Synthesis and Characterization of Hollow Core-Shell Silica Nanoparticles as Drug Delivery Vector

Abstract

Nanodrug carriers are found to be better choice in the treatment of benign cancerous tumors which deliver small dosages of drugs specific to the diseased area. Scarcity in the emergence of new drug carriers with specific features like targeted delivery, higher drug loading capacity and biocompatibility has enhanced the research interest in them. Hollow core-shell silica nanoparticles (HCSNs) are being considered as one of the most favorable nanodrug carriers to accomplish targeted drug delivery, due to their unique properties like large surface area, tunable thickness, tunable pore diameter, low density, high chemical/thermal stability and good biocompatibility. In the present research work, we report a simple two-step method to synthesize HCSNs. HCSNs are synthesized using sacrificial template method. Polystyrene nanoparticles and funtionalized polystyrene nanoparticles (sulfonate and nitro functionalization) are used as sacrificial templates to obtain desirable morphology for the HCSNs. Polymer templates are synthesized in the first step and they are used as sacrificial templates in the second step during the synthesis of HCSNs by modified Stober method. Effect of the parameters like water-ethanol volume ratio, concentration of ammonia, concentration of cetyl trimethylammonium bromide (CTAB) and PS/tetraethyl orthosilicate (TEOS) weight ratio on morphology of HCSNs is analyzed. Further, polystyrene nanoparticles are functionalized to improve the surface charge properties by sulfonation and nitration. Functionalized PS nanoparticles are used as templates for the synthesis of HCSNs with enhanced shell thickness and pore size respectively. Effect of surface area, thickness of the silica shell and pore size on drug release from HCSNs are studied in detail using doxorubicin as a model drug. Application of HCSNs synthesized using sulfonated PS in sustained release of doxorubicin is found to be advantageous compared to the other synthesized samples. The properties of HCSNs samples synthesized using sulfonated PS such as higher shell thickness and pore size lead to higher encapsulation efficiency with sustained release of doxorubicin for 300 minutes. SPION embedded HCSNs are synthesized by sacrificial PS ii template method. Presence of SPION is an added advantage which aided radio frequency heating of the nanoparticles and allowed to study the variation of SPION concentration on the temperature rise. The release of drug from the SPION embedded HCSNs are found to be temperature dependant. The doxorubicin release kinetic profiles of HCSNs and SPION embedded HCSNs are studied using models such as zero order, first order and Higuchi model. Release kinetics showed best fit for first order model. In vitro cytotoxicity assays carried out on normal cells and cancer cells confirmed the biocompatibility of HCSNs and SPION embedded HCSNs. However, doxorubicin loaded samples achieved death of >85% of the cancer cells.