Liposomal delivery and polyethylene glycol-liposomal oxaliplatin for the treatment of colorectal cancer (Review)

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Abstract

Oxaliplatin is effective for the treatment of advanced colorectal cancer; however, its application is restricted due to its dose-limiting toxicity. Liposomes are sphere-shaped vesicles consisting of one or more phospholipid bilayers. Liposomes as drug carriers are characterized by delayed release, lesion targeting and may be used as a drug-delivery system to decrease the side effects of cytotoxic drugs. Active targeting modification of liposomes may change the biological distribution of the anticancer agents, reduce or reverse multidrug resistance of tumor cells and enhance the effects of anticancer therapy. Based on the characteristics mentioned above, the aim of the present review was to demonstrate that polyethylene glycol-liposomes containing oxaliplatin may offer advantages for the treatment of colorectal cancer in clinical practice.

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Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential

Maria Laura Immordino, Franco Dosio, Luigi Cattel (2006)

Among several promising new drug-delivery systems, liposomes represent an advanced technology to deliver active molecules to the site of action, and at present several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles (“first-generation liposomes”) to “second-generation liposomes”, in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. A significant step in the development of long-circulating liposomes came with inclusion of the synthetic polymer poly-(ethylene glycol) (PEG) in liposome composition. The presence of PEG on the surface of the liposomal carrier has been shown to extend blood-circulation time while reducing mononuclear phagocyte system uptake (stealth liposomes). This technology has resulted in a large number of liposome formulations encapsulating active molecules, with high target efficiency and activity. Further, by synthetic modification of the terminal PEG molecule, stealth liposomes can be actively targeted with monoclonal antibodies or ligands. This review focuses on stealth technology and summarizes pre-clinical and clinical data relating to the principal liposome formulations; it also discusses emerging trends of this promising technology.

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Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect.

H. Maeda, G Y Bharate, J. Daruwalla (2009)

For over half a century extensive research has been undertaken for the control of cancer. However, success has been limited to certain malignancies, and surgical intervention is potentially curative for early stage patients. For the majority of patients with advanced stage of cancer, the treatment is limited to chemotherapy or radiation. Chemotherapy in particular has limitations due to the lack of selectivity with severe toxicity. Under these circumstances tumor-targeted delivery of anticancer drugs is perhaps one of the most important steps for cancer chemotherapy. We reported such a drug for the first time, styrene-maleic acid copolymer-conjugated neocarzinostatin (SMANCS) in 1979, and it eventually led to formulate the concept of the enhanced permeability and retention (EPR) effect of solid tumors in 1986. Monoclonal antibody conjugates are another direction, of which interest is increasing recently though with limited success. The EPR-effect appears as a universal phenomenon in solid tumors which warrants the development of other polymeric drugs or nanomedicine. EPR-effect is applicable for any biocompatible macromolecular compounds above 40 kDa, even larger than 800 kDa, or of the size of bacteria; thus complexed molecules like micelles and liposomes containing anticancer drugs are hallmark examples. The drug concentration in tumor compared to that of the blood (T/B ratio) can be usually as high as 10-30 times. In case of SMANCS/Lipiodol given via tumor feeding artery, the T/B ratio can be as high as 2000, a real pin-point targeting. EPR-effect is not just passive targeting for momentary tumor delivery, but it means prolonged drug retention for more than several weeks or longer. This review describes the pathophysiological mechanisms of the EPR-effect, architectural difference of tumor blood vessel, various factors involved and artificial augmentation of EPR-effect with respect to tumor-selective delivery, and then advantages and problems of macromolecular drugs.

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Enhanced permeability and retention (EPR) effect for anticancer nanomedicine drug targeting.

Khaled Greish (2010)

Effective cancer therapy remains one of the most challenging tasks to the scientific community, with little advancement on overall cancer survival landscape during the last two decades. A major limitation inherent to most conventional anticancer chemotherapeutic agents is their lack of tumor selectivity. One way to achieve selective drug targeting to solid tumors is to exploit abnormalities of tumor vasculature, namely hypervascularization, aberrant vascular architecture, extensive production of vascular permeability factors stimulating extravasation within tumor tissues, and lack of lymphatic drainage. Due to their large size, nano-sized macromolecular anticancer drugs administered intravenously (i.v.) escape renal clearance. Being unable to penetrate through tight endothelial junctions of normal blood vessels, their concentration builds up in the plasma rendering them long plasma half-life. More importantly, they can selectively extravasate in tumor tissues due to its abnormal vascular nature. Overtime the tumor concentration will build up reaching several folds higher than that of the plasma due to lack of efficient lymphatic drainage in solid tumor, an ideal application for EPR-based selective anticancer nanotherapy. Indeed, this selective high local concentration of nano-sized anticancer drugs in tumor tissues has proven superior in therapeutic effect with minimal side effects in both preclinical and clinical settings.

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Author and article information

Journal

Journal ID (nlm-ta): Biomed Rep

Journal ID (iso-abbrev): Biomed Rep

Journal ID (publisher-id): BR

Title: Biomedical Reports

Publisher: D.A. Spandidos

ISSN (Print): 2049-9434

ISSN (Electronic): 2049-9442

Publication date (Print): May 2014

Publication date (Electronic): 12 March 2014

Publication date PMC-release: 12 March 2014

Volume: 2

Issue: 3

Pages: 335-339

Affiliations

[1 ]Department of General Surgery, Third People’s Hospital of Mianyang, Mianyang, Sichuan 621000, P.R. China

[2 ]Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing, Chongqing 400016, P.R. China

Author notes

Correspondence to: Professor Zhong-Xue Fu, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, 1 Friendship Road, Yuzhong District, Chongqing, Chongqing 400016, P.R. China, E-mail: fzx990521@ 123456126.com

Article

Publisher ID: br-02-03-0335

DOI: 10.3892/br.2014.249

PMC ID: 3990200

PubMed ID: 24748970

SO-VID: 2595460d-6039-4d31-87f1-7511f9835dc2

License:

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

Liposomal delivery and polyethylene glycol-liposomal oxaliplatin for the treatment of colorectal cancer (Review)

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RNA drug delivery

Most cited references 62

Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential

Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect.

Enhanced permeability and retention (EPR) effect for anticancer nanomedicine drug targeting.

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