Comparing the cytotoxicity of taurolidine, mitomycin C, and oxaliplatin on the proliferation of in vitro colon carcinoma cells following pressurized intra-peritoneal aerosol chemotherapy (PIPAC)

Abstract

Background Besides its known antibacterial effect commonly used in intraperitoneal lavage, taurolidine has been observed to possess antineoplastic properties. In order to analyse this antineoplastic potential in a palliative therapeutic setting, taurolidine (TN) was compared to mitomycin C (MMC) and oxaliplatin (OX), known antineoplastic agents which are routinely used in intraperitoneal applications, following pressurized intra-peritoneal aerosol chemotherapy (PIPAC). Methods An in vitro model was established using a colon adenocarcinoma cell line (HT-29 human cells). Different experimental dosages of TN and combinations of TN, MMC, and OX were applied via PIPAC. To measure cell proliferation, a colorimetric tetrazolium reduction assay was utilized 24 h after PIPAC. Results We demonstrated a cytotoxic effect of TN and OX (184 mg/150 mL, p < 0.01) on tumor cell growth. An increasing dosage of TN (from 0.5 g/100 mL to 0.75 g/150 mL) correlated with higher cell toxicity when compared to untreated cells ( p < 0.05 and p < 0.01, respectively). PIPAC with OX and both OX and TN (0.5 g/100 mL) showed the same cytotoxic effect ( p < 0.01). No significant impact was observed for MMC (14 mg/50 mL, p > 0.05) or MMC with OX ( p > 0.05) applied via PIPAC. Conclusions The intraperitoneal application of TN is mostly limited to lavage procedures in cases of peritonitis. Our results indicate a substantial antineoplastic in vitro effect on colon carcinoma cells following PIPAC application. While this effect could be used in the palliative treatment of peritoneal metastases, further clinical studies are required to investigate the feasibility of TN application in such cases.

Overcoming Drug Resistance by Taking Advantage of Physical Principles: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)

“…A maximum cytotoxicity was observed at 15 mmHg. Pressures >15 mmHg did not show additional cytotoxic effect on cells [88]. Similarly, increasing PIPAC pressure over 15 mmHg did not increase the depth of doxorubicin tissue penetration in an ex vivo model [84].…”

“…Several studies have evaluated drug uptake into the target tissue after PIPAC, and some of them have compared PIPAC with other drug delivery techniques such as HIPEC and/or laparoscopic HIPEC. Therapeutic substances investigated include methylene blue [28,76], DNA [77], RNA [29,78], cisplatin [79][80][81][82], doxorubicin [75,[83][84][85], oxaliplatin [82,[86][87][88] and liposomal doxorubicin [89,90].…”

“…Thus, homogeneity of drug distribution after PIPAC is not ideal. Several studies ex vivo and in animal models have shown an increasing drug gradient from the top to the bottom of the target volume, as well as a decreasing gradient from the axis of the aerosolizing device towards the periphery [84][85][86]88,101]. The addition of electrostatic precipitation (so-called ePIPAC) reduced the influence of gravity and improved homogeneity of drug repartition.…”

Creating nanocrystallized chemotherapy: the differences in pressurized aerosol chemotherapy (PAC) via intracavitary (IAG) and extracavitary aerosol generation (EAG) regarding particle generation, morphology and structure

“…Current research on chemoaerosol applications has advanced many new concepts investigating the potential of aerosol and drug nanoparticles and their unique characteristics. While PIPAC displays limitations [12,13], its efficacy and potential benefits have also been recognized [14].…”

Increased Tissue Penetration of Doxorubicin in Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) after High-Intensity Ultrasound (HIUS)

“…e application of pressure has been proposed and was ultimately applied through pressurized intraperitoneal aerosol chemotherapy (PIPAC) in the treatment of more advanced peritoneal metastasis [6,7]. Clinical as well as experimental studies have also tested irradiation [8][9][10] and new drug formulas [11][12][13] as alternate methods of increasing chemotherapy penetration. Despite several attempts to improve penetration rates, these studies have had only limited success.…”