In vitro release and degradation of poly(ethyl 2-cyanoacrylate) nanocapsules prepared from w/o microemulsion

• Main Authors: Chia-chen Hsu, 許家禎
• Other Authors: 高純琇
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/59544975041975050831

碩士 === 國立臺灣大學 === 藥學研究所 === 92 === Poly (alkyl cyanoacrylate) (PACA) nanoparticles have gained extensive interest as drug carriers because of the biocompatibility and biodegradability of the polymer and the simplicity of the polymerization process. Microemulsions are thermodynamically stable systems and can be formed spontaneously when properly formulated. Nanocapsules can be prepared by interfacial polymerization of water-in-oil microemulsions. In the previous study, poly (ethyl 2-cyanoacrylate) (PECA) nanocapsules were successfully prepared by adding ECA monomers into a water-in-oil microemulsion system, which was composed of toluene, water and sodium bis (2-ethylhexyl) phosphate (NaDEHP) as the surfactant. After polymerization, evaporation under reduced pressure was used to the purification of nanocapsules. The aim of present study is to study the effects of monomer concentration and monomer mass adding to polymerization on the encapsulation efficiency. Furthermore, the effects of pH, formulation variables and esterase on the release profiles of degradation products (formaldehyde and ethanol) and drugs are also investigated. Particle size of nanocapsules suspended in reaction media were measured by dynamic light scattering (DLS), which were significantly higher than the particle size of PECA nanocapsules purification by scanning electron microscopy (SEM). This may be due to the shrinking effect after the process of nanocapsule purification. The efficiency of nicardipine HCl entrapment within PECA nanocapsules was influenced by the concentration of monomer solution and the mass of monomer used in the polymerization. The monomer solution of lower concentration and the increase of monomer mass resulted in higher drug encapsulation efficiency. The PECA nanocapsule degradation study showed that the polymer would degrade faster in higher pH phosphate buffer solution (PBS). The degradation of polymer was faster in formulation 1(the volume ratio of monomer added to water phase 1:20) as compared with formulation 2 (the volume ratio of monomer added to water phase 1:10). The enzymatic degradation of PECA by esterase increased the production of ethanol but decreased the production of formaldehyde. The drug release study of nicardipine HCl nanocapsule also showed that the two formulations provided products with a potential for controlling the drug release. Drug release rate was faster in higher pH PBS. After 168 hours, there was no significant difference in total release % of the three groups (pH 3.0, 7.4 and 9.0) in formulation 1 (about 85%). However, the release of nicardipine HCl was suppressed under basic conditions (pH 9.0) in formulation 2. The existence of drug-polymer interactions may lead to some of the drug remaining in the nanocapsules, and drug can not completely release. Formulation 1 had a faster drug release rate then formulation 2 may also attribute to the less tightness of polymer wall. When PECA nanocapsules were exposed to esterase, the drug release pattern would be changed.