Spatial distribution of intraperitoneally administrated paclitaxel nanoparticles solubilized with poly (2‐methacryloxyethyl phosphorylcholine‐co n‐butyl methacrylate) in peritoneal metastatic nodules

Abstract

Intraperitoneal (i.p.) administration of paclitaxel nanoparticles (PTX‐30W) prepared by solubulization with the amphiphilic copolymer of 2‐methacryloxyethyl phosphorylcholine and n‐butyl methacrylate can efficiently suppress the growth of peritoneal metastasis. In this study, we characterized the drug distribution of i.p. injected PTX‐30W in peritoneal tumor and liver in a mouse model using MKN45, human gastric cancer cells. Oregon green‐conjugated PTX‐30W showed perivascular accumulation in MKN45 tumor in the peritoneum at 24 h after intravenous (i.v.) injection; however, the amount of PTX in tumor was markedly less than that in liver. In contrast, a larger amount of PTX accumulated in the peripheral area of disseminated nodules at 1 h after i.p. injection and the area gradually enlarged. The depth of PTX infiltration reached 1 mm from the tumor surface at 48 h after i.p. injection, and the fluorescence intensity was markedly greater than that in liver. Interestingly, i.p. injected PTX preferentially accumulated in relatively hypovascular areas, and many tumor cells in the vicinity of PTX accumulation showed apoptosis. This unique accumulation pattern and lesser washout in hypovascular areas are thought to be attributable to the superior penetrating activity of PTX‐30W, and thus, PTX‐30W is considered to be highly suitable for i.p. chemotherapy for peritoneal dissemination. (Cancer Sci 2011; 102: 200–205)

A phase 2 trial of intravenous and intraperitoneal paclitaxel combined with S‐1 for treatment of gastric cancer with macroscopic peritoneal metastasis

“…The IP‐administered anticancer drug directly exposes the disseminated cancer nodules in the peritoneal cavity to drug infiltration . We demonstrated in a mouse model that IP‐administered PTX infiltrates approximately at least 100 to 200 μm from the surface of the disseminated tumor within 24 hours . In contrast, even if anticancer drugs are IV administered, most of them cannot cross the peritoneum–serum barrier and, therefore, cannot adequately reach the disseminated nodule …”

Paclitaxel-Loaded Polymersomes for Enhanced Intraperitoneal Chemotherapy

“…ABX is used for treating patients with breast, lung, and pancreatic cancers, and is undergoing clinical evaluation for IP treatment of advanced cancer in the peritoneal cavity. Compared to free anticancer drugs, IP administered nano-formulated drugs have superior antitumor activity in PC (7–11). Nanoparticles can be loaded with poorly soluble hydrophobic anticancer drugs, allowing for higher tumor drug exposure for sustained antitumor activity and enhanced tumor penetration.…”

Engineering Multifunctional Gold Decorated Dendritic Mesoporous Silica/Tantalum Oxide Nanoparticles for Intraperitoneal Tumor‐Specific Delivery

“…Our long‐term goal is to enhance radiation therapy efficacy by using imaging agents and radiosensitizers to deliver and concentrate the radiation in the tumor areas. Recent studies showed improved therapeutic outcomes when NPs are injected directly via the IP route compared to IV injection . With this method, NPs are retained in the peritoneal cavity and, thus, have more opportunity to target tumor masses.…”