Thirawong Nartaya, Thongborisute Jringjai, Takeuchi Hirofumi, Sriamornsak Pornsak
Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000 Thailand.
J Control Release. 2008 Feb 11;125(3):236-45. doi: 10.1016/j.jconrel.2007.10.023. Epub 2007 Nov 4.
Self-assembling pectin-liposome nanocomplexes (PLNs) were prepared by a simple mixing of cationic liposomes with pectin solution, in order to improve intestinal absorption of calcitonin (eCT). Both in-vitro and in-vivo evaluations for PLNs were evaluated. The results showed that average particle size of PLNs was significantly larger than that of initial cationic liposomes. The surface charges were shifted from positive to negative after mixing with pectin. The PLNs made of high degree of esterification (DE) pectin showed less negatively charged values than those made of low DE pectin. The entrapment efficiency in cationic liposomes was in the same range even if the drug loading was increased. The in-vivo mucoadhesive test of pectin by confocal laser scanning microscopy demonstrated stronger mucoadhesive properties of PLNs made of low DE pectin, compared to cationic liposomes and PLNs made of other pectins. Moreover, high intensities of a fluorescent marker could be observed throughout the small intestines (i.e. duodenum, jejunum and ileum) and remained at the site of mucoadhesion even after 6 h of administration of PLNs made of low DE pectin. The eCT-loaded PLNs demonstrated a strong pharmacological action over the eCT solution and eCT-loaded liposomes, in which an enhanced and prolonged reduction in plasma calcium concentration of rats was observed. This was attributed to the ability of pectin to adhere to the mucus layer and prolong retention in the intestinal mucosa.
通过将阳离子脂质体与果胶溶液简单混合制备了自组装果胶-脂质体纳米复合物（PLNs），以提高降钙素（eCT）的肠道吸收。对PLNs进行了体外和体内评估。结果表明，PLNs的平均粒径明显大于初始阳离子脂质体。与果胶混合后，表面电荷从正变为负。由高酯化度（DE）果胶制成的PLNs的负电荷值低于由低DE果胶制成的PLNs。即使增加药物负载量，阳离子脂质体中的包封率仍在相同范围内。通过共聚焦激光扫描显微镜对果胶进行的体内黏膜黏附试验表明，与阳离子脂质体和由其他果胶制成的PLNs相比，由低DE果胶制成的PLNs具有更强的黏膜黏附特性。此外，在整个小肠（即十二指肠、空肠和回肠）中都可以观察到荧光标记物的高强度，并且在给予由低DE果胶制成的PLNs 6小时后，荧光标记物仍保留在黏膜黏附部位。负载eCT的PLNs对eCT溶液和负载eCT的脂质体表现出强大的药理作用，其中观察到大鼠血浆钙浓度有增强和延长的降低。这归因于果胶粘附于黏液层并延长在肠黏膜中保留时间的能力。
