Based On The Preparation Of Mesoporous Silica Composite Nanoparticles, Performance And Drug Controlled Release

The development of new nanomaterials for the diagnosis and/or treatment of different diseases has been receiving greater attention in recent years and has now become an important field in medical research. Dedicated nanomaterials can be used to monitor the progress of a therapy or disease, to determine the blood type of patients requiring transfusion, or for tissue typing when a transplant is required. The following unique properties of MSNs, such as tunable particle size, stable and rigid framework, uniform and tunable pore size, high surface area and large pore volume, two functional surfaces, unique porous structure and biocompatibility, have attracted a lot of research attention for various controlled release delivery applications.As outlined below, several perquisites need to be incorporated into such a material in order to serve as efficient drug delivery systems.(1) The carrier material should be biocompatible.(2) High loading/encapsulation of desired drug molecules.(3) Zero premature release of drug molecules.(4) Controlled release of drug molecules with a proper rate of release to achieve an effective local concentration. Based on the MSNs, several nano-sized drug carriers with uniform diameters were synthesized. A diversity of surface modification was subjected to systematic investigation using organic silanes, in order to study the drug loading capacity and sustained release behaviour of the modified M-MSNs for representative drugs. The polymer coated MSNs systems were used as "gatekeepers" to regulate the encapsulation and release of drug molecules. The main results were listed as follows:(1) A general and facile strategy was developed to coat hydrophilic nanoparticles directly with mesoporous silica nanoparticles (MSNs). The cationic surfactant of cetyltrimethylammonium bromide (CTAB) was adsorbed to various hydrophobic or hydrophilic inorganic nanoparticles, introducing the CTAB layer overcoating with positive charge. The subsequent sol-gel reaction of TEOS with the basic catalyst resulted in uniform nanocomposites. The relatively high CTAB concentration and proper pH value in the initial reaction system were the key factors for synthesizing uniform, colloidal nanocomposites with obvious core/shell-structure. The controlled preparation method of multifunctional silica nanocomposites provided the platform for designing multifunctional MSNs to assess biological effects.(2) The keystone in the development of MSNs as drug carriers is the modification or functionalization of the surface through organic groups. This process provides numerous possibilities to control drug adsorption and release. A diversity of surface modification was subjected to systematic investigation using organic silanes, eventually resulting in the decoration with the carboxyl (-COOH), methyl phosphonate (-PO3-), amino (-NH2) and phenyl (-Ph) groups on the surface of MSNs. The hydrophilically modified MSNs with-COOH and-PO3-were beneficial for loading the water-soluble doxorubicin hydrochloride (DOX) through electrostatic attraction. The results demonstrated that MSNs-PO3-achieved a higher loading content and MSNs-COOH presented a distinct pH-responsible release behavior. On the other hand, MSNs-Ph displayed a controlled release rate in a short term via the weakened hydrogen bonding interaction.(3) A kind of core-shell composite nanosphere was prepared based on poly(N-iso propylacrylamide-co-methacrylic acid) coated magnetic MSNs via precipitation polymerization. The composite nanoparticles presented a thermo/pH-coupling sensitivity and the volume phase transition could be precisely regulated by the molar ratio of MAA to NIP AM or the concentration of NaCl. At physiological conditions (37℃,0.15M NaCl), the P(NIPAM-co-MAA) shell underwent a distinct transition from a swollen state in pH7.4to a collapsed state in pH5.0, so that the polymer shell was active in moderating the diffusion of embedded drugs in-and-out of the pore channels of MSNs. DOX was applied as a model drug and the behaviors of drug storage/release were investigated. The drug loaded behavior was pH-dependent, and the composite nanoparticles had a drug embed efficiency of about91.3%under alkaline condition. The cumulative in vitro release of the DOX-loaded nanocomposite showed a low level of leakage below the volume phase transition temperature (VPTT) and was significantly enhanced above its VPTT, exhibiting an apparent thermo/pH-response controlled drug release. The cytotoxicity assay of a blank carrier to normal cells indicated that the composite microspheres were suitable as drug carriers, while the DOX-loaded composite microspheres had a similar cytotoxicity to HeLa cells compared with free DOX.(4) The nanocomposites was prepared with-COOH modified MSNs as core and poly(N-vinylcaprolactam-s-s-methacrylic acid)(P(VCL-s-s-MAA)) as shell, which comprised a polyethylene glycol (PEG) corona to stabilize the particles and the N,N’-bis (acryloyl) cystamine as a reversible cross-linker, while the mesostructure of the core was completely retained. The obtained core-shell nanospheres presented both temperature and pH sensitivity. The thermo-sensitive volume phase transition could be precisely regulated by the mass ratios of MAA to VCL. An increase in the pH value led to a significant increase in VPTT, which can be adjusted as desired close to human body temperature (37℃). The composite nanospheres, though sufficiently stable in water, were prone to fast disappearance for polymer shell in the presence of10mM glutathione (GSH), due to shedding of the reductive cleavage of the intermediate disulfide bonds in P(VCL-s-s-MAA) polymer shell. DOX was also applied as a model drug to evaluate the loading and release properties. Drug leakage can be avoided in MSNs@P(VCL-s-s-MAA) storage and significantly reduced in blood circulation, whereas a burst release of drug was triggered in an acidic and reductant-enriched environment such as in lysosomes. Therefore, the thermo/pH-sensitive nanocomposites with reductively sheddable polymer shell gate could, in principle, be used for in vivo cancer therapy with a low premature drug release during blood circulation whilst having a rapid release upon reaching tumor tissues.