Abstract
Colorectal cancer with peritoneal metastasis has a poor prognosis because of inadequate responses to systemic chemotherapy. Cytoreductive surgery followed by intraperitoneal (IP) chemotherapy using oxaliplatin has attracted attention; however, the short half-life of oxaliplatin and its rapid clearance from the peritoneal cavity limit its clinical application. Here, a multivesicular liposomal (MVL) depot of oxaliplatin was prepared for IP administration, with an expected prolonged effect. After optimization, a combination of phospholipids, cholesterol, and triolein was used based on its ability to produce MVL depots of monomodal size distribution (1–20 µm; span 1.99) with high entrapment efficiency (EE) (92.16% ± 2.17%). An initial burst release followed by a long lag phase of drug release was observed for the MVL depots system in vitro. An in vivo pharmacokinetic study mimicking the early postoperative IP chemotherapy regimen in rats showed significantly improved bioavailability, and the mean residence time of oxaliplatin after IP administration revealed that slow and continuous erosion of the MVL particles yielded a sustained drug release. Thus, oxaliplatin-loaded MVL depots presented in this study have potential for use in the treatment of colorectal cancer.
Highlights
Cancers that spread within the peritoneal cavity were deemed fatal [1,2,3]
Colorectal cancer (CRC) with peritoneal metastasis shows poor survival and prognosis compared with other metastatic sites [4,5]
We developed liposomal depots containing oxaliplatin by the double-emulsion method
Summary
Cancers that spread within the peritoneal cavity were deemed fatal [1,2,3]. CRC with peritoneal metastasis shows poor survival and prognosis compared with other metastatic sites [4,5]. Systemic chemotherapy has very little effect on improving survival once malignancies have proliferated to the peritoneum; the inadequate blood supply to the peritoneal surface results in low drug stream into tumors [7]. Weissberger (1955) originally introduced the idea of intraperitoneal (IP) chemotherapy for the treatment of peritoneal cancers; later, Dedrick peritoneal surface results in low drug stream into tumors [7]. Weissberger (1955) originally Pihnartmroacdeuutcicesd20t2h0e, 1i2d,e7a36of intraperitoneal (IP) chemotherapy for the treatment of peritoneal cancers;2loaft1e7r, Dedrick (1978) observed 1–3-mm tissue penetration by several cytotoxic drugs after IP chemotherapy (1[89]7.8T) hoebsuenrvdeedrly1i–n3g-mpmrintciispsluee fpoerntehteraatidomn ibnyistsreavtieornal ocfytIoPtocxhiecmdoruthgesraapftyerisIPtocheenmaboltehethraepdyir[8e]c.t Tehxepuonsudreerloyfincygtpotroinxcicipdlerufogrs,tahleoandgmwiinthistrhaetitounmoofrIcPecllhse, wmiotthhoeurat phyavisintgo teonraebllyeothnethdeirseycsttexmpiocssuurpepolfy ctyotothtoexaicredar.ugs, along with the tumor cells, without having to rely on the systemic supply to the area
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