The Preparation And Modification Of Composite Hollow Spheres And Their Application In Controlled Release

Inorganic hollow spheres are promising for controlled and sustained drug release applications due to their characteristics such as high structure stability, controlled morphologies, adjustable pore size, facile surface modification. Recently, more and more research groups have reported drug delivery vehicles based on hollow spheres with single shell material. However, the desirable loading, storage and release environment of various drugs is widely divergent from each other. Obviously, single shell spheres, even if a modification is processed, could hardly meet the complicated demands, since it has only one shell and as a result every modification takes place on the whole shell. Therefore, hollow and core-shell spheres with composite structure, which have advantages in selective modification due to their distinctive properties of inner and outer materials, are synthesized in this paper. Herein, their drug loading amounts and release behaviors, for both unmodified and modified systems have been investigated.1. Using spherical P(St-co-AA) particles as templates, TiO2/SiO2 composite hollow spheres(CHSs) have been successfully synthesized via sol-gel method. Their hollow and porous structures were confirmed by transmission electron microscope (TEM) and N2 sorption analysis. Furthermore, they are highly intact and have suitable pore size distribution.2. The inner layers of the CHSs were selectively modified with stearic acid and phosphate. Using water-insoluble ibuprofen (IBU) as a model drug, the investigation of drug loading amounts and release rates of the CHSs shows that they can be regulated by suitable modification. Compare with the unmodified system, the stearic acid modified CHSs exhibit higher drug loading amount(189.8 mg/g) and lower release rate due to the hydrophobic effect. However, the phosphate modified CHSs exhibit relatively low drug loading amount (153.5 mg/g) and increased release rate, probably associated to the hydrophilic shell and charge repulsion.3. TiO2 can facilely form stable hydrophobic layers by Lewis acid-base interaction with phosphatidylcholine(PC). The CHSs were selectively modified with PC. Studies demonstrate that, due to the introduction of the hydrophobic chains, the system shows higher drug loading amount and lower release rate than that of the unmodified system. More importantly, when modified with high concentration of PC in the existence of cholesterol, the release rate of the system decreased further, it could attribute to the formation of liposome vesicles in the cavities and pore channels.4. For further study the effect of the selective modification on drug release, CaCO3/SiO2 core-shell spheres have been synthesized. Using water-insoluble ibuprofen and water-soluble propranolol hydrochloride as two kinds of model drugs, the investigation of drug release rates for the CaCO3/SiO2 core-shell spheres shows that they can be regulated by suitable modification. For ibuprofen, the phosphate modified spheres (NaP-CaCO3/SiO2) exhibit the fastest release rate due to the charge repulsion, whereas the unmodified spheres(CaCO3/SiO2) exhibit the slowest release rate due to the chemical adsorption between COO- and CaCO3. For propranolol hydrochloride, NaP-CaCO3/SiO2 system shows the best sustained release behavior, attributed to the chemical adsorption between-NH and PO43-, whereas the unmodified system underwent the fastest release stage. In addition, the stearic acid modified interior can serve as smart nanophase extractor to capture and concentrate organic drug molecules from the aqueous release medium. Since hydrophobic effect is weaker than chemical adsorption, the stearic acid modified system shows sustained release behavior between CaCO3/SiO2 and NaP-CaCO3/SiO2.Composite hollow and core-shell spheres have distinct inner and outer surface that can be modified differently depending on their roles to obtain adjustable drug loading amounts and release rates, drug-friendly interiors and environment-friendly exteriors. Therefore, they are potential for drug delivery applications.