeutic drugs. When administered in high systemic doses, these drugs can cause severe toxicity to the healthy tissue cells, resulting in hair loss, nausea, anemia, and decreased immune response. One way to reduce this toxicity while delivering a high concentration of the drug directly at the tumor site is through drug encapsulation into delivery particulates. Our ongoing research has focused on mesoporous inorganic-based silica particles as possible carriers for the anticancer agent doxorubicin (Dox). These mesoporous silicates were synthesized without and with the presence of organic functional groups — sulfonate (SO3-Na+) and carboxylate (CO2-Na+) — that can interact with Dox through an ion-exchange process and increase the capability of conjugating Dox. The non-functionalized (SBA), the sulfonate (SBASO3-Na+) and carboxylate (SBA- CO2-Na+) functionalized mesoporous silicate materials, were treated with aqueous solutions of doxorubicin in a 4:1 solid-to-drug weight ratio. Based on their Dox-loading capacity, the materials can be ranked as follows: SBA- SO3-Na+ > SBA- CO2-Na+ > SBA, with SBA- SO3-Na+ capable of loading up to 200 mg of doxorubicin per gram of solid. The Dox-release profiles from the three Dox-loaded materials in saline solution (0.9 wt% NaCl) were monitored by UV-Vis at 37°C. The non-functionalized SBA material exhibits a rapid but incomplete (only 60%) and unreliable release of Dox. Dox releases completely from both SBASO3-DoxH+ and SBA-CO2-DoxH+, but more slowly from the former than the latter.

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Investigating Mesoporous Organosilicates as Carriers for the Controlled, Local Delivery of the Chemotherapeutic Drug Doxorubicin Hydrochloride

Currently, the most effective and common course of cancer treatment is the use of specialized chemotherapeutic drugs. When administered in high systemic doses, these drugs can cause severe toxicity to the healthy tissue cells, resulting in hair loss, nausea, anemia, and decreased immune response. One way to reduce this toxicity while delivering a high concentration of the drug directly at the tumor site is through drug encapsulation into delivery particulates. Our ongoing research has focused on mesoporous inorganic-based silica particles as possible carriers for the anticancer agent doxorubicin (Dox). These mesoporous silicates were synthesized without and with the presence of organic functional groups — sulfonate (SO3-Na+) and carboxylate (CO2-Na+) — that can interact with Dox through an ion-exchange process and increase the capability of conjugating Dox. The non-functionalized (SBA), the sulfonate (SBASO3-Na+) and carboxylate (SBA- CO2-Na+) functionalized mesoporous silicate materials, were treated with aqueous solutions of doxorubicin in a 4:1 solid-to-drug weight ratio. Based on their Dox-loading capacity, the materials can be ranked as follows: SBA- SO3-Na+ > SBA- CO2-Na+ > SBA, with SBA- SO3-Na+ capable of loading up to 200 mg of doxorubicin per gram of solid. The Dox-release profiles from the three Dox-loaded materials in saline solution (0.9 wt% NaCl) were monitored by UV-Vis at 37°C. The non-functionalized SBA material exhibits a rapid but incomplete (only 60%) and unreliable release of Dox. Dox releases completely from both SBASO3-DoxH+ and SBA-CO2-DoxH+, but more slowly from the former than the latter.