Therapeutic Efficacy of Cisplatin Thermosensitive Liposomes upon Mild Hyperthermia in C26 Tumor Bearing BALB/c Mice

Abstract

This study reports on the activity of thermosensitive liposomes (TSLs) incorporating different HSPC ratios in DPPC/MSPC/PEG-DSPE matrix (90/10/4) plus mild hyperthermia (HT) (42 °C). TSLs were loaded with a poorly membrane permeable anticancer drug, cisplatin, through the passive equilibration method. The addition of HSPC to the corresponding DPPC lipid matrix increased the transition temperature. In vitro data demonstrated >90% cisplatin leakage from nanosized DPPC 90-lyso-TSL (LTSL) within 10 min at 42 °C, while other TSLs bearing HSPC showed greater stability. The plasma kinetics of cisplatin demonstrated higher cisplatin leakage from DPPC 90-LTSL in the first 4 h (from 17.4 to 0.4 μg/mL) compared to other formulations. Indeed, increasing HSPC fraction in liposome bilayers significantly improved drug retention in blood. Though DPPC 90-LTSL plus one-step HT was expected to provide a unique drug release, the premature drug leakage as well as the likely wash-back of a great portion of drug into the blood circulation resulted in reduced survival. On the other hand, stabilized DPPC 30/HSPC 60/MSPC 10/PEG-DSPE 4 liposomes plus two-step HT greatly enhanced the survival of animals. In particular, the improved delivery of cisplatin through stabilized DPPC 30/HSPC 60/MSPC 10/PEG-DSPE 4 liposomes in two-step mild HT enhanced antitumor efficacy compared to other formulations. Thus, prolonged exposure of cancer cells to cisplatin through stabilized liposomes would be an efficient approach in improving the survival of animals.

Analysis of the Metabolic Characteristics of Serum Samples in Patients With Multiple Myeloma

“…A series of studies have reported that the combination of PC(16:0/16:0) and an anti-cancer agent results in fast treatment efficacy in treatment of lung cancer, breast cancer and colon cancer (Alavizadeh et al, 2017 ; Tagami et al, 2017 ; Tran et al, 2017 ). Also, the abundance of phosphatidylcholines is commonly altered in various tumors.…”

Enhanced Efficacy of PEGylated Liposomal Cisplatin: In Vitro and In Vivo Evaluation

“…The results showed that the nanoparticles caused a significant reduction in the tumor volume compared to when Cispt was used (tumor volumes of 0.68 and 0.3 cm 3 in Cispt and Cispt-loaded NDAT nanoparticles receiver animals, respectively). Liposome nanoparticles are another delivery system, which are widely used for the treatment of cancer in in vitro and in vivo environments [9,12,13].…”

Whole-body hyperthermia combined with chemotherapy and intensity-modulated radiotherapy for treatment of advanced nasopharyngeal carcinoma: a retrospective study with propensity score matching

“…Heating can render head and neck squamous carcinoma cells hypersensitive to chemotherapy [17] and several studies in culture [18][19][20][21][22][23] and mice [24] have shown that heating increases the level of cytotoxicity of cisplatin to 1.59-4.96 [25]. A clinical study showed good response among patients with high-grade neuroendocrine and pancreatic cancers receiving WBH in combination with cisplatin, gemcitabine and interferon-alpha [26].…”