Jansook Phatsawee, Pichayakorn Wiwat, Muankaew Chutimon, Loftsson Thorsteinn
a Faculty of Pharmaceutical Sciences , Chulalongkorn University , Pathumwan, Bangkok , Thailand ;
b Faculty of Pharmaceutical Sciences , Prince of Songkla University , Songkhla , Thailand ;
Drug Dev Ind Pharm. 2016 Sep;42(9):1446-54. doi: 10.3109/03639045.2016.1141932. Epub 2016 Feb 16.
In this present study cyclodextrin (CD)-poloxamer aggregates were characterized and developed as ophthalmic drug carriers. The combined effect of γCD/2-hydroxypropyl-γCD (HPγCD) mixtures and poloxamer on solubilization and permeability of two model drugs, dexamethasone (Dex) and amphotericin B (AmB), was investigated. The CD-poloxamer interaction and complex aggregation were examined by (1)H nuclear magnetic resonance ((1)H-NMR), their solubilizing ability by high-performance liquid chromatography, and their particle size determined by dynamic light scattering and transmission electron microscopy. Formulations containing either 1.5% w/v Dex or 0.15% w/v AmB in eye drop suspensions containing various γCD/HPγCD ratios and poloxamer 407 (P407) were prepared. The solubility of the drugs, surface tension and hemolytic effect of the eye drops and drug permeation from selected formulations were determined. The (1)H-NMR study showed that P407 formed inclusion complex with CDs by inserting its poly(propylene oxide) segment into the CD cavity. P407 and γCD interacted with each other to form nanosized aggregates, and the observed concentration of dissolved γCD and P407 progressively decreased with increasing γCD and P407 concentrations. Including a high proportion of HPγCD improved the drug solubilization and reduced the hemolytic effect. The surface tension of the formulations decreased with increasing P407 concentration. Furthermore, increasing P407 content in the formulations enhanced formation of complex aggregates with consequent slower drug release. It was concluded that the drug/γCD/HPγCD complex was stabilized by P407 through formation of multi-component aggregates. Thus, CD-poloxamer aggregates are self-assembled nanocarriers from which drug delivery characteristics can be adjusted by changing the γCD/HPγCD/P407 ratios.
在本研究中，对环糊精（CD）-泊洛沙姆聚集体进行了表征，并将其开发为眼科药物载体。研究了γ环糊精/2-羟丙基-γ环糊精（HPγCD）混合物与泊洛沙姆对两种模型药物地塞米松（Dex）和两性霉素B（AmB）的增溶作用和渗透性的联合影响。通过氢核磁共振（¹H-NMR）研究CD-泊洛沙姆的相互作用和复合物聚集，通过高效液相色谱法研究其增溶能力，通过动态光散射和透射电子显微镜测定其粒径。制备了含有不同γCD/HPγCD比例和泊洛沙姆407（P407）的滴眼剂悬浮液，其中分别含有1.5%w/v Dex或0.15%w/v AmB。测定了药物的溶解度、滴眼剂的表面张力和溶血作用以及选定制剂的药物渗透性。¹H-NMR研究表明，P407通过将其聚环氧丙烷链段插入CD腔中与CD形成包合物。P407与γCD相互作用形成纳米级聚集体，随着γCD和P407浓度的增加，观察到的溶解γCD和P407的浓度逐渐降低。包含高比例的HPγCD可改善药物增溶并降低溶血作用。制剂的表面张力随P407浓度的增加而降低。此外，制剂中P407含量的增加增强了复合物聚集体的形成，从而使药物释放更慢。得出的结论是，P407通过形成多组分聚集体使药物/γCD/HPγCD复合物稳定。因此，CD-泊洛沙姆聚集体是自组装纳米载体，可通过改变γCD/HPγCD/P407比例来调节其药物递送特性。
