Kakde Deepak, Taresco Vincenzo, Bansal Kuldeep K, Magennis E Peter, Howdle Steven M, Mantovani Giuseppe, Irvine Derek J, Alexander Cameron
School of Pharmacy, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
J Mater Chem B. 2016 Nov 28;4(44):7119-7129. doi: 10.1039/c6tb01839d. Epub 2016 Oct 20.
Here we describe a methoxy poly(ethyleneglycol)-b-poly(ε-decalactone) (mPEG-b-PεDL) copolymer and investigate the potential of the copolymer as a vehicle for solubilisation and sustained release of indomethacin (IND). The indomethacin loading and release from mPEG-b-PεDL micelles (amorphous cores) was compared against methoxy poly(ethyleneglycol)-b-poly(ε-caprolactone)(mPEG-b-PCL) micelles (semicrystalline cores). The drug-polymer compatibility was determined through a theoretical approach to predict drug incorporation into hydrated micelles. Polymer micelles were prepared by solvent evaporation and characterised for size, morphology, indomethacin loading and release. All the formulations generated spherical micelles but significantly larger mPEG-b-PεDL micelles were observed compared to mPEG-b-PCL micelles. A higher compatibility of the drug was predicted for PCL cores based on Flory-Huggins interaction parameters (χ) using the Hansen solubility parameter (HSP) approach, but higher measured drug loadings were found in micelles with PεDL cores compared to PCL cores. This we attribute to the higher amorphous content in the PεDL-rich regions which generated higher micellar core volumes. Drug release studies showed that the semicrystalline PCL core was able to release IND over a longer period (80% drug release in 110 h) compared to PεDL core micelles (80% drug release in 72 h).
在此,我们描述了一种甲氧基聚(乙二醇)-b-聚(ε-癸内酯)(mPEG-b-PεDL)共聚物,并研究了该共聚物作为吲哚美辛(IND)增溶和缓释载体的潜力。将吲哚美辛在mPEG-b-PεDL胶束(无定形核)中的负载和释放情况与甲氧基聚(乙二醇)-b-聚(ε-己内酯)(mPEG-b-PCL)胶束(半结晶核)进行了比较。通过理论方法预测药物掺入水合胶束中来确定药物-聚合物的相容性。通过溶剂蒸发制备聚合物胶束,并对其尺寸、形态、吲哚美辛负载和释放进行了表征。所有制剂均产生球形胶束,但与mPEG-b-PCL胶束相比,观察到mPEG-b-PεDL胶束明显更大。基于Flory-Huggins相互作用参数(χ),使用汉森溶解度参数(HSP)方法预测PCL核与药物的相容性更高,但与PCL核胶束相比,在PεDL核胶束中测得的药物负载量更高。我们将此归因于富含PεDL区域中较高的无定形含量,其产生了更大的胶束核体积。药物释放研究表明,与PεDL核胶束(72小时内80%药物释放)相比,半结晶PCL核能够在更长时间内释放IND(110小时内80%药物释放)。