(168c) Preparation of Organic-Inorganic Hybrid Microcapsules with Carboxymethyl Cellulose and Aminosilane Hybrid Shell Aimed for Drug Delivery Application

Microcapsules with core-shell structure have been attracting attention as carriers for drug delivery systems because the properties of microcapsules can be tuned by proper selection of the shell constituents according to the needs of biomedical applications. Layer-by-layer (LbL) technique is recognized as the most promising approach to design and development of drug-loaded microcapsules with tailored different functionalities. In the LbL technique, multilayer shell is elaborated on template micro/nanoparticles through step-wise adsorption of oppositely charged polyelectrolytes. Numerous polyelectrolytes such as synthetic and natural polymers have been used to fabricate diverse multilayer shells with tunable compositions and structures. However, the encapsulation of drugs within polyelectrolyte capsules still presents a significant challenge because of the shell’s high permeability. As a way to overcome this issue, functionalization of polyelectrolyte microcapsules through sol-gel processes using silicon alkoxides and silane coupling agents would be very attractive because of its unique approach to fabricate hybrid microcapsules with novel physicochemical features, including a low permeability and intracellular degradability. However, only few examples were reported for fabricating organic-inorganic hybrid microcapsules without use of organic solvents and catalysts. Therefore, there is still room to explore potential combination of polyelectrolytes and inorganics to meet the demands for a variety of biomedical applications. Herein, we proposed a facile approach to fabricate hollow microcapsules with organic-inorganic hybrid shells consisting of carboxymethylcellulose (CMC) as an anionic polymer and aminoethylaminopropyltrimethoxysilane (AAPTS) as a cationic shell component.

In a typical experiment, calcium carbonate microparticles doped with CMC, abbreviated as CaCO₃(CMC), were synthesized by mixing equivalent volumes of 0.02M CaCl₂ and 0.02M Na₂CO₃ solutions in the presence of 0.05% CMC. After 10 min of mixing, the CaCO₃(CMC) microparticles were centrifuged, washed with distilled water. Then, consecutive adsorption of CMC and AAPTS on the CaCO₃(CMC) was performed by incubating the particles in CMCNa or AAPTS solution for 15 min, 1 hour respectively. After that, the CaCO₃ core was dissolved using 0.1M EDTA solution.

Optical microscope observation confirmed that the hollow capsules with a diameter of 2 to 5 µm were successfully fabricated by this method. In the absence of CMCNa or AAPTS, the formation of the hybrid capsules after dissolving the core particles treated with EDTA solution was not confirmed, demonstrating that both CMCNa and AAPTS were essential constituents to fabricate the hybrid capsules. The influence of pH in CMCNa and AAPTS solutions on morphologies and formation yield of the hybrid capsule suggested that the complex formation of CMCNa and AAPTS on the surface of CaCO₃ particles might be achieved via electrostatic attraction between negatively charged carboxylate groups of CMCNa and positively charged amino groups of AAPTS. Preliminary experiments suggested that the capsule formation was affected by concentrations of CMCNa and AAPTS, duration time, layer number and pH conditions. Other combination such as alginate and AAPTS, and application of these hybrid capsules for drug delivery are now under investigation.