Preparation and evaluation of liposome-mesoporous silica nanoparticles loaded with thymoqinone for drug delivery to mcf-7

Pegah Khosravian,1,*

1. Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord,

Abstract


Introduction

Nanoparticles as drug delivery systems can improve traditional treatment methods. nanoparticles, as drug delivery system, can be delivered therapeutic agents into target cells with increase intracellular drug levels to the required concentration. targeting the delivery of drugs by nanoparticles enhance drug efficiency and improve the bioavailability. mesoporous silica nanoparticles (msns) have some properties such as high drug loading capacity, controllable size and pore, large surface area, high biocompatibility and physical stability which are widely used for drug delivery. msns can load drug efficiently in their tunnels leading to sustained drug release from the pores via hydrogen bonding and drug molecules. therefore, msns are able to intelligently deliver drugs in a targeted site and release in a sustained way. liposome-coated msns is another way to controlled release of the drug in targeted site by liposome rupture in acidic medium of cancer cells.

Methods

Thymoquinone, cetyltrimethylammonium bromide (ctab, 98%), mesitylene, tetraethyl orthosilicate (teos, 99%), phosphatidylcholine>90% (pc) and cholesterol>99% (chol) were purchased from sigma aldrich. all other materials used were of analytical or hplc grade. an aqueous solution of ctab (1.0 g) and naoh (0.28 g) was prepared with 480 ml of deionized water. mesitylene (7 ml) was then added and the solution was stirred for 5 hr at 80°c. after that, teos (5 ml) was introduced drop-wise into the solution, and the mixture was magnetically stirred for another 2 hr at the same temperature. the precipitate was filtered and washed with abundant water and ethanol repeatedly. the surfactant was removed via calcination at 540 ºc for 4 hours. drug loading was carried out by adding 50 mg of dry msn, in 5 ml of thymoquinone solution in acetone. after stirring for 48 h under light sealed conditions, the thymoquinone loaded msns were collected by centrifugation and washed with deionized water. liposomal msns were prepared by thin film hydration method. 25 mg pc and 5 mg chol were dissolved in 8 ml chloroform under probe sonication. followed by removal of solvent in rotary evaporator to form a thin film. for lipid coating, the dried lipid film was rehydrated with 5 ml of 1 mg ml-1 msn particle in pbs ph 7.4 and sonicated for 10 seconds using a probe sonicator. the resultant lipid coated msn particles were used for further studies.

Results

The results showed that the msns were successfully synthesized, having good pay load and ph-sensitive drug release kinetics. the size and morphology of the msns were characterized by sem and the particle size distribution of the nanoparticles was found to be relatively narrow and quite uniform with a good dispersion. the xrd pattern of msns was revealed two-dimensional (2-d) hexagonal (p6mm) symmetry. the mesoporous structure of msns was confirmed by obtained type iv isotherm of bet analysis. the pore size of msns was 3.8 nm. so the larger pore size of msns was successfully obtained by using the mesitylene. the ftir spectra confirmed of msns structure. the strong peaks appeared at around 1080, 950 and 800 cm−1 are due to the stretching vibration of si–o–si, si-oh and si-o, respectively, which are specific peaks of the silica nanoparticles. the cellular investigation on mcf-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of nanoparticles.

Conclusion

Nano drug delivery systems as mesoporous silica nanoparticles (msns) with unique properties have the potential to improve drug efficacy. liposome coated msns showed a high thymoqinone loading capacity and ph sensitivity. the cytotoxicity evaluation showed that the cytotoxicity of nanoparticles increased and more apoptosis and necrosis occurred. totally, the results showed that liposome-msns exhibited enhanced target-directed thymoqinone delivery for breast cancer, which can cause a decrease in dose, raise cytotoxic effects and this allows for a more efficient therapy compared to the conventional formulation of free drugs which makes them promising substances for cancer therapy.

Keywords

Liposome, mesoporous silica nanoparticles, thymoqinone, drug delivery system