Sustained Release of Cisplatin from Drug Delivery System Based on PCL Membrane

To develop a sustained drug delivery system based on PCL membrane, promoting pleural adhesion, for the treatment of malignant pleural effusion (MPE), cisplatin (CDDP)-encapsulated PLGA nanoparticles (PLGA/CDDP NPs) were fabricated via solvent displacement method for the purpose of prolonging drug delivery. The PCL membrane incorporating CDDP and PLGA/CDDP NPs (PLGA/CDDP NP-PCL/CDDP membrane) was investigated under the in vitro and in vivo conditions with the comparison of PCL membrane incorporating CDDP (PCL/CDDP membrane) and free CDDP in solution form. As nanoscale drug carriers, the PLGA/CDDP NPs released the drug in a long-term manner for a longer period than PCL/CDDP membrane and were also less cytotoxic than free CDDP and PCL/CDDP membrane which probably due to the slower release of CDDP from NPs. The tumor-suppressing ability was observed that PLGA/CDDP NP-PCL/CDDP membrane could successfully inhibit the tumor growth after 17days because of the sustained release of CDDP in tumor-bearing mice, as shown by changes in tumor volumes, body weights, and survival trends. Histological analysis of tumor sections on Day 21 also showed that PLGA/CDDP NP-PCL/CDDP membrane had an obvious anti-tumor effect than other treatments. In addition, there was no significant difference of abdominal adhesion effect between the PLGA NP-PCL membrane and the porous PCL membrane probably because PCL membrane blended with PLGA NPs also had the porous surface structure facilitating the adhesion response without influencing the living conditions of rats. As expected, PLGA NP-PCL membrane system can also be used as two-step drug delivery system serving as a promising new treatment for MPE.