Functionalized Hollow Mesoporous Silica Nanospheres for drug delivery

Jomehfarsangi, Zohreh (School of Advanced Technologies in Medicine, Tehran University of Medical Sciences)
Hatton, Benjamin D (University of Toronto)
Beitollahi, Ali (Iran University of Science and Technology)
Jafari, Mahmoudreza (Department of Pharmaceutics, Mashhad University of Medical Sciences)

Introduction

Nanomedicine attempts to enhance the bioavailability of drugs and to reduce their side effects. Creation of functional hollow mesoporous naospheres (HMNs) could be desirable for biomedical applications since their hollow interior can be used as storage or nanoscale reactor while mesoporous shell providing the controlled uptake/release role. Functionalization of the internal surface of the pores with several organic molecules regulate the interactions between the drug and hollow space that can selectively and efficiently accommodate more drug molecules. Herein we used a hard templating method to fabricate HMCs of good flexibility on shape and size of the hollow cavity and mesoporous shell and vast feasibility for further functionalization that can offer controlled release and targeted delivery.

Materials and Methods

The polystyrene latex with the size of 70 nm was prepared through emulsion polymerization. In a round-bottom flask, 90 g deionized water; 0.3 g SDS and 0.1 g sodium bicarbonate were added and kept stirring at 800 rpm for 30 min under the nitrogen flow. Then 9.0 g styrene was added to the mixture purged with nitrogen for 15 min before heating to 70ᵒC. Afterwards, 1 ml of an aqueous solution containing 0.1 g KPS was added. The emulsion was kept at 70ᵒC for 24 h under nitrogen to allow the polymerization to complete. The HMNs with the size of 100 nm were then prepared. Typically, 0.35 g of CTAB was dissolved in a mixture of 15.0 g H2O, 6.0 g ethanol and 0.250 ml ammonium hydroxide. After 30 min stirring 5.0 g of PS-70 was added drop-wise to the above CTAB solution at room temperature under vigorous stirring, followed by sonication for 15 min and magnetically stirring for 30 min before drop-wise adding of 1.5 g TEOS. The mixture was kept at room temperature for 48 h and the mesoporous silica coated polystyrene was harvested by centrifugation, washed with ethanol for three times before drying at 80ᵒC for overnight. The latex core and CTAB template were dissolved through reflux in THF with at 70ᵒC for 24 h. Carboxyethylsilanetriol as a silane coupling agent was used for functionalization of the internal surfaces with carboxyl groups. The microstructure of the synthesized HMNs was characterized by field-emission scanning electron microscope (FE-SEM) and transmission electron microscope (TEM) to measure size and analyse morphology. The surface area and pore size were obtained by using Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH). The FTIR analysis was performed to confirm the complete removal of the template and successful functionalization with carboxyl groups.

Results

The hollow interior was formed after removal of the polystyrene by dissolution. The FESEM images indicate spherical morphology with a uniform diameter of 100 nm and the contrast between the dark edge and clear center confirms the formation of hollow cavity. After dissolution the HMNs still retain the same morphology as before with a good colloidal stability. According to the obtained BET results the surface area of HMNs was about 1200m3/g and the pore size was about 2 nm. The FTIR spectra show the complete removal of the CTAB and polystyrene core and also emphasize the presence of the carboxyl groups.

Discussion and Conclusion

Hollow mesoporous silica nanospheres with excellent biocompatibility, high surface area and a central cavity have several advantages as drug delivery vehicles. By used method the particles size and shape are easily tunable. The huge surface area and pore volume allows for a high drug loading. Modified pores can have an efficient control on drug uptake and release. Further, surface engineering may offer targeted delivery and facilitate bioavailability and cellular uptake. Next steps will include the drug loading and release analysis.



References

1-Veronika Mamaeva, Cecilia Sahlgren, Mika Lindén, , Mesoporous silica nanoparticles in medicine—Recent advances, Advanced Drug Delivery Reviews 65(2013) 689-702 2-Yu Chen, Hangrong Chen, and Jianlin Shi, Engineering of Hollow Mesoporous Nanoparticles for Biomedical Applications Advanced Porous Materials, Vol. 1, 34–62, 2013

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