Liposomal drug formulations in cancer therapy: 15 years along the road

Slingerland, Marije; Guchelaar, Henk‐Jan; Gelderblom, Hans

doi:10.1016/j.drudis.2011.09.015

Cited by 233 publications

(142 citation statements)

References 51 publications

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“…Typical examples include liposomal paclitaxel (PTX; Lipusu ® ), 6 doxorubicin (Myocet ® ), daunorubicin (DaunoXome ® ), and cytarabine (DepoCyt ® ). 3 However, the capture of systemically administered nanoparticles by the reticuloendothelial system (RES), which results in rapid clearance from body, remains one of the major drawbacks in drug delivery. This can be overcome by modifying the nanoparticles with flexible hydrophilic polymers such as polyethylene glycol (PEG), as the PEG chains can form a hydrophilic corona surrounding the nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

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Poly(ethylene glycol)-block-poly(ε-caprolactone)– and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

Li¹,

He²,

Su³

et al. 2015

IJN

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Background Effective anticancer drug delivery to the tumor site without rapid body clearance is a prerequisite for successful chemotherapy. 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-N-(methoxy[polyethyleneglycol]-2000) (DSPE-PEG2000) has been widely used in the preparation of stealth liposomes. Although PEG chains can efficiently preserve liposomes from rapid clearance by the reticuloendothelial system (RES), its application has been hindered by poor cellular uptake and unsatisfactory therapeutic effect. Methods To address the dilemma, we presented a facile approach to fabricate novel stealth nanoparticles generated by poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG- b -PCL), soybean phosphatidylcholine (SPC), and cholesterol, namely LPPs (L represented lipid and PP represented PEG- b -PCL), for the delivery of anticancer drug paclitaxel (PTX). LPPs were prepared using the thin film hydration method. Two PEG- b -PCL polymers with different molecular weights (MW; PEG2000-b-PCL2000, MW: 4,000 Da and PEG5000-b-PCL5000, MW: 10,000 Da) were used to fabricate stealth nanoparticles. Conventional PEGylated liposome (LDP2000, L represented lipid and DP2000 represented DSPE-PEG2000) composed of SPC, cholesterol, and DSPE-PEG2000 was used as the control. The physical properties, cellular uptake, endocytosis pathway, cytotoxicity, pharmacokinetics, tumor accumulation, and anticancer efficacy of free PTX, PTX-loaded LPPs, and LDP2000 were systemically investigated after injection into 4T1 breast tumor–bearing mice. Results LPPs were vesicles around 100 nm in size with negative zeta potential. With enhanced stability, LPPs achieved sustainable release of cancer therapeutics. The cellular uptake level was closely related to the PEG chain length of PEG- b -PCL; a shorter PEG chain resulted in higher cellular uptake. Moreover, the cellular internalization of LPP2000 modified by PEG2000- b -PCL2000 on 4T1 cells was 2.1-fold higher than LDP2000 due to the improved stability of LPP2000. The cytotoxicity of PTX-loaded LPP2000 was also higher than that of LDP2000 and LPP5000 as observed using a WST-8 assay, while blank LPPs showed negligible toxicity. Consistent with the results of the in vitro study, in vivo experiments showed that LPPs allowed significantly improved bioavailability and prolonged T 1/2β as compared to free PTX injection. More importantly, LPPs mainly accumulated at the tumor site, probably due to the enhanced permeation and retention effect (EPR effect). As a nanomedicine, LPP2000 (tumor inhibition rate of 75.1%) significantly enhanced the therapeutic effect of PTX in 4T1 breast tumor–bearing mice by inhibiting tumor growth compared to LDP2000 and LPP5000 (tumor inhibition rates of 56.3% and 49.5%, respectively). Conclusion Modification of li...

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Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5] So far, several liposomal anticancer drugs have been approved by the US Food and Drug Administration (FDA) and become commercially available on the market. Typical examples include liposomal paclitaxel (PTX; Lipusu ® ), 6 doxorubicin (Myocet ® ), daunorubicin (DaunoXome ® ), and cytarabine (DepoCyt ® ).…”

Section: Introductionmentioning

confidence: 99%

Poly(ethylene glycol)-block-poly(ε-caprolactone)– and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

Li¹,

He²,

Su³

et al. 2015

IJN

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“…[7][8][9] Liposomes have been widely used as nanosize carriers in drug delivery systems for tumor therapy. 10 It is well known that pegylated liposomes can spontaneously accumulate in solid tumors via an enhanced permeability and retention effect through a passive targeting mechanism. 11 In fact, the ability to control and produce a burst release of the encapsulated drug from liposomes would be extremely advantageous and may prove to be an essential step in providing effective levels of drug in the tumor.…”

Section: Introductionmentioning

confidence: 99%

The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo

Wang¹,

Wang²,

Zhong³

et al. 2015

IJN

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Clotted plasma proteins are present on the walls of tumor vessels and in tumor stroma. Tumor-homing peptide Cys-Arg-Glu-Lys-Ala (CREKA) could recognize the clotted plasma proteins in tumor vessels. Thermosensitive liposomes could immediately release the encapsulated drug in the vasculature of the heated tumor. In this study, we designed a novel form of targeted thermosensitive liposomes, CREKA-modified lysolipid-containing thermosensitive liposomes (LTSLs), containing doxorubicin (DOX) (DOX-LTSL-CREKA), to investigate the hypothesis that DOX-LTSL-CREKA might target the clotted plasma proteins in tumor vessels as well as tumor stroma and then exhibit burst release of the encapsulated DOX at the heated tumor site. We also hypothesized that the high local drug concentration produced by these thermosensitive liposomes after local hyperthermia treatment will be useful for treatment of multidrug resistance. The multidrug-resistant human breast adenocarcinoma (MCF-7/ADR) cell line was chosen as a tumor cell model, and the targeting and immediate release characteristics of DOX-LTSL-CREKA were investigated in vitro and in vivo. Furthermore, the antitumor activity of DOX-LTSL-CREKA was evaluated in MCF-7/ADR tumor-bearing nude mice in vivo. The targeting effect of the CREKA-modified thermosensitive liposomes on the clotted plasma proteins was confirmed in our in vivo imaging and immunohistochemistry experiments. The burst release of this delivery system was observed in our in vitro temperature-triggered DOX release and flow cytometry analysis and also by confocal microscopy experiments. The antitumor activity of the DOX-LTSL-CREKA was confirmed in tumor-bearing nude mice in vivo. Our findings suggest that the combination of targeting the clotted plasma proteins in the tumor vessel wall as well as tumor stroma by using CREKA peptide and temperature-triggered drug release from liposomes by using thermosensitive liposomes offers an attractive strategy for chemotherapeutic drug delivery to tumors.

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“…104,105 Membrane-permeable drugs are preferentially chosen for liposomal delivery systems because these drugs are capable of passing through the plasma membrane of the targeted tumor cells. 106 However, this type of drug inevitably reaches the circulatory system, enters normal cells and leads to cytotoxicity to normal organs.…”

Section: Llo-based Immunotoxin/immunoliposome For Killing Tumor Cellsmentioning

confidence: 99%

Listeriolysin O as a strong immunogenic molecule for the development of new anti-tumor vaccines

Sun

Liu

2013

Human Vaccines & Immunotherapeutics

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Liposomal drug formulations in cancer therapy: 15 years along the road

Cited by 233 publications

References 51 publications

Poly(ethylene glycol)-block-poly(ε-caprolactone)– and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

Poly(ethylene glycol)-block-poly(ε-caprolactone)– and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo

Listeriolysin O as a strong immunogenic molecule for the development of new anti-tumor vaccines

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Liposomal drug formulations in cancer therapy: 15 years along the road

Cited by 233 publications

References 51 publications

Poly(ethylene glycol)-block-poly(&epsilon;-caprolactone)&ndash; and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

Poly(ethylene glycol)-block-poly(&epsilon;-caprolactone)&ndash; and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo

Listeriolysin O as a strong immunogenic molecule for the development of new anti-tumor vaccines

Contact Info

Product

Resources

About

Poly(ethylene glycol)-block-poly(ε-caprolactone)– and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

Poly(ethylene glycol)-block-poly(ε-caprolactone)– and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery