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Local penetration of doxorubicin via intrahepatic implantation of PLGA based doxorubicin-loaded implants.
Drug Delivery ( IF 6.5 ) Pub Date : 2019-12-01 , DOI: 10.1080/10717544.2019.1676842
Li Gao 1 , Qingshan Li 1 , Jie Zhang 1 , Yixin Huang 1 , Lin Deng 1 , Chenyang Li 1 , Guangping Tai 2 , Banfeng Ruan 2
Affiliation  

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.

中文翻译:

通过基于PLGA的阿霉素负载植入物的肝内植入,阿霉素的局部渗透。

阿霉素(DOX)被广泛用于各种癌症的化学疗法中。然而,静脉内施用DOX对大多数主要器官产生毒性,这限制了其临床应用。装有DOX的药物递送系统可以提供药物的持续持续释放,并在目标部位实现高药物浓度,同时降低全身毒性。另外,用DOX进行局部化疗可能是降低癌症手术后复发的有前途的方法。在这项研究中,通过熔融成型法制备了持续释放的DOX负载植入物。根据药物含量均匀性,微观形态和药物释放曲线对植入物进行了表征。此外,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了肝内植入DOX的植入物。用UPLC-MS / MS法检测肝组织中DOX的浓度。我们的结果表明,装有DOX的植入物可以在植入部位长期输送高剂量的药物,并为未来装有DOX的植入物的临床应用提供有价值的信息。用UPLC-MS / MS法检测肝组织中DOX的浓度。我们的结果表明,装有DOX的植入物可以在植入部位长期输送高剂量的药物,并为未来装有DOX的植入物的临床应用提供有价值的信息。用UPLC-MS / MS法检测肝组织中DOX的浓度。我们的结果表明,装有DOX的植入物可以在植入部位长期输送高剂量的药物,并为未来装有DOX的植入物的临床应用提供有价值的信息。
更新日期:2019-11-06
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