Preparation and In-Vitro Release Profiles of Nanocapsules Containing an Aqueous Core

• Main Authors: Li-Hua Chang, 張麗華
• Other Authors: 高純琇
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/30820289139443672531

碩士 === 國立臺灣大學 === 藥學研究所 === 93 === Over the past few decades, development of drug carriers such as nanoparticles has caught a lot of attention. Nanoparticle varies in size from 10 nm to 1000 nm and is the collective name for nanosphere and nanocapsule. Poly (alkyl cyanoacrylate) (PACA) nanocapsules have gained extensive interest as drug carriers because of the biocompatibility and biodegradability of the polymer and the simplicity of the polymerization process. The applications attempted to achieve by these carriers include drug targeting, cancer chemotherapy, gene therapy, ocular and oral drug delivery, etc. Therefore, PACA nanocapsule was considered to be a good candidate for the successful exploitation of the drug carrier. Poly (ethyl 2-cyanoacrylate) (PECA) nanocapsules were prepared by interfacial polymerization of a water-in-oil (w/o) nanodroplet system, composed of water, surfactant mixture (Tween 80/ Span 80, 44/56 w/w) and hexane (8.08:25.25:66.67 w/w). The monomer used was ethyl 2-cyanoacrylate (ECA). After removing the oil phase, surfactant and un-reacted monomer, PECA nanocapsules were then obtained. Yields of the production of PECA nanocapsules were about 90%. Results of FTIR and DSC support that the obtained nanocapsules were mainly the products of PECA polymer. Functional IR peaks from PECA nanocapsule and aminophylline were observed in the IR spectrum of aminophylline-loaded nanocapsule. Interaction may exist between aminophylline and PECA in drug-loaded nanocapsule as indicated by DSC results. The morphology of nanocapsules was spherical in shape as seen by SEM. Particle sizes of the nanocapsules estimated by photographs of SEM were significantly lower than the values determined from DLS. The size of droplet in drug-loaded nanodroplet system was larger than the size of droplet in drug-unloaded nanodroplet system. The size of nanocapsules from formulation A (high monomer mass) was larger than those from formulation B (low monomer mass). This may be due to that the higher the monomer mass, the thicker the PECA polymeric wall surrounding the water core. The encapsulation efficiency of aminophylline-loaded PECA nanocapsules were in the range of 1.81% to 44.67% and 0.38% to 25.05% for formulation A and B at various aminophylline concentrations in aqueous phase respectively. The reason for such low encapsulation most likely is that the unstable w/o nanodroplet systems and the alteration of the pH of inner phase, in which higher pH (pH 3.5~ pH 8.3) observed at high drug concentration of aminophylline (1~15 mg/mL). The polymerization of ECA was too faster to be able to disperse evenly in the system before polymerization occurred and hence, leading to low encapsulation efficiently. The results of drug release study of PECA nanocapsules showed that the obtained nanocapsules exhibited sustained release characteristics. Drug-loaded nanocapsules from formulation B-1 had a faster drug release in all pH conditions (3.0, 7.4 and 9.0) than those from formulation A-1 and A-3. The release rates under 37 ℃ and 0.01 M PBS at different pH were in the order of pH 9.0 > pH 7.4 > pH 3.0 for all nanocapsules. This may partially due to the facts that the high PECA nanocapsules degradation and the high aminophylline solubility in alkaline pH conditions. When fitting the drug release profiles to simple mathematical model, it is suggested that limited step of drug release was drug releasing from PECA nanocapsules.