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Abstract

Objectives: Development of a novel method for loading drugs into spherical mesoporous silicate nanoparticles (MSNs), and further modification for the loaded MSNs to produce smart drug delivery system. Methods: MSNs have been prepared and loaded using rotary evaporation as a novel method for drug loading. The highly loaded MSNs were further modified as a smart drug delivery system designed for endosomal escape, and sustained release of its cargo into the cytosol. MSNs loaded with anti-tuberculosis front line drugs such as isoniazid, pyrazinamide, pyrazonic acid, and ethambutol, in addition to fluorescein, have been coated with polyethyleneimine followed by mannose labeling for selective targeting of macrophage cells, the loading efficiency was compared to the conventional impregnation loading method. The selected drugs exhibit differences size, charge, and polarity. The developed delivery system has been characterized to indicate the surface are, loading efficiency, morphology, and release behavior at different pH. Results: The loading process is independent of the nature of the drug molecule used and achieves loading efficiencies reaching one order of magnitude higher than those reported for conventional impregnation loading method. Characterization of the modified system indicated unique high surface area as high as 875.8 m2/g, pore size of 3.86 nm, and total pore volume of 1.029 cm3/g. In-vitro release experiments confirmed the pH-controlled release of the cargo molecules from the nanoparticles. Conclusion: We have concomitantly employed previously reported components such as mesoporous silicate, polyethyleneimine coating and mannose labeling, in addition to a novel encapsulation method combined together to develop a smart drug delivery system making use of the advantages of each component. The developed system may be used as a potential novel drug delivery system for combating tuberculosis and/or alike clinical disorders.