School of Food and Biological Engineering, Hefei University of Technology, Hefei, People's Republic of China.
Key Lab of Biofabrication of Anhui Higher Education Institution Centre for Advanced Biofabrication, Hefei University, Hefei, People's Republic of China.
Drug Deliv. 2019 Dec;26(1):1049-1057. doi: 10.1080/10717544.2019.1676842.
Doxorubicin (DOX) is widely used in the chemotherapy of a wide range of cancers. However, intravenous administration of DOX causes toxicity to most major organs which limits its clinical application. DOX-loaded drug delivery system could provide a continuous sustained-release of drugs and enables high drug concentrations at the target site, while reducing systemic toxicity. Additionally, local chemotherapy with DOX may be a promising approach for lowering post-surgical recurrence of cancer. In this study, the sustained-release DOX-loaded implants were prepared by melt-molding method. The implants were characterized with regards to drug content uniformity, micromorphology and drug release profiles. Furthermore, differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) analyses were carried out to investigate the drug-excipient compatibility. To determine the local penetration of DOX in liver, the minipigs received intrahepatic implantation of DOX-loaded implants by abdominal surgery. UPLC-MS/MS method was used to detect the concentration of DOX in liver tissues. Our results suggested that DOX-loaded implants delivered high doses of drug at the implantation site for a prolonged period and provided valuable information for the future clinical applications of the DOX-loaded implants.
多柔比星（DOX）广泛用于多种癌症的化疗。然而，DOX 静脉给药会导致大多数主要器官的毒性，从而限制了其临床应用。DOX 载药系统可以提供药物的持续缓释，并使靶部位的药物浓度升高，同时降低全身毒性。此外，DOX 局部化疗可能是降低癌症术后复发的一种有前途的方法。在这项研究中，通过熔融成型法制备了多柔比星载药的缓释植入物。对植入物的药物含量均匀性、微观形态和药物释放曲线进行了表征。此外，还进行了差示扫描量热法（DSC）和傅里叶变换红外光谱（FTIR）分析，以研究药物-赋形剂的相容性。为了确定 DOX 在肝脏中的局部渗透，小型猪通过腹部手术接受肝内植入 DOX 载药植入物。采用 UPLC-MS/MS 法检测肝组织中 DOX 的浓度。我们的结果表明，DOX 载药植入物在植入部位长时间内提供了高剂量的药物，并为 DOX 载药植入物的未来临床应用提供了有价值的信息。
