Ishihara Tsutomu, Takahashi Miyuki, Higaki Megumu, Mizushima Yutaka
DDS Institute, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato, Tokyo 105-8461, Japan.
Int J Pharm. 2009 Jan 5;365(1-2):200-5. doi: 10.1016/j.ijpharm.2008.08.030. Epub 2008 Aug 29.
Solid nanoparticles consisting of biodegradable polymers have emerged as a promising carrier for various drugs, but unfortunately the encapsulation of drugs remains challenging. In this study, a technique for encapsulation of water-soluble drugs in solid nanoparticles was developed. Nanoparticles were prepared from a blend of biodegradable polymers, including poly(lactic acid) (PLA) and poly(lactic/glycolic acid) (PLGA), and monomethoxypolyethyleneglycol-polylactide block copolymer by an oil-in-water solvent diffusion method. Betamethasone sodium phosphate (BP) was not encapsulated by the nanoparticles due to its hydrophilicity, but it was effectively encapsulated in the presence of appropriate amounts of zinc and diethanolamine. It was found that BP formed an ionic complex with zinc at a certain pH range obtained by addition of diethanolamine. Furthermore, a carboxyl group located at the end of PLA/PLGA was shown to be essential for encapsulation of BP in nanoparticles, and the molar ratio among BP, zinc, and carboxyl groups in various nanoparticles was almost constant. These results strongly suggested that the encapsulation was promoted by zinc creating an ionic bridge between a carboxyl group on PLA/PLGA and a phosphate group on BP. This technique for entrapment of water-soluble drugs in solid biodegradable nanoparticles may expand the use of nanoparticles for various therapeutic applications.
由可生物降解聚合物组成的固体纳米颗粒已成为各种药物的一种有前景的载体，但不幸的是，药物的包封仍然具有挑战性。在本研究中，开发了一种将水溶性药物包封在固体纳米颗粒中的技术。纳米颗粒由可生物降解聚合物的混合物制备而成，这些聚合物包括聚乳酸（PLA）、聚乳酸/乙醇酸共聚物（PLGA）以及单甲氧基聚乙二醇-聚丙交酯嵌段共聚物，采用水包油溶剂扩散法制备。由于倍他米松磷酸钠（BP）具有亲水性，纳米颗粒无法对其进行包封，但在适量锌和二乙醇胺存在的情况下，它能被有效包封。研究发现，通过添加二乙醇胺在一定pH范围内，BP与锌形成了离子复合物。此外，位于PLA/PLGA末端的羧基对于BP在纳米颗粒中的包封至关重要，并且不同纳米颗粒中BP、锌和羧基之间的摩尔比几乎恒定。这些结果有力地表明，锌通过在PLA/PLGA上的羧基和BP上的磷酸基团之间形成离子桥促进了包封。这种将水溶性药物包裹在固体可生物降解纳米颗粒中的技术可能会扩大纳米颗粒在各种治疗应用中的使用。
