Preparation And Properties Of Microcapsules Templated On Removable Cores For Photodvnamic Therapy

Photodynamic therapy is a new method to cure cancer specifically through combining of laser and photosensitizer. Under laser, photosensitizer makes surrounding O2change to singlet oxygen etc., which kills cells through oxidation of biological macromolecules. However, the singlet oxygen which plays a major role in killing cells can exist for short time. Hence it is promising to achieve the photosensitizer delivery in site. One feasible way is to deliver photosensitizer with carriers. Hollow microcapsules have been widely used in pharmaceutical, biotechnology and catalysis, and synthetic chemistry because both the wall and the cavity can load functional substances. There are many traditional ways to prepare hollow microcapsules, such as spray drying, polymerization, and phase separation. Recently, the sacrificial template method has been widely used for preparing hollow microcapsules, and their size, wall thickness and composition can be pre-designed and easily controlled. More important, the capsules can be easily functionalized.In this paper, the (PDADMAC/PSS)5capsules with PSS loaded were fabricated on PSS doped CaCO3particles by a layer by layer assembly method, following by core removal. Water-soluble photosensitizer methylene blue (MB) molecules with low molecule weight and positive charges were deposited into the capsules through electrostatic interaction between PSS and MB, and then they were trapped within capsules through capsules shrinkage after30min heat treatment in80℃water bath. In biological systems, MB is easily reduced to the colorless methylene blue without photodynamic activity. The release profile of MB from capsules was studied in PBS (pH7.4). The MB molecules could be well preserved inside the capsules for long time, and the capsules could protect MB against enzyme reduction. The in vitro cell culture experiment proved that the loaded MB had a significant phototoxicity to HeLa cell under light activition, which showed great photodynamic effect.Chitosan (CS) is one kind of polysaccharides with good biocompatibility, molecular chain with lots of amino-groups, non-toxic to human body, antibacterial and anti-inflammatory effects. Chitosan capsules with micron-size wall were fabricated by incubating CaCO3microparticles in CS solution at pH5.2and following with ethylenediaminetetraacetic acid disodium salt (EDTA) treatment. Repeating the incubation caused stepwise increase of wall thickness and finally resulted in CS microcapsules with a layered structure. For studying the formation mechanism of the microcapsules with such a special structure, we studied the dissolution amount of CaCO3and the pH change of solution after incubation in CS solution. The obtained CS capsules were stable at physiological condition without any cross-linking. The hydrophobic fluorescent dye Coumarin6and photosensitizer zinc phthalocyanine (ZnPc) as model drugs were loaded onto the wall of CS capsules, showing that the micron-size wall could enrich the hydrophobic drugs with high concentration. Functional nano-gold particles were also synthesized in the wall through in-situ reduction by amino groups. The in vitro cell culture experiment showed that the loaded ZnPc had a significant phototoxicity to HepG2cell under light activition, but the capsules with ZnPc loaded showed dark toxicity in some extent.