Abeylath Sampath C, Turos Edward, Dickey Sonja, Lim Daniel V
Center for Molecular Diversity in Drug Design, Discovery, and Delivery, Department of Chemistry, CHE 205, 4202 East Fowler Avenue, University of South Florida, Tampa, FL 33620, USA.
Bioorg Med Chem. 2008 Mar 1;16(5):2412-8. doi: 10.1016/j.bmc.2007.11.052. Epub 2007 Nov 28.
This report describes the synthesis and evaluation of glycosylated polyacrylate nanoparticles that have covalently-bound antibiotics within their framework. The requisite glycosylated drug monomers were prepared from one of three known antibiotics, an N-sec-butylthio beta-lactam, ciprofloxacin, and a penicillin, by acylation with 3-O-acryloyl-1,2-O-isopropylidene-5,6 bis((chlorosuccinyl)oxy)-d-glucofuranose (7) or 6-O-acetyl-3-O-acryloyl-1,2-O-isopropylidene-5-(chlorosuccinyl)oxy-alpha-d-glucofuranose (10). These acrylated monomers were subjected to emulsion polymerization in a 7:3 (w:w) mixture of butyl acrylate-styrene in the presence of sodium dodecyl sulfate as surfactant (3 weight %) and potassium persulfate as a radical initiator (1 weight %). The resulting nanoparticle emulsions were characterized by dynamic light scattering and found to have similar diameters ( approximately 40 nm) and size distributions to those of our previously studied systems. Microbiological testing showed that the N-sec-butylthio beta-lactam and ciprofloxacin nanoparticles both have powerful in vitro activities against methicillin-resistant Staphylococcus aureus and Bacillus anthracis, while the penicillin-bound nanoparticles have no antimicrobial activity. This indicates the need for matching a suitable antibiotic with the nanoparticle carrier. Overall, the study shows that even relatively large, polar acrylate monomers (MW>1000 amu) can be efficiently incorporated into the nanoparticle matrix by emulsion polymerization, providing opportunities for further advances in nanomedicine.
本报告描述了框架内共价结合抗生素的糖基化聚丙烯酸酯纳米颗粒的合成与评价。所需的糖基化药物单体由三种已知抗生素之一（N-仲丁硫基β-内酰胺、环丙沙星和青霉素）通过与3-O-丙烯酰基-1,2-O-异亚丙基-5,6-双（（氯琥珀酰）氧基）-D-葡萄糖呋喃糖（7）或6-O-乙酰基-3-O-丙烯酰基-1,2-O-异亚丙基-5-（氯琥珀酰）氧基-α-D-葡萄糖呋喃糖（10）酰化制备。这些丙烯酸化单体在十二烷基硫酸钠作为表面活性剂（3重量%）和过硫酸钾作为自由基引发剂（1重量%）存在下，于丙烯酸丁酯-苯乙烯7:3（w:w）混合物中进行乳液聚合。通过动态光散射对所得纳米颗粒乳液进行表征，发现其直径（约40 nm）和尺寸分布与我们先前研究的体系相似。微生物学测试表明，N-仲丁硫基β-内酰胺和环丙沙星纳米颗粒对耐甲氧西林金黄色葡萄球菌和炭疽芽孢杆菌均具有强大的体外活性，而结合青霉素的纳米颗粒则无抗菌活性。这表明需要将合适的抗生素与纳米颗粒载体相匹配。总体而言，该研究表明，即使是相对较大的极性丙烯酸酯单体（MW>1000 amu）也可通过乳液聚合有效掺入纳米颗粒基质中，为纳米医学的进一步发展提供了机会。
