Mesoporous materials have various addition methods in the field of high - efficiency drug delivery, aiming to achieve effective drug loading, precise delivery, and controlled release:
I. Direct Loading of Drugs as Drug Carriers
1.1 Direct Drug Loading (Physical Adsorption Method)
Mesoporous materials, with their unique pore structures and large specific surface areas, provide ample storage space for drug molecules. Take mesoporous silica nanoparticles (MSNs) as an example. Their specific surface area can reach 500 - 1500 m²/g, and the pore size can be precisely adjusted between 2 - 50 nm. Disperse MSNs in an ethanol solution of doxorubicin and continuously stir at 37 °C for 12 hours. Due to the capillary action and surface adsorption force of the mesopores, doxorubicin molecules are uniformly filled into the pores of MSNs through physical adsorption. Research shows that the drug - loading rate of this direct drug - loading method can reach up to 40% (mass fraction), and the activity of the drug is hardly affected during the loading process. In addition, by adjusting the concentration of the doxorubicin solution and the loading time, the drug - loading amount can be flexibly controlled. When the concentration of the doxorubicin solution increases from 0.5 mg/mL to 2 mg/mL, the drug - loading amount increases from 15% to 35%.
Mesoporous materials have a high specific surface area and rich pore structures, enabling them to load drugs through physical adsorption. The mesoporous materials are directly added to the drug solution, and under appropriate conditions of temperature, stirring speed, and time, the drug molecules spontaneously enter the pores of the mesoporous materials to achieve loading. For example, when mesoporous silica nanoparticles are added to an aqueous solution of the anticancer drug doxorubicin and stirred at room temperature for several hours, doxorubicin can be filled into the pores of mesoporous silica through physical adsorption. This method is simple to operate and has little impact on the chemical structure of the drug.
1.2 Impregnation Method
The mesoporous materials are immersed in a high - concentration drug solution, allowing the drug solution to fully penetrate into the pores of the mesoporous materials. Subsequently, the solvent is evaporated to leave the drug in the pores and complete the loading. For example, when preparing mesoporous materials loaded with ibuprofen, the mesoporous materials are placed in an ethanol solution of ibuprofen. After long - term impregnation, the ethanol is evaporated, and ibuprofen is loaded onto the mesoporous materials.
A Preparation Method and Process of Ibuprofen Capsules
II. Loading Drugs after Modification
To achieve precise drug delivery, surface modification of mesoporous materials is a crucial step. Folic acid is modified on the surface of mesoporous carbon nanospheres for loading paclitaxel. First, the mesoporous carbon nanospheres are aminated using 3 - aminopropyltriethoxysilane (APTES), making the surface rich in amino groups. Then, through the coupling reaction mediated by 1 - ethyl - 3 - (3 - dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N - hydroxysuccinimide (NHS), folic acid molecules are covalently linked to the surface of the aminated mesoporous carbon nanospheres. The grafting rate of folic acid on the modified mesoporous carbon nanospheres can reach 5 - 10 μmol of folic acid per gram of material. When loading paclitaxel, oscillate in a phosphate - buffered saline (PBS) solution with a pH of 7.4 at 37 °C for 24 hours, and the drug - loading amount can reach 25% - 30%. Experiments show that the uptake of the modified drug - loading system by tumor cells expressing folic acid receptors is 3 - 5 times higher than that of the unmodified system, significantly enhancing the targeting of drug delivery and reducing the toxic side effects on normal tissues.
2.1 Surface Functionalization Modification
To increase the drug - loading capacity of mesoporous materials, improve the drug - release behavior, or impart targeting properties to the materials, the surfaces of mesoporous materials are often functionalized. First, the surface of the mesoporous material is modified with specific chemical reagents to introduce active groups, such as amino groups (-NH₂), carboxyl groups (-COOH), etc. Then, these active groups react chemically with drug molecules to achieve covalent attachment of the drug. For example, the mesoporous material with amino groups is linked to the drug containing carboxyl groups through a condensation reaction. Compared with physical adsorption, this covalent attachment method enables the drug to be more stably loaded on the mesoporous material, and the drug - loading amount can be precisely controlled by controlling the chemical reaction conditions.
2.2 Modification by Introducing Targeting Groups
To enable the drug to reach the diseased site precisely, targeting groups can be introduced onto the surface of mesoporous materials. Molecules with targeting functions, such as antibodies, peptides, aptamers, etc., are linked to the surface of mesoporous materials through chemical coupling. For example, in cancer treatment, antibodies against specific antigens on the surface of tumor cells are modified on the surface of mesoporous materials. After loading the drug, the mesoporous material - drug complex can specifically recognize and accumulate around tumor cells, increasing the concentration of the drug at the diseased site and reducing side effects on normal tissues.
III. Construction of Composite Systems
Combining mesoporous materials with other functional materials can endow the drug - delivery system with more functions. Mesoporous titanium dioxide is combined with liposomes to encapsulate photosensitive drugs. First, mesoporous titanium dioxide is prepared by the sol - gel method, with an average pore size of approximately 10 nm and a specific surface area of approximately 300 m²/g. Then, liposomes are prepared by the thin - film hydration method. The liposome solution is mixed with mesoporous titanium dioxide, and under ultrasonic conditions, the liposomes uniformly coat the surface of mesoporous titanium dioxide. The encapsulation efficiency of this composite system for photosensitive drugs can reach over 80%. Under near - infrared light irradiation, the photosensitive drug on the surface of mesoporous titanium dioxide is activated to generate singlet oxygen. At the same time, the liposomes enhance the penetration ability of the composite system into the cell membrane, achieving a synergistic effect of light - responsive and high - efficiency drug delivery, effectively killing tumor cells.
Characterization and Application of Mesoporous Titanium Dioxide Thin Films Prepared by Sol - Gel Method
3.1 Composite with Polymers
Combining mesoporous materials with polymers to form composites can integrate the advantages of both and improve drug - delivery performance. One method is to coat the mesoporous material surface with a polymer to form a core - shell structure. For example, using mesoporous silica as the core, a poly(lactic acid) (PLA) polymer shell is coated on its surface through emulsion polymerization. The drug is loaded in the pores of mesoporous silica, and the PLA shell can protect the drug and control the drug - release rate. Another method is to uniformly disperse the mesoporous materials in the polymer matrix to form a blend system, jointly achieving drug loading and delivery.
3.2 Composite with Magnetic Materials
Magnetic mesoporous composites are prepared to combine magnetic responsiveness and drug - loading capacity. Magnetic nanoparticles (such as iron oxide nanoparticles) are combined with mesoporous materials through physical mixing or chemical synthesis. Under the guidance of an external magnetic field, the magnetic mesoporous composite can move directionally to the target site, achieving targeted drug delivery. For example, in cancer treatment, an external magnetic field is used to guide the magnetic mesoporous composite loaded with anticancer drugs to the tumor tissue, improving the drug treatment effect.
Iron(III) oxide/ Magnetic nanoparticles/ Magnetic resonance contrast agents
3.3 Multilayer Drug Loading
Multilayer drug loading is carried out in the pores of mesoporous materials to achieve sequential or synergistic release of different drugs. For example, a fast - releasing emergency drug is first loaded in the inner layer of the mesoporous pores, and a long - acting therapeutic drug is loaded in the outer layer. By controlling the interaction strength between each layer of drug and the mesoporous surface, different release rates can be achieved. This method can be used to treat complex diseases, such as emergency treatment and subsequent rehabilitation of cardiovascular diseases.
