Design and testing of a new cisplatin form using a base material by combining poly-D,L-lactic acid and polyethylene glycol acid against peritoneal metastasis

Abstract

Microspheres containing cisplatin (CDDP) embedded in poly‐d,l‐lactic acid (PLA) and polyethylene glycol acid (CDDP‐PPMS) were developed to improve treatment of malignant effusions. In vitro studies demonstrated that CDDP was released continuously for more than 4 weeks from CDDP‐PPMS without initial burst. CDDP‐PPMS was compared with CDDP aqueous solution (CDDP‐SOL) by i.p. administration in rats for 1) tissue distribution, 2) toxicity and 3) therapeutic effects against Yoshida sarcoma. We found that the CDDP concentration in the omentum was maintained at a higher level than in the CDDP‐SOL group, while the particles of CDDP‐PPMS were observed in the stomata of the omentum by electron microscopy. Concentrations of CDDP in the lung, liver, kidney and blood were lower in the CDDP‐PPMS group than in the CDDP‐SOL group. All rats given CDDP‐PPMS containing ≤28 mg/kg were alive, whereas in the CDDP‐SOL group, all rats given ≥16 mg/kg died from side effects. The LD50 of CDDP‐PPMS and CDDP‐SOL were 32.8 and 14.8 mg/kg, respectively. The survival of rats with peritoneal metastasis was better in the CDDP‐PPMS group than in the CDDP‐SOL group. Int. J. Cancer 76:709–712, 1998.© 1998 Wiley‐Liss, Inc.

Cytotoxicity and mechanism of action of a new ROS-generating microsphere formulation for circumventing multidrug resistance in breast cancer cells

“…This approach has shown promising results with higher efficacy and decreased systemic toxicity compared to systemic drug administration [29][30][31][32][33][34][35]. Our laboratory has successfully developed dextran-based microspheres for the local delivery of Dox and MDR reversal agents to solid tumors resulting in significant delays in tumor growth [32,33].…”

Trends in Microencapsulation Research

“…We have developed, so far, microcapsules with functions for separation and purification [2][3][4][5][6][7], controlled release of drugs [8][9][10][11][12][13][14][15][16][17][18][19][20], and the triboelectric property required by toner microparticles [21,22]. Hollow microcapsules and microcapsules enclosing microorganisms have also been prepared [23,24].…”

Injectable nanospheres from a novel multiblock copolymer: cytocompatibility, degradation and in vitro release studies

“…PEG-coated NS and micelles are prepared from PLA-PEG diblock (Gref et al 1994, Kreuter 1996, Tokuda et al 1998, Beletsi et al 1999. Non-linear multiblock polymers composed of methoxy-PEG and hydrophobic chains have been synthesized to increase PEG density.…”