Investigations on the formulation and drug loading features of silica nanoparticles from agricultural biomass

Abstract

Application of nanoparticles as drug carriers in chemotherapy has gained much importance over the past few years for its ability to carry the payload to the specific site of action, which will greatly reduce drug dosage and frequency of administration. It also reduces toxicity to healthy cells thereby increasing the overall efficiency of the therapy. This study attempted to manufacture amorphous silica nanoparticles from otherwise discarded, yet easily available agricultural waste products, employing facile methods utilizing least toxic reagents and requiring minimal processing steps. The efficiency of silica nanoparticles derived from biogenic sources like rice husk were tested for use as a drug carrier in curcumin and epirubicin based formulations for chemotherapy of cancer. Silica nanoparticles of size ~50 nm was synthesized by pressurized acid leaching and controlled incineration techniques. Physicochemical characterization of these particles was carried out. Drug loading and cytostatic effects of the drug loaded nano-formulation on cervical cancer (HeLa) cells were also studied. Biocompatibility tests indicated high compatibility of these particles to normal human embryonic cell lines (HEK293). Loading the drug on to silica nanoparticles enhanced its cytostatic effect as revealed from MTT assay, enhanced expression of the pro- apoptotic gene (Bax) and the suppression of anti-apoptotic gene (Bcl2).Caspase-3 mediated apoptotic pathways were also modulated. Cancer cells treated with drug loaded nano-formulations also resulted in alterations in its nuclear morphology coupled with generation of ROS and fluctuations in mitochondrial membrane potential. The results obtained from cellular uptake studies as well as antioxidant assays indicated enhancement of the therapeutic efficiency of the drug when loaded onto silica nanoparticles. Studies also showed that drug conjugated to the mesoporous silica nanoparticles derived from agricultural biomass like rice husk could still maintain its activity and that it could enhance drug bioavailability. This study resulted in facilesynthesis of amorphous, mesoporous silica nanoparticles from biogenic sources which would aid in value-addition of underexploited agricultural by-products. Considering its high biocompatibility, these biogenic nanoparticles could find other medical applications, as in tissue engineering, enzyme immobilization, dental and bone implants and fillers. Its unique physical and chemical properties like inertness and stability at higher temperatures makes them useful for non-medical applications as food additives and bulking agents, in cement industry, water purification systems etc. The high biocompatibility of these biogenic silica nanoparticles could make them a least toxic substitute to those synthesized by conventional methods. Further improvements to these biogenic nanoparticles could in future be helpful for substantial reduction in treatment costs for different ailments, especially cancer.