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| 1 | Tumor cell targeting of liposome -entrapped drugs with phospholipid -anchored folic acid -PEG conjugates显示文摘 | Alberto Gabizon Hilary Shmeeda Aviva T | 2004 | Adva Drug Delivery Rev2004，56，8： | 1 |
| 2 | Liposome co-encapsulation of anti-cancer agents for pharmacological optimization of nanomedicine-based combination chemotherapy显示文摘Aim:Co-encapsulation of anti-cancer agents in pegylated liposomes may provide an effective tool to maximize efficacy of combined drug therapy by taking advantage of the long circulation time,passive targeting,and reduced toxicity of liposome formulations.Methods:We have developed several liposome formulations of co-encapsulated drugs using various permutations of three active agents:doxorubicin(Dox),mitomycin-C lipidic prodrug(MLP),and alendronate(Ald).Dox and MLP are available in single drug liposomal formulations:pegylated liposomal Dox(PLD,Doxil®),clinically approved,and pegylated liposomal MLP(PL-MLP,Promitil®),in phase 1-2 clinical testing.We have previously shown that co-encapsulation of Dox and Ald in pegylated liposomes(PLAD)results in a formulation with valuable immuno-pharmacologic properties and superior antitumor properties over PLD in immunocompetent animal models.Building on the PLAD and PL-MLP platforms,we developed a new pegylated liposomal formulation of co-entrapped Dox and MLP(PLAD-MLP),with the former localized in the liposome water phase via remote loading with an ammonium alendronate and the latter passively loaded into the liposome lipid bilayer.An alternative formulation of co-entrapped MLP and Dox in which ammonium Ald was replaced with ammonium sulfate(PLD-MLP)was also tested for comparative purposes.Results: PLAD-MLP displays high loading efficiency of Dox and MLP nearing 100%, and a mean vesicle diameter of 110 nm. Cryo-transmission electron microscopy (cryo-TEM) of PLAD-MLP reveals round vesicles with an intra-vesicle Dox-alendronate precipitate. PLAD-MLP was tested in an in vitro MLP activation assay with the reducing agent dithiothreitol and found to be significantly less susceptible to thiolytic activation than PL-MLP. Alongside thiolytic activation of MLP, a significant fraction of encapsulated Dox was released from liposomes. PLAD-MLP is stable upon in vitro incubation in human plasma with nearly 100% drug retention. In mouse pharmacokinetic studies, PLAD-MLP extended MLP half-life in circulation when compared to that of MLP delivered as PL-MLP. In addition, the MLP levels in tissues were greater than those obtained with PL-MLP, indicating that PLAD-MLP slows down the cleavage of the prodrug MLP to MMC, thus resulting in a more sustained and prolonged exposure. The circulation half-life of Dox in PLAD-MLP was similar to the PLD Dox half-life. The pattern of tissue distribution was similar for the co-encapsulated drugs, although Dox levels were generally higher than those of MLP, as expected from cleavage of MLP to its active metabolite MMC. In mouse tumor models, the therapeutic activity of PLAD-MLP was superior to PL-MLP and PLD with a convenient safety dose window. The Ald-free formulation, PLD-MLP, displayed similar pharmacokinetic properties to PLAD-MLP, but its therapeutic activity was lower. Conclusion: PLAD-MLP is a novel multi-drug liposome formulation with attractive pharmacological properties and powerful antitumor activity and is a promising therapeutic tool for combination cancer chemotherapy. | Alberto Gabizon Patricia Ohana Yasmine Amitay Jenny Gorin Dina Tzemach Lidia Mak Hilary Shmeeda | 2021 | Cancer Drug Resistance2021，4，2： | 1 |
| 3 | Activation of complement by therapeutic liposomes and other lipid ex-cipient-based therapeutic products:Prediction and prevention显示文摘 | JANOS SZEBENI FRANCO MUGGIA ALBERTO GABIZON | 2011 | Ad-vanced Drug Delivery Reviews2011，63，1216： | 1 |
| 4 | Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid–PEG conjugates显示文摘 | Alberto Gabizon Hilary Shmeeda Aviva T. Horowitz Samuel Zalipsky | 2004 | Advanced Drug Delivery Reviews2004，，8： | 1 |
| 5 | Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid-PEG conjugates显示文摘 | Alberto Gabizon Hilary Shmeeda Aviva T | 2004 | Adva Drug Delivery Rev2004，56，8： | 1 |
| 6 | Pegylated liposomal doxorubicin/carboplatin combination in ovarian cancer, progressing on single-agent pegylated liposomal doxorubicin显示文摘AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin(PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma(ROC), following disease progression on single agent PLD. METHODS: An analysis of the medical records of 10 patients with ROC, treated in our institution with a combination of PLD and carboplatin following progression on single-agent PLD therapy was performed. The median age was 59.1 years(range, 45 to 77 years). All diagnoses were histological-proven. Eight of the 10 patients were platinum-resistant. Following disease progression on single-agent PLD treatment, carboplatin area under the curve(AUC)-5 was added to PLD in all 10 patients. In order to assess disease status, Ca-125 was assessed before each PLD/carboplatin treatment. Relative changes in Ca-125 values were calculated, and response defined as a greater than 50% reduction in Ca-125 from baseline. Radiographic studies were reevaluated and responses to therapy based on com-puter tomography(CT) scans carried out on a regular basis every 2-3 mo in each patient. Statistical analysis was performed using SPSS(V19).RESULTS: A median of 10 cycles(range, 2-26) of the carboplatin-PLD combination was given. Of the 10 treated patients, 6 had > 50% reduction in Ca-125 levels from baseline, 4 of these had a partial response according to Response Evaluation Criteria in Solid Tumors(RECIST) criteria, and the other 2 patients had no measurable disease. In a further 2 patients with a best response of disease stabilization and < 50% reduction of Ca-125 levels, one had progression of disease after 26 cycles, and the second progressed with brain metastases following 12 cycles. Seven of the eight patients who were platinum-resistant showed evidence of clinical benefit on carboplatin-PLD combination therapy; 5 of these had > 50% reduction in Ca-125 level, 4 also showed a partial response on CT scan. The treatment was generally well-tolerated by the patients. CONCLUSION: Addition of carboplatin to PLD, after disease progression on single-agent PLD therapy, is both effective and safe in patients with ROC, even in those with Platinum-resistant disease. | Tal Grenader Ora Rosengarten Rut Isacson Yevgeni Plotkin Alberto Gabizon | 2012 | World Journal of Clinical Oncology2012，3，10： | 0 |
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