Biodistribution of etoposide via intratumoral chemotherapy with etoposide-loaded implants

Abstract

Etoposide (VP16) is the traditional antitumor agent which has been widely used in a variety of cancers. However, intravenous administration of VP16 was limited in clinical application because of its low aqueous solubility, poor bioavailability and dose-limiting adverse effects. Local chemotherapy with VP16-loaded drug delivery systems could provide a continuous release of drug at the target site, while minimizing the systemic toxicity. In this study, we prepared the poly- l -lactic acid (PLLA) based VP16-loaded implants (VP16 implants) by the direct compression method. The VP16 implants were characterized with regards to drug content, micromorphology, drug release profiles, differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) analyses. Furthermore, the biodistribution of VP16 via intratumoral chemotherapy with VP16 implants was investigated using the murine Lewis lung carcinoma model. Our results showed that VP16 dispersed homogenously in the polymeric matrix. Both in vitro and in vivo drug release profiles of the implants were characterized by high initial burst release followed by sustained release of VP16. The VP16 implants showed good compatibility between VP16 and the excipients. Intratumoral chemotherapy with VP16 implants resulted in significantly higher concentration and longer duration of VP16 in tumor tissues compared with single intraperitoneal injection of VP16 solution. Moreover, we found the low level of VP16 in plasma and normal organ tissues. These results suggested that intratumoral chemotherapy with VP16 implants enabled high drug concentration at the target site and has the potential to be used as a novel method to treat cancer.

An Implantable Magnetic Vascular Scaffold for Circulating Tumor Cell Removal In Vivo

“…The bionic vascular scaffold prolonged the capture time by at least six months, mainly dependent on the degradable material type (PLLA for this work). [ 25 ] The capture efficiency of HA‐MVS increased in a time‐dependent manner, with 92% of the captured cells eliminated in vitro and in vivo.…”

Implantation of In Situ Gelling Systems for the Delivery of Chemotherapeutic Agents

“…As previously discussed, chemotherapy is a widely used approach for cancer treatment, although it has drawbacks. High doses of chemotherapy can cause systemic toxicity, and the presence of large tumors can lead to poor pharmacokinetics due to interstitial fluid pressure, hindering transcapillary transport and preventing substance penetration into the tumor [31].…”

Etoposide‐Entrapped Progesterone‐Cationic Lipid Nanoaggregates as Selective Therapeutics against Etoposide‐Resistant Colorectal Cancer Cells

“…Kasahara et al reported in 1992 that within lung cancers, small cell lung carcinomas (SCLCs) were more sensitive to etoposide than non-small-cell lung carcinomas (NSCLCs). [12] Following this, Dong et al showed that in NSCLC cell lines, etoposide causes a sequential increase in ROS production, glycolysis and lactate production. This ultimately leads to increased expression of MRP1/ABCC1 protein that is responsible for conferring drug resistance by causing efflux.…”

“…Kasahara et al. reported in 1992 that within lung cancers, small cell lung carcinomas (SCLCs) were more sensitive to etoposide than non‐small‐cell lung carcinomas (NSCLCs) [12] . Following this, Dong et al.…”