Fülöp Zoltán, Saokham Phennapha, Loftsson Thorsteinn
Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, Reykjavík 107, Iceland.
Int J Pharm. 2014 Sep 10;472(1-2):282-7. doi: 10.1016/j.ijpharm.2014.06.039. Epub 2014 Jun 24.
Metastable polymer/cyclodextrin nano- and microparticles (NPs) were prepared from low molecular weight chitosan (CS), Mw about 10 kDa, and sulfobutylether β-cyclodextrin (SBEβCD). CS is a cationic polysaccharide containing numerous protonated amino groups (pKa about 6.5). SBEβCD is a β-cyclodextrin derivative with six to seven negatively charged sulfobutyl ether groups per cyclodextrin molecule. Ionotropic gelation technique was used to prepare the NPs. The NP matrix was composed of low molecular weight cationic CS polysaccharide cross-linked with polyvalent anions (SBEβCD). The diameter of the NPs ranged from 200 to almost 1,000 nm and was controlled by the CS:SBEβCD molar ratio during NP preparation. Hydrocortisone (HC) is a lipophilic drug with limited aqueous solubility (0.3mg/ml). HC displayed AL-type phase-solubility diagrams in aqueous solutions containing either SBEβCD or CS, although CS had negligible solubilizing effect. The ability of the NPs to encapsulate HC decreased with increasing CS concentration during preparation of the NPs even though the SBEβCD content of the NPs increased with increasing CS concentration. This decrease in HC encapsulation was related to the concentration; the ionic crosslinking provides better encapsulation at low initial SBEβCD and CS concentrations.
采用低分子量壳聚糖（CS，分子量约10 kDa）和磺丁基醚β-环糊精（SBEβCD）制备了亚稳聚合物/环糊精纳米和微粒（NP）。CS是一种含有大量质子化氨基（pKa约为6.5）的阳离子多糖。SBEβCD是一种β-环糊精衍生物，每个环糊精分子含有六到七个带负电荷的磺丁基醚基团。采用离子凝胶技术制备NP。NP基质由与多价阴离子（SBEβCD）交联的低分子量阳离子CS多糖组成。NP的直径范围为200至近1000 nm，并在NP制备过程中由CS:SBEβCD摩尔比控制。氢化可的松（HC）是一种亲脂性药物，水溶性有限（0.3mg/ml）。尽管CS的增溶作用可忽略不计，但HC在含有SBEβCD或CS的水溶液中显示出AL型相溶解度图。在NP制备过程中，随着CS浓度的增加，NP包封HC的能力下降，尽管NP中SBEβCD的含量随着CS浓度的增加而增加。HC包封率的这种下降与浓度有关；离子交联在低初始SBEβCD和CS浓度下提供了更好的包封效果。
