Quaglia Fabiana, Ostacolo Luisanna, Nese Giuseppe, De Rosa Giuseppe, La Rotonda Maria Immacolata, Palumbo Rosario, Maglio Giovanni
Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli Federico II, via D. Montesano 49, 80131 Napoli, Italy.
Macromol Biosci. 2005 Oct 20;5(10):945-54. doi: 10.1002/mabi.200500108.
Microspheres of amphiphilic multi-block poly(ester-ether)s (PEE)s and poly(ester-ether-amide)s (PEEA)s based on poly(epsilon-caprolactone) (PCL) were investigated as delivery systems for proteins. The interest was mainly focused on the effect of their molecular structure and composition on the overall properties of the microspheres, encapsulating bovine serum albumin (BSA) as a model protein. PEEs and PEEAs were prepared using a alpha,omega-dihydroxy-terminated PCL macromer (Mn= 2.0 kDa) as a hydrophobic component. Hydrophilic oxyethylene sequences were generated using poly(ethylene oxide)s (PEO)s of different molecular mass (Mn= 300-600 Da) in the case of PEEs, or 4,7,10-trioxa-1,13-tridecanediamine (Trioxy) and PEO150 (Mn= 150 Da) in the case of PEEAs. The copolymers showed a decrease of Tm and crystallinity values as compared with PCL. Within each class of copolymers, the bulk hydrophilicity increased with increasing the number of oxyethylene groups in the chain repeat unit. PEEAs were more hydrophilic than PEEs with a similar number of oxyethylene groups. Discrete spherical particles were prepared by both PEEs and PEEAs and their BSA encapsulation efficiency related to copolymer properties. Interestingly, the insertion of short hydrophilic segments is enough to significantly affect protein distribution inside microspheres and its release profiles, as compared to PCL microspheres. Different degradation rates and mechanisms were observed for copolymer microspheres, mainly depending on the distribution of oxyethylene units along the chain. The results highlight that a fine control over the structural parameters of amphiphilic PCL-based multi-block copolymers is a key factor for their application in the field of protein delivery.
研究了基于聚己内酯（PCL）的两亲性多嵌段聚（酯-醚）（PEE）和聚（酯-醚-酰胺）（PEEA）微球作为蛋白质递送系统的性能。研究重点主要集中在其分子结构和组成对微球整体性能的影响上，以牛血清白蛋白（BSA）作为模型蛋白进行包封。使用α,ω-二羟基封端的PCL大分子单体（Mn = 2.0 kDa）作为疏水组分来制备PEE和PEEA。对于PEE，使用不同分子量（Mn = 300 - 600 Da）的聚环氧乙烷（PEO）来生成亲水的氧化乙烯序列；对于PEEA，则使用4,7,10-三氧杂-1,13-十三烷二胺（Trioxy）和PEO150（Mn = 150 Da）。与PCL相比，共聚物的熔点（Tm）和结晶度值有所降低。在每一类共聚物中，随着链重复单元中氧化乙烯基团数量的增加，整体亲水性增强。在氧化乙烯基团数量相似的情况下，PEEA比PEE更亲水。PEE和PEEA均制备出了离散的球形颗粒，且它们对BSA的包封效率与共聚物性能相关。有趣的是，与PCL微球相比，短亲水链段的插入足以显著影响蛋白质在微球内的分布及其释放曲线。共聚物微球观察到不同的降解速率和机制，这主要取决于氧化乙烯单元沿链的分布。结果表明，对基于PCL的两亲性多嵌段共聚物的结构参数进行精细控制是其在蛋白质递送领域应用的关键因素。
