Pharmacokinetics and adverse reactions of a new liposomal cisplatin (Lipoplatin): Phase I study

Stathopoulos, George P.; Boulikas, Teni; Vougiouka, Maria; Deliconstantinos, George; Rigatos, Sotiris K.; Darli, Eleftheria; Viliotou, Vasiliki; Stathopoulos, J.

doi:10.3892/or.13.4.589

Cited by 66 publications

(85 citation statements)

References 22 publications

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“…Cells were allowed to proliferate upon a confluence near 70% and incubated with one of the platinum compound (10 μM) for 4 h. It is to note that the concentrations that we used in our study are similar as the concentration found in plasma in clinical use [20]. The equimolarity of the platinum compounds free and loaded in liposomes was assessed using an Inductively Coupled Plasma Mass Spectrometer (ICP-MS) (ELAN DRC-II, PerkinElmer).…”

Section: Cellular Uptake Of Platinum Compoundsmentioning

confidence: 99%

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

et al. 2009

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Despite significant advances, the radiotherapy and chemotherapy protocols marginally improve the overall survival of patients with glioblastoma. Lipoplatin ™ , and Lipoxal ™ , the liposomal formulations of cisplatin and oxaliplatin respectively, were tested on the F98 glioma cells for their ability to improve the cell uptake and increase the synergic effect when combined with ionizing radiation. The cytotoxicity and synergic effect of platinum compounds were assessed by colony formation assay, while the cellular uptake was measured by Inductively Coupled Plasma Mass Spectrometer (ICP-MS). After 4 h exposure with platinum compounds, cells were irradiated (1.5 to 6.6 Gy) with a 60 Co source. The liposomal formulations were compared to their liposome-free analogs and to carboplatin. The concomitant treatment of F98 cells with carboplatin and radiation produced the highest radiosensitizing effect (30-fold increase). Among the platinum compounds tested, Lipoplatin ™ produced the most promising results. This liposomal formulation of cisplatin improved the cell uptake by 3-fold, and its radiosensitizing potential was enhanced by 14-fold. Although Lipoxal ™ can potentially reduce the adverse effect of oxaliplatin, a synergic effect with radiation was measured only when incubated at a concentration higher than its IC50. Conversely, concomitant treatment with cisplatin did not result in a synergic effect, as in fact a radioprotective effect was measured on the F98 cells. In conclusion, among the five platinum compounds tested, carboplatin and Lipoplatin ™ showed the best radiosensitizing effect. Lipoplatin ™ seems the most promising since it led to the best cellular incorporation and has already been reported to be less neurotoxic than other platinum compounds.

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Section: Cellular Uptake Of Platinum Compoundsmentioning

confidence: 99%

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

et al. 2009

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“…222, 223 Lipoplatin crosses cell membranes more easily than native cisplatin due to the fusogenic nature of the DPPG lipids. 222 In addition, the presence of a PEG coating prevents detection by immunogenic entities.…”

Section: -222mentioning

confidence: 99%

The status of platinum anticancer drugs in the clinic and in clinical trials

et al. 2010

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Since its approval in 1979 cisplatin has become an important component in chemotherapy regimes for\ud the treatment of ovarian, testicular, lung and bladder cancers, as well as lymphomas, myelomas and\ud melanoma. Unfortunately its continued use is greatly limited by severe dose limiting side effects and\ud intrinsic or acquired drug resistance. Over the last 30 years, 23 other platinum-based drugs have entered\ud clinical trials with only two (carboplatin and oxaliplatin) of these gaining international marketing\ud approval, and another three (nedaplatin, lobaplatin and heptaplatin) gaining approval in individual\ud nations. During this time there have been more failures than successes with the development of 14 drugs\ud being halted during clinical trials. Currently there are four drugs in the various phases of clinical trial\ud (satraplatin, picoplatin, LipoplatinTM and ProLindacTM). No new small molecule platinum drug has\ud entered clinical trials since 1999 which is representative of a shift in focus away from drug design and\ud towards drug delivery in the last decade. In this perspective article we update the status of platinum\ud anticancer drugs currently approved for use, those undergoing clinical trials and those discontinued\ud during clinical trials, and discuss the results in the context of where we believe the field will develop over\ud the next decade

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“…This in turn also requires a very high lipid composition. The complexation of liposomes with caprylate ligands has provided a high entrapment of cisplatin along with reducing the lipid required to entrap cisplatin to a significant level as compared to two clinically evaluated cisplatin liposomes (SIP-077 and Lipoplatin); 1 mg/7.77 mg of prepared cisplatin liposomes against 1 mg/70 mg of SPI-077 (33), and 1 mg/10.2 mg of Lipoplatin (34).…”

Section: Discussionmentioning

confidence: 99%

Caprylate-Conjugated Cisplatin for the Development of Novel Liposomal Formulation

et al. 2014

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Abstract. Cisplatin, first (platinum) compound to be evolved as an anticancer agent, has found its important place in cancer chemotherapy. However, the dose-dependent toxicities of cisplatin, namely nephrotoxicity, ototoxicity, peripheral neuropathy, and gastrointestinal toxicity hinder its widespread use. Liposomes can reduce the toxicity of cisplatin and provide a better therapeutic action, but the low lipid solubility of cisplatin hinders its high entrapment in such lipid carrier. In the present investigation, positively charged reactive aquated species of cisplatin were complexed with negatively charged caprylate ligands, resulting in enhanced interaction of cisplatin with lipid bilayer of liposomes and increase in its encapsulation in liposomal carrier. Prepared cisplatin liposomes were found to have a vesicular size of 107.9±6.2 nm and zeta potential of −3.99±3.45 mV. The optimized liposomal formulation had an encapsulation efficiency of 96.03±1.24% with unprecedented drug loading (0.21 mg cisplatin/mg of lipids). The in vitro release studies exhibited a pH-dependent release of cisplatin from liposomes with highest release (67.55 ± 3.65%) at pH 5.5 indicating that a maximum release would occur inside cancer cells at endolysosomal pH. The prepared liposomes were found to be stable in the serum and showed a low hemolytic potential. In vitro cytotoxicity of cisplatin liposomes on A549 lung cancer cell line was comparable to that of cisplatin solution. The developed formulation also had a significantly higher median lethal dose (LD 50 ) of 23.79 mg/kg than that of the cisplatin solution (12 mg/kg). A promising liposomal formulation of cisplatin has been proposed that can overcome the disadvantages associated with conventional cisplatin therapy and provide a higher safety profile.

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Pharmacokinetics and adverse reactions of a new liposomal cisplatin (Lipoplatin): Phase I study

Cited by 66 publications

References 22 publications

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation

The status of platinum anticancer drugs in the clinic and in clinical trials

Caprylate-Conjugated Cisplatin for the Development of Novel Liposomal Formulation

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