Surface Functionalization Of Bimodal Mesopores Silicas And The Application In Drug Delivery

Controlled drug-delivery systems, a kind of drug-delivery systems which could release drug slowly in water or specific medium, because of its advantage such as reducing administration, improving patients compliance, keeping stable and effective plasma concentration, enhancing the drug safety and effect, and reducing drug side effects on the gastrointestinal tract, have received more and more attention. The initial controlled drug-delivery systems were non-degradable, and then were substituted by biodegradable polymers. Recently, with the development of nano-technology, lots of organic nano-materials have been studied as drug carriers. Although the advantages of biodegradable nano-materials are undoubted, more and more researches have been focusing on the applications of inorganic nano-materials in the research field of controlled drug delivery in recent years, due to the obvious shortcoming such as poor chemical stability, difficult control over the release rate and imperfect compatibility,. With the appearance of the mesoporous materials M41S, the scientist realized that this new kind of inorganic porous materials could overcome the weaknesses mentioned above, and become one of the excellent carriers. Since the first report from Spanish professor Vallet-Regíof the application of MCM-41 as ibuprofen carrier, mesoporous nano-materials occupied important position in the research of controlled drug delivery because of its excellent features, for example, the adequate silanols on the inner surface could provide adequate active sites for drug molecules; the tuneable porous channels could be designed for different drug molecules, and also the ideal biocompatibility and safety compared with other nano-materials. Bimodal mesoporous material (BMMs) is a new mesoporous material consisting of worm-like mesopores of 3nm as well as large inter-particles pores around 10-30 nm. Different from mesoporous materials with only one pore distribution, BMMs could realize the loading and controlled release of specific drug molecules, especially for the insoluble drugs, through surface modification, due to the unique characteristics such as the controllable structure and particles size. In comparison with MCM-41 and SBA-15, BMMs could also achieve controlled delivery of many kinds of drug in simulated body environment, and therefore could serve as a benign drug carrier.BMMs have been synthesized and through modifying the mesoporous surface with two silane coupling agent, 3-(2-aminoethylamino)propyltrimethoxysilane and 3-aminopropyltriethoxysilane, were used as carriers of three drug, aspirin, ibuprofen and taxol, with increasing molecular size and reducing solubility, to explore the feasibility of BMMs as different drug carriers. And at the same time MCM-41 and SBA-15 were also synthesized as comparison to study the influence of mesoporous structure, superficial properties and release medium on the controlled release mechanism of drug molecules with different size and solubility. The drug release profiles were fitted with Korsmeyer–Peppas model to obtain the release kinetic constant k. Meanwhile, combined with the density function theory (DFT), the surface energy distributions (SEDs) of samples including before and after modification and drug loading were studied. Besides with Flynn-Wall-Ozawa and Kissinger methods, the apparent activation energies (Ea) were studied during the superficial amino modification and drug adsorption to explore the existence state of the functional groups and drug molecules in the mesoporous channels, and the influence factors and controlling mechanism of mesoporous materials on drug delivery will be obtained.Firstly for aspirin, a kind of drug with small molecular size and low solubility, BMMs could achieve good controlled release performance with a large drug loading amount based on its bimodal mesoporous structure, although the loading amount was less than SBA-15 with larger mesoporous channels. By changing the types and quantities of superficial functional groups, the surface energy of BMMs would increase which was good for the interaction with aspirin molecules and finally achieved higher drug loading amounts Therefore, choosing various mesoporous materials with different mesoporous structure and functional groups to modify the mesoporous surface is an effective way for controlled drug adsorption and release. Based on the conclusion mentioned above, for ibuprofen with poor solubility, because of the relatively large molecular size obstructing the multilayer physical adsorption, the drug loading amounts of BMMs was more than that of SBA-15. Meanwhile by changing the particle size, BMMs with different inter-particle pores were applied as ibuprofen carrier, and the results demonstrated that the functional groups and drug molecules were introduced into the mesopore around 3 nm, while the inter-particles pores would influence the drug diffusion behaviour in the mesoporous channels directly. Hence the drug release rate could be accelerated by increasing the particles size of BMMs. Besides, based on the interaction between the drug molecules and superficial groups, the desorbed ibuprofen molecular existed in ionic states, so water was better release medium for ionic ibuprofen compared with simulated body fluid and simulated gastric fluid. On the contrary, because of the low solubility of ibuprofen molecules in water, the release process will be obstructed in acid simulated gastric fluid and result in low release percentage. These phenomena indicate that the pH value and composition of release medium would also affect the drug release profiles.When BMMs was used as the carrier for natural product taxol, the taxol would be mainly adsorbed at the pore opening of BMMs because of their very large molecular size and insolubility, which means the pore size of mesoporous materials will also determines the size of the molecular besides the effect on the drug diffusion. On the other hand, when mesoporous surface was grafted with polar groups, the loading amount of taxol decreased obviously, because of the weak polarity of taxol molecular. This result further verifies that the interaction between the drug molecules and superficial organic groups is an important factor to obtain large drug loaded amounts. Besides, the release behaviour of Taxol/BMMs delivery system was explored preliminarily, and the results confirmed the BMMs is a potential taxol carrier with the successful release of taxol, however the characteristic of taxol after release and controlled release behaviour should be further studied in the future.All the mesoporous materials before and after modification, and related drug loaded samples were characterized by means of X-ray diffraction, scanning electron microscopy, transmission electron microscopy, N2 adsorption-desorption, thermogravimetric analyses, 29Si NMR, Elemental analysis, Fourier transform-infrared spectroscopy and UV-vis spectra.The drug loading and controlled release modal based on the research mentioned have supplied reliable experimental foundation for the practical application of mesoporous nano-materials. With the help of the density function theory and the thermal decomposition kinetics analysis, the function mechanism of mesoporous materials as drug carriers was explored and discussed at the micro-level.