14 results on '"Lee, Robert J."'
Search Results
2. Enhanced survivin siRNA delivery using cationic liposome incorporating fatty acid-modified polyethylenimine
- Author
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Yang, Shuang, Guo, Zhihua, Yang, Xuewei, Xie, Jing, Lee, Robert J., Jiang, Dan, and Teng, Lesheng
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- 2015
- Full Text
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3. Folate receptor-targeted lipid-albumin nanoparticles (F-LAN) for therapeutic delivery of an Akt1 antisense oligonucleotide.
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Li, Hong, Liu, Yang, Chen, Lihua, Liu, Qibing, Qi, Shanshan, Cheng, Xinwei, Lee, Young B., Ahn, Chang-Ho, Kim, Deog Joong, and Lee, Robert J.
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NANOPARTICLES ,ANTINEOPLASTIC agents ,XENOGRAFTS ,CANCER treatment ,CANCER cells - Abstract
Background: RX-0201 is an antisense oligonucleotide (ASO) against Akt1 currently in clinical trial for metastatic renal cancer.Purpose: To improve the delivery of RX-0201 using folate receptor-targeted lipid-albumin nanoparticles (F-LAN).Methods: F-LAN were synthesized with the composition of DOTAP/soyPC/TPGS/folate-PEG-DSPE (25:70:4:1 m/m), a cationic human serum albumin-pentaethylenehexamine (HSA-PEHA) conjugate and RX-0201. The nanoparticles were evaluated in KB human carcinoma cellsin vitro and in a KB murine xenograft tumour modelin vivo for pharmacokinetics and antitumor activities.Results: The F-LAN-RX-0201 had a mean particle size of 108.6 ± 5.8 nm, zeta potential of 10.5 ± 3.2 mV and ASO loading efficiency of 71.5 ± 4.5%. In KB cells, uptake and Akt1 inhibition by F-LAN-RX-0201 were greater than those of non-targeted LAN-RX-0201 and could be partially blocked by excess free folate. F-LAN-RX-0201 inhibited cell growth with an IC50 of 11.9 μM. In contrast, LAN-RX-0201 showed lower cytotoxicity with an IC50 of 32.0 μM. No significant cytotoxicity was observed with up to 250 µM of free RX-0201. Pharmacokinetic studies showed that F-LAN-RX-0201 had a longer terminal half-life than free RX-0201 (442 vs. 219 min). In a KB xenograft tumour model, F-LAN-RX-0201 exhibited greater tumour inhibition than LAN-RX-0201 at 16 mg/kg. Moreover, F-LAN-RX-0201 at 16 mg/kg showed comparable tumour inhibition compared to free RX-0201 at a much higher dose of 90 mg/kg.Conclusions: F-LAN-RX-0201 showed promise as a therapeutic agent for tumours with elevated folate-receptor expression. [ABSTRACT FROM AUTHOR]- Published
- 2018
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4. Enhancing anti-tumor efficiency in hepatocellular carcinoma through the autophagy inhibition by miR-375/sorafenib in lipid-coated calcium carbonate nanoparticles.
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Zhao, Pengxuan, Li, Minsi, Wang, Yao, Chen, Yan, He, Chuanchuan, Zhang, Xiaojuan, Yang, Tan, Lu, Yao, You, Jia, Lee, Robert J., and Xiang, Guangya
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ANTINEOPLASTIC agents ,LIVER cancer ,AUTOPHAGY ,MICRORNA ,SORAFENIB - Abstract
Sorafenib is a first-line drug for hepatocellular carcinoma (HCC). Autophagy has been shown to facilitate sorafenib resistance. miR-375 has been shown to be an inhibitor of autophagy. In this study, miR-375 and sorafenib were co-loaded into calcium carbonate nanoparticles with lipid coating (miR-375/Sf-LCC NPs). The nanoparticles had high loading efficiency and were ∼50 nm in diameter. Besides, the NPs could increase the stability and residence time of both drugs. Moreover, we demonstrated that autophagy was activated in HCC cells by sorafenib but not by miR-375/Sf-LCC NPs. In vitro , miR-375/Sf-LCC NPs exhibited pH-dependent drug release and potent cytotoxicity. In vivo , miR-375/Sf-LCC NPs increased miR-375 and sorafenib uptake in tumor (2 folds compared with Lipofectamine 2000-miR-375 and 2–5 folds compared with free sorafenib). Furthermore, miR-375/Sf-LCC NPs showed greatly enhanced therapeutic efficacy in an HCC xenograft model. These findings suggest that miR-375/Sf-LCC NPs may be a promising agent for the HCC therapy. Statement of Significance Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the third leading cause of cancer mortality globally. In this manuscript, miR-375 and sorafenib were co-loaded into calcium carbonate nanoparticles with lipid coating (miR-375/Sf-LCC NPs) to treat HCC. We demonstrated that miR-375/Sf-LCC NPs can deliver sorafenib and miR-375 into HCC cells and tumor tissues, increase drug retention time in tumor, significantly inhibit autophagy and produce enhanced anti-tumor effect. [ABSTRACT FROM AUTHOR]
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- 2018
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5. Determining the epidemiologic, outcome, and prognostic factors of oral malignant melanoma by using the Surveillance, Epidemiology, and End Results database.
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Lee, Robert J., Lee, Serena A., Lin, Thomas, Lee, Kevin K., and Christensen, Russell E.
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MELANOMA , *MOUTH tumors , *PROBABILITY theory , *RETROSPECTIVE studies , *DESCRIPTIVE statistics , *PROGNOSIS - Abstract
Background. The authors conducted a retrospective analysis to determine the epidemiologic, outcome, and prognostic factors in patients with oral malignant melanoma (OMM). Methods. The authors used the US National Cancer Institute's Surveillance, Epidemiology, and End Results database to analyze patients with OMM from 1973 to 2012. Study variables included age, sex, race, decade of diagnosis, extent of disease, tumor size, treatment modality, and socioeconomic status (SES). Results. The search identified 232 patients with OMM. Overall survival (OS) and disease-specific survival (DSS) were 25% and 40%, respectively, at 5 years. Age (OS, P = .004; DSS, P = .294), surgical resection (OS, P = .046; DSS, P = .005), and extent of disease (OS, P < .001; DSS, P < .001) were independent survival determinants; tumor size was an independent predictor of OS (P = .085). For confined and locally invasive disease, surgery (OS, P = .001; DSS, P = .004) and size (OS, P = .154; DSS, P = .007) were independent determinants of OS and DSS. For metastatic disease, surgery (OS, P = .675; DSS, P = .518) was a survival determinant for both OS and DSS, whereas radiotherapy predicted improved OS (hazard ratio, 0.18; 95% confidence interval, 0.03 to 0.99; P = .049). Conclusions. Age at diagnosis, decade of diagnosis, extent of disease, tumor size, and SES are prognostic factors related to OMM survival. Surgical resection and radiation therapy both improve OMM survival. Practical Implications. Early and detailed examinations for OMM are critical to improving the survival rate in patients with OMM, especially in older patients and patients of lower SES. [ABSTRACT FROM AUTHOR]
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- 2017
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6. Single-step microfluidic synthesis of transferrin-conjugated lipid nanoparticles for siRNA delivery.
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Li, Yujing, Lee, Robert J., Huang, Xueqin, Li, Yuhuan, Lv, Bingcong, Wang, Tianpeng, Qi, Yuhang, Hao, Fei, Lu, Jiahui, Meng, Qingfan, Teng, Lirong, Zhou, Yulin, Xie, Jing, and Teng, Lesheng
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NANOPARTICLES ,TRANSFERRIN ,ACUTE phase proteins ,NANOSTRUCTURED materials ,SMALL interfering RNA - Abstract
Microfluidic systems can accelerate clinical translation of nanoparticles due to their ability to generate nanoparticles in a well-controlled and reproducible manner. In this study, a single-step process based on microfluidic focusing (MF) was employed to synthesize transferrin-conjugated lipid nanoparticles (Tf-LNPs) and the method was compared with a multi-steps bulk mixing (BM) method. The results indicate that this single-step MF process enables rapid and efficient synthesis of Tf-LNPs, which were named Tf-LNPs-MF. Tf-LNPs-MF was shown to have a smaller size and more uniform structures compared to LNPs produced by multi-steps BM method (Tf-LNPs-BM). Furthermore, efficient cellular uptake of Tf-LNPs-MF in vitro as well as greater tumor inhibition in vivo proved that Tf-LNPs-MF had higher siRNA delivery efficiency in vitro and in vivo . Taken together, this single-step microfluidic synthesis significantly simplified the Tf-LNPs production and improved their drug delivery properties and may serve as a valuable tool for developing new cancer therapies. [ABSTRACT FROM AUTHOR]
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- 2017
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7. Cell-Penetrating Peptide and Transferrin Co-Modified Liposomes for Targeted Therapy of Glioma.
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Wang, Xi, Zhao, Yarong, Dong, Shiyan, Lee, Robert J., Yang, Dongsheng, Zhang, Huan, and Teng, Lesheng
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LIPOSOMES ,GLIOMAS ,BLOOD-brain barrier ,CELL-penetrating peptides ,BRAIN tumors ,TRANSFERRIN ,LASER microscopy ,CANCER - Abstract
Glioma is one of the most aggressive and common malignant brain tumors. Due to the presence of the blood-brain barrier (BBB), the effectiveness of therapeutics is greatly affected. In this work, to develop an efficient anti-glioma drug with targeting and which was able to cross the BBB, cell-penetrating peptides (R8) and transferrin co-modified doxorubicin (DOX)-loaded liposomes (Tf-LPs) were prepared. Tf-LPs possessed a spherical shape and uniform size with 128.64 nm and their ξ-potential was 6.81 mV. Tf-LPs were found to be stable in serum within 48 h. Uptake of Tf-LPs in both U87 and GL261 cells was analyzed by confocal laser scanning microscopy and by flow cytometry. Tf-LPs were efficiently taken up by both U87 and GL261 cells. Moreover, Tf-LPs exhibited sustained-release. The cumulative release of DOX from Tf-LPs reached ~50.0% and showed excellent anti-glioma efficacy. Histology of major organs, including brain, heart, liver, spleen, lungs and kidney, and the bodyweight of mice, all indicated low toxicity of Tf-LPs. In conclusion, Tf-LPs showed great promise as an anti-glioma therapeutic agent. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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8. An overview of cancer drugs approved through expedited approval programs and orphan medicine designation globally between 2011 and 2020.
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Wang, Shuhang, Yang, Qiuyan, Deng, Lan, Lei, Qi, Yang, Yuqi, Ma, Peiwen, Men, Yuxin, Yung, Bryant C., Lee, Robert J., Zhang, Mengzi, and Li, Ning
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DRUG approval , *ORPHAN drugs , *DRUG development , *ORPHANS , *DRUG standards - Abstract
• The expedited approval pathways have broadly expanded worldwide. • Overview of the expedited approval programs in China is provided. • Orphan drug designation should be highly valued in drug development for rare disease/tumor. • A great disparity persists on regulatory frameworks across the world in novel drug development. The use of expedited approval pathways for anticancer drug development, which provide the advantages of high efficiency and cost-effectiveness, has expanded significantly in recent years. During the past decade, a total of 410 new molecular entities have been approved by the US Food and Drug Administration (FDA), with a steady growth of 6.5% in the US. In Europe, 9–75% of approved anticancer drugs were granted at least one expedited approval program. Various expedited pathways have also been implemented worldwide to address underrepresented medical needs rapidly. China has adapted several expedited approval programs, including breakthrough therapy designation, priority review, and conditional approval, to keep up with the growth in pharmaceutical development. It is expected that worldwide standards for drug approval will become more standardized in the next decade. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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9. A folate receptor-targeted liposomal formulation for paclitaxel
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Wu, Jun, Liu, Qing, and Lee, Robert J.
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PACLITAXEL , *CYTOPLASM , *CANCER cells , *ANTINEOPLASTIC agents - Abstract
Abstract: A novel liposomal formulation of paclitaxel targeting the folate receptor (FR) was synthesized and characterized. This formulation was designed to overcome vehicle toxicity associated with the traditional Cremophor EL-based formulation and to provide the added advantages of prolonged systemic circulation time and selective targeting of the FR, which is frequently overexpressed on epithelial cancer cells. The formulation had the composition of dipalmitoyl phosphatidylcholine/dimyristoyl phosphatidylglycerol/monomethoxy-polyethylene glycol (PEG)2000-distearoyl phosphatidylethanolamine/folate-PEG3350-distearoyl phosphatidylethanolamine (DPPC/DMPG/mPEG-DSPE/folate-PEG-DSPE) at molar ratios of (85.5:9.5:4.5:0.5) and a drug-to-lipid molar ratio of 1:33. The liposomes were prepared by polycarbonate membrane extrusion. The mean particle size of the liposomes was 97.1nm and remained stable for at least 72h at 4°C. FR-targeted liposomes of the same lipid composition entrapping calcein were shown to be efficiently taken up by KB oral carcinoma cells, which are highly FR+. FR-targeted liposomes containing paclitaxel showed 3.8-fold greater cytotoxicity compared to non-targeted control liposomes in KB cells. Plasma clearance profiles of paclitaxel in the liposomal formulations were then compared to paclitaxel in Cremophor EL formulation. The liposomal formulations showed much longer terminal half-lives (12.33 and 14.23h for FR-targeted and non-targeted liposomes, respectively) than paclitaxel in Cremophor EL (1.78h). In conclusion, the paclitaxel formulation described in this study has substantial stability and favorable pharmacokinetic properties. The FR-targeted paclitaxel formulation is potentially useful for treatment of FR+ tumors and warrants further investigation. [Copyright &y& Elsevier]
- Published
- 2006
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10. Complete regression of xenograft tumors using biodegradable mPEG-PLA-SN38 block copolymer micelles.
- Author
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Lu, Lu, Zheng, Yan, Weng, Shuqiang, Zhu, Wenwei, Chen, Jinhong, Zhang, Xiaomin, Lee, Robert J., Yu, Bo, Jia, Huliang, and Qin, Lunxiu
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XENOGRAFTS , *BIODEGRADABLE materials , *BLOCK copolymers , *ANTINEOPLASTIC agents , *IN vitro studies - Abstract
7-Ethyl-10-hydroxy-comptothecin (SN38) is an active metabolite of irinotecan (CPT-11) and the clinical application of SN38 is limited by its hydrophobicity and instability. To address these issues, a series of novel amphiphilic mPEG-PLA-SN38-conjugates were synthesized by linking SN38 to mPEG-PLA-SA, and they could form micelles by self-assembly. The effects of mPEG-PLA composition were studied in vitro and in vivo. The mean diameters of mPEG 2K -PLA-SN38 micelles and mPEG 4K -PLA-SN38 micelles were 10–20 nm and 120 nm, respectively, and mPEG 2K -PLA-SN38 micelles showed greater antitumor efficacy than mPEG 4K -PLA-SN38 micelles both in vitro and in vivo. These data suggest that the lengths of mPEG and PLA chains had a major impact on the physicochemical characteristics and antitumor activity of SN38-conjugate micelles. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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11. Triggering liposomal drug release with a lysosomotropic agent.
- Author
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Subin Xiong, Hong Li, Bo Yu, Jun Wu, and Lee, Robert J.
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LIPOSOMES , *ENDOSOMES , *ORGANELLES , *CANCER treatment , *TUMORS , *CHLOROQUINE - Abstract
Drug release from liposomes in the endosome-lysosomal organelles into cytoplasm is critical to cytotoxicity and anticancer effects. Chloroquine is a lysosomotropic agent that has been reported to enhance in vitro cytotoxicity of basic anticancer drugs. To investigate the mechanism of chloroquine triggering basic anticancer drugs release from liposomes and the potential to treat solid tumors in clinic, daunorubicin was loaded into folate-targeted liposomes by ammonium sulfate remote loading method. In vitro triggered release profiles showed that chloroquine can instantly expel about 11% daunorubicin out of liposomes. In vitro cytotoxicity of folate-targeted liposomal daunorubicin on L1210JF(FR+) was enhanced by chloroquine, which was further confirmed by confocal micrographs. Intraliposomal pH was increased by adding chloroquine into 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) liposomes with ammonium sulfate gradient, but was not higher than 5.5. Ion exchange and pH rising are the most plausible mechanisms of chloroquine triggering daunorubicin release from liposomes. In vivo anticancer effects on a murine solid tumor model with L1210JF indicated that chloroquine induced daunorubicin release from liposomes as well. Overall, these results support the potential application of chloroquine to trigger the release of liposomal drugs and ultimately to improve the therapeutic efficacy. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:5011-5018, 2010 [ABSTRACT FROM AUTHOR]
- Published
- 2010
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12. Synthesis and evaluation of a novel ligand for folate-mediated targeting liposomes
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Xiang, Guangya, Wu, Jun, Lu, Yanhui, Liu, Zhilan, and Lee, Robert J.
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VITAMIN B complex , *CANCER , *LEUKEMIA , *LIPOSOMES - Abstract
Abstract: Folate receptors (FRs) have been identified as cellular surface markers for cancer and leukemia. Liposomes containing lipophilic derivatives of folate have been shown to effectively target FR-expressing cells. Here, we report the synthesis of a novel lipophilic folate derivative, folate-polyethylene glycol-cholesterol hemisuccinate (F-PEG-CHEMS), and its evaluation as a targeting ligand for liposomal doxorubicin (L-DOX) in FR-expressing cells. Liposomes containing F-PEG-CHEMS, with a mean diameter of 120±20nm, were synthesized by polycarbonate membrane extrusion and were shown to have excellent colloidal stability. The liposomes were taken up selectively by KB cells, which overexpress FR-α. Compared to folate-PEG-cholesterol (F-PEG-Chol), which contains a carbamate linkage, F-PEG-CHEMS better retained its FR-targeting activity during prolonged storage. In addition, F-PEG-CHEMS containing liposomes loaded with DOX (F-L-DOX) showed greater cytotoxicity (IC50 =10.0μM) than non-targeted control L-DOX (IC50 =57.5μM) in KB cells. In ICR mice, both targeted and non-targeted liposomes exhibited long circulation properties, although F-L-DOX (t 1/2 =12.34h) showed more rapid plasma clearance than L-DOX (t 1/2 =17.10h). These results suggest that F-PEG-CHEMS is effective as a novel ligand for the synthesis of FR-targeted liposomes. [Copyright &y& Elsevier]
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- 2008
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13. Cholesterol as a bilayer anchor for PEGylation and targeting ligand in folate-receptor-targeted liposomes.
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Zhao, Xiaobin B., Muthusamy, Natarajan, Byrd, John C., and Lee, Robert J.
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BILAYER lipid membranes , *ISOPENTENOIDS , *STEROLS , *PHOSPHOLIPIDS , *DOXORUBICIN , *LIPOSOMES - Abstract
Phospholipids have been extensively evaluated as an anchor for both PEGylation and receptor-targeting in liposomal formulations. However, cholesterol, another important component in biomembranes, has not been fully investigated as an alternative anchor. In this study, the potential role of cholesterol for anchoring PEG and folate was investigated. Cholesterol derivatives were synthesized for PEGylation (mPEG-cholesterol) and folate receptor (FR) targeting (folate-PEG-cholesterol) and incorporated into the bilayer of FR-targeted liposomal doxorubicin. The colloidal stability of these cholesterol derivative-containing liposomes was superior to non-PEGylated liposomes, indicating that steric barrier provided by mPEG-cholesterol can efficiently inhibit aggregation of liposomes. FR-targeting activity of these liposomes was demonstrated by in vitro cell-binding studies on FR-overexpressing KB cells. In addition, in vivo circulation of cholesterol-anchored liposomes was prolonged compared to non-PEGylated liposomes. These studies suggest that cholesterol is a viable bilayer anchor for synthesis of PEGylated and FR-targeted liposomes. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2424–2435, 2007 [ABSTRACT FROM AUTHOR]
- Published
- 2007
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14. Vascular targeting of doxorubicin using cationic liposomes
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Wu, Jun, Lee, Alice, Lu, Yanhui, and Lee, Robert J.
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DOXORUBICIN , *LIPOSOMES , *DRUG therapy , *CELL-mediated cytotoxicity - Abstract
Abstract: Tumor vessel has been recognized as an important target for anticancer therapy. Cationic liposomes have been shown to selectively target tumor endothelial cells, thus can potentially be used as a carrier for chemotherapy agents. In this study, cationic liposomes containing 20mol% cationic lipid dimethyl dioctadecyl ammonium bromide (DDAB) and loaded with doxorubicin (DOX) were prepared and characterized. The cationic liposomal DOX showed 10.8 and 9.1 times greater cytotoxicity than control PEGylated liposomal DOX in KB oral carcinoma and L1210 murine lymphocytic leukemia cells, and 7.7- and 6.8-fold greater cytotoxicity compared to control neutral non-PEGylated liposomal DOX, repectively, in these two cell lines. Although cationic liposomal DOX had higher tumor accumulation at 30min after intravenous administration compared to control liposomes (p <0.05), DOX uptake of these liposomes at 24h post-injection was similar to that of PEGylated liposomal DOX (p >0.05) and approximately twice the levels of the free drug and non-PEGylated liposomes. In a murine tumor model generated using L1210 cells, increased survival rate was obtained with cationic liposomal DOX treatment compared to free DOX (p <0.01), neutral liposome control (p <0.01), as well as PEGylated liposomes (p <0.05). In conclusion, the cationic liposomal DOX formulation produced superior in vitro cytotoxicity and in vivo antitumor activity, and warrants further investigation. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
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