Liposome based delivery systems in pancreatic cancer treatment: from bench to bedside.

Despite rapid advances in cancer diagnosis and treatment, pancreatic cancer remains one of the most difficult human malignancies to be treated, with a mortality rate nearly equal to its incidence. Although gemcitabine has been established as the standard first-line treatment for advanced pancreatic cancer, gemcitabine-based combination chemotherapy showed either marginal or no improvement in survival. Developments in liposomal delivery systems have facilitated the targeting of specific agents for cancer treatment. Such systems could be developed as platforms for future multi-functional theranostic nanodevices tailor-made for the combined detection of early cancer and functional drug delivery. We systemically review liposome based drug-delivery systems, which can provide improved pharmacokinetics, reduced side effects and potentially increased tumor uptake, for pancreatic cancer therapy. Novel liposomal formulations allowing for higher tumor targeting efficiencies and used in current clinical trials to treat this challenging disease are emphasized.

[1]  H. Kantarjian,et al.  Liposomal vincristine in relapsed non-Hodgkin's lymphomas: early results of an ongoing phase II trial. , 2000, Annals of oncology : official journal of the European Society for Medical Oncology.

[2]  A. Mukherjee,et al.  Liposomal Doxorubicin in Breast Cancer , 2007, Women's health.

[3]  Sadik Esener,et al.  Magnetic resonance and fluorescence imaging of doxorubicin-loaded nanoparticles using a novel in vivo model. , 2010, Nanomedicine : nanotechnology, biology, and medicine.

[4]  Teruhiko Yoshida,et al.  Polyethylenimine-mediated gene transfer into pancreatic tumor dissemination in the murine peritoneal cavity , 2001, Gene Therapy.

[5]  Bo Zhang,et al.  Carbon nanotubes in cancer diagnosis and therapy. , 2010, Biochimica et biophysica acta.

[6]  J. Huwyler,et al.  Brain drug delivery of small molecules using immunoliposomes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[7]  B. Wiedenmann,et al.  The Targeted Immunocytokine L19-IL2 Efficiently Inhibits the Growth of Orthotopic Pancreatic Cancer , 2008, Clinical Cancer Research.

[8]  Hiroyuki Honda,et al.  Selective hyperthermia using magnetoliposomes to target cervical lymph node metastasis in a rabbit tongue tumor model , 2003, Cancer science.

[9]  K. B. Garbutcheon-Singh,et al.  Advances in platinum chemotherapeutics. , 2010, Chemistry.

[10]  K. Gelmon,et al.  Phase I study of liposomal vincristine. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  R. Labianca,et al.  Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  A. Gabizon,et al.  Polyethylene Glycol-Coated (Pegylated) Liposomal Doxorubicin , 2012, Drugs.

[13]  T. Boulikas,et al.  Liposomal cisplatin combined with gemcitabine in pretreated advanced pancreatic cancer patients: a phase I-II study. , 2006, Oncology reports.

[14]  R. Kurzrock,et al.  Determination of minimum effective dose and optimal dosing schedule for liposomal curcumin in a xenograft human pancreatic cancer model. , 2009, Anticancer research.

[15]  C. Dass,et al.  Recent developments in liposomes, microparticles and nanoparticles for protein and peptide drug delivery , 2010, Peptides.

[16]  G. Stathopoulos.  Liposomal cisplatin: a new cisplatin formulation , 2010, Anti-cancer drugs.

[17]  Leaf Huang,et al.  Gene therapy progress and prospects: non-viral gene therapy by systemic delivery , 2006, Gene Therapy.

[18]  Jinming Gao,et al.  Theranostic nanomedicine for cancer. , 2008, Nanomedicine.

[19]  Qi Zhou,et al.  Chemically Modified Short Interfering Hybrids (siHYBRIDS): Nanoimmunoliposome Delivery In Vitro and In Vivo for RNAi of HER-2 , 2006, Nucleosides, nucleotides & nucleic acids.

[20]  C. Kosmas,et al.  Phase II study of liposomal cisplatin (Lipoplatin) plus gemcitabine versus cisplatin plus gemcitabine as first line treatment in inoperable (stage IIIB/IV) non-small cell lung cancer. , 2010, Lung cancer.

[21]  Qi Zhou,et al.  Materializing the potential of small interfering RNA via a tumor-targeting nanodelivery system. , 2007, Cancer research.

[22]  Feng Yang,et al.  Effect of multiple‐phase regional intra‐arterial infusion chemotherapy on patients with resectable pancreatic head adenocarcinoma , 2009, Chinese medical journal.

[23]  C. Unger,et al.  Liposomal gemcitabine (GemLip)—efficient drug against hormone‐refractory Du145 and PC‐3 prostate cancer xenografts , 2009, The Prostate.

[24]  C. Mohanty,et al.  Curcumin-encapsulated MePEG/PCL diblock copolymeric micelles: a novel controlled delivery vehicle for cancer therapy. , 2010, Nanomedicine.

[25]  N. Oku,et al.  Effective tumor regression by anti-neovascular therapy in hypovascular orthotopic pancreatic tumor model. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[26]  D. Boturyn,et al.  Tumor targeting with RGD peptide ligands-design of new molecular conjugates for imaging and therapy of cancers. , 2007, Anti-cancer agents in medicinal chemistry.

[27]  Q. Pankhurst,et al.  Imaging applications of nanotechnology in cancer , 2009, Targeted Oncology.

[28]  T. Boulikas,et al.  Liposomal oxaliplatin in the treatment of advanced cancer: a phase I study. , 2006, Anticancer research.

[29]  C. Unger,et al.  Anti-metastatic effects of liposomal gemcitabine in a human orthotopic LNCaP prostate cancer xenograft model , 2009, Clinical & Experimental Metastasis.

[30]  Feng Yang,et al.  Aberrant Hepatic Artery in Patients Undergoing Pancreaticoduodenectomy , 2008, Pancreatology.

[31]  R. Barth,et al.  Boron neutron capture therapy of EGFR or EGFRvIII positive gliomas using either boronated monoclonal antibodies or epidermal growth factor as molecular targeting agents. , 2009, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[32]  Deepak Kumar,et al.  Antisense oligonucleotides: target validation and development of systemically delivered therapeutic nanoparticles. , 2007, Methods in molecular biology.

[33]  H. Nariuchi,et al.  Application of boronated anti-CEA immunoliposome to tumour cell growth inhibition in in vitro boron neutron capture therapy model. , 1991, British Journal of Cancer.

[34]  K. Harrington.  Liposomal cancer chemotherapy: current clinical applications and future prospects , 2001, Expert opinion on investigational drugs.

[35]  H. Yanagie,et al.  Inhibition of human pancreatic cancer growth in nude mice by boron neutron capture therapy. , 1997, British Journal of Cancer.

[36]  M. Moore,et al.  Advanced pancreatic carcinoma: current treatment and future challenges , 2010, Nature Reviews Clinical Oncology.

[37]  R. Labianca,et al.  Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  R. Hofheinz,et al.  Pegylated liposomal doxorubicin in combination with mitomycin C, infusional 5-fluorouracil and sodium folinic acid. A phase-I-study in patients with upper gastrointestinal cancer , 2004, British Journal of Cancer.

[39]  P. Tassone,et al.  In vivo activity of gemcitabine-loaded PEGylated small unilamellar liposomes against pancreatic cancer , 2009, Cancer Chemotherapy and Pharmacology.

[40]  Jiang Long,et al.  Magnetic lymphatic targeting drug delivery system using carbon nanotubes. , 2008, Medical hypotheses.

[41]  G. Schuch.  EndoTAG-1. MediGene. , 2005, Current opinion in investigational drugs.

[42]  R. B. Campbell,et al.  Conjugation of bevacizumab to cationic liposomes enhances their tumor-targeting potential. , 2010, Nanomedicine.

[43]  M. Dellian,et al.  Vascular targeting by EndoTAG™‐1 enhances therapeutic efficacy of conventional chemotherapy in lung and pancreatic cancer , 2010, International journal of cancer.

[44]  A. Masamune,et al.  Fibrinogen induces cytokine and collagen production in pancreatic stellate cells , 2008, Gut.

[45]  G. Schwartz,et al.  A phase II trial of Doxorubicin HCl Liposome Injection in patients with advanced pancreatic adenocarcinoma , 2007, Investigational New Drugs.

[46]  Dong Yang,et al.  Pilot study of targeting magnetic carbon nanotubes to lymph nodes. , 2009, Nanomedicine.

[47]  T. Boulikas.  Clinical overview on Lipoplatin™: a successful liposomal formulation of cisplatin , 2009, Expert opinion on investigational drugs.

[48]  S. Ran,et al.  Increased exposure of anionic phospholipids on the surface of tumor blood vessels. , 2002, Cancer research.

[49]  T. Keck,et al.  A new liposomal formulation of Gemcitabine is active in an orthotopic mouse model of pancreatic cancer accessible to bioluminescence imaging , 2008, Cancer Chemotherapy and Pharmacology.

[50]  W. Hop,et al.  Adjuvant Intra-Arterial Chemotherapy and Radiotherapy Versus Surgery Alone in Resectable Pancreatic and Periampullary Cancer: A Prospective Randomized Controlled Trial , 2008, Annals of surgery.

[51]  Q. Yao,et al.  Targeted drug delivery in pancreatic cancer. , 2010, Biochimica et biophysica acta.

[52]  V. Torchilin.  Antibody-modified liposomes for cancer chemotherapy , 2008, Expert opinion on drug delivery.

[53]  Joseph M. DeSimone,et al.  Strategies in the design of nanoparticles for therapeutic applications , 2010, Nature Reviews Drug Discovery.

[54]  D. Matei,et al.  Pegylated liposomal doxorubicin in ovarian cancer , 2009, Therapeutics and clinical risk management.

[55]  G. Kazemier,et al.  Quality of life after adjuvant intra‐arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer , 2010, Cancer.

[56]  B. Wiedenmann,et al.  Atu027, a liposomal small interfering RNA formulation targeting protein kinase N3, inhibits cancer progression. , 2008, Cancer research.

[57]  T. Boulikas,et al.  Pharmacokinetics and adverse reactions of a new liposomal cisplatin (Lipoplatin): phase I study. , 2005, Oncology reports.

[58]  P. Couvreur,et al.  Liposomal squalenoyl-gemcitabine: formulation, characterization and anticancer activity evaluation. , 2010, Nanoscale.

[59]  Y. Matsumura.  Polymeric micellar delivery systems in oncology. , 2008, Japanese journal of clinical oncology.

[60]  C. Unger,et al.  Antimetastatic Effects of Liposomal Gemcitabine and Empty Liposomes in an Orthotopic Mouse Model of Pancreatic Cancer , 2009, Pancreas.

[61]  G. Anderson,et al.  Southwest Oncology Group Trial S9912: intraperitoneal cisplatin and paclitaxel plus intravenous paclitaxel and pegylated liposomal doxorubicin as primary chemotherapy of small-volume residual stage III ovarian cancer. , 2009, Gynecologic oncology.

[62]  A. Dritschilo,et al.  Combination with liposome-entrapped, ends-modified raf antisense oligonucleotide (LErafAON) improves the anti-tumor efficacies of cisplatin, epirubicin, mitoxantrone, docetaxel and gemcitabine , 2004, Anti-cancer drugs.

[63]  A. Jemal,et al.  Cancer Statistics, 2009 , 2009, CA: a cancer journal for clinicians.

[64]  Zhuo Georgia Chen,et al.  Advances of cancer therapy by nanotechnology. , 2009, Cancer research and treatment : official journal of Korean Cancer Association.

[65]  D. Carbonaro,et al.  Preclinical safety, pharmacokinetics and antitumor efficacy profile of liposome-entrapped SN-38 formulation. , 2005, Anticancer research.

[66]  Q. Ping,et al.  Octreotide-modification enhances the delivery and targeting of doxorubicin-loaded liposomes to somatostatin receptors expressing tumor in vitro and in vivo , 2010, Nanotechnology.

[67]  Jiang Long,et al.  Hydrophilic multi-walled carbon nanotubes decorated with magnetite nanoparticles as lymphatic targeted drug delivery vehicles. , 2009, Chemical communications.

[68]  L. Bi,et al.  Protein chip for detection of DNA mutations. , 2007, Methods in molecular biology.

[69]  M. S. Muthu,et al.  Targeted nanomedicines: effective treatment modalities for cancer, AIDS and brain disorders. , 2009, Nanomedicine.

[70]  S. Akaishi,et al.  Targeting chemotherapy using antibody-combined liposome against human pancreatic cancer cell-line. , 1995, The Tohoku journal of experimental medicine.

[71]  M. Moeschberger,et al.  Molecular Targeting and Treatment of Composite EGFR and EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibodies , 2008, Clinical Cancer Research.

[72]  P. Uster,et al.  Tumour uptake of doxorubicin in polyethylene glycol-coated liposomes and therapeutic effect against a xenografted human pancreatic carcinoma. , 1997, British Journal of Cancer.

[73]  R. Barth.  Boron neutron capture therapy at the crossroads: challenges and opportunities. , 2009, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[74]  Shonagh Walker,et al.  The status of platinum anticancer drugs in the clinic and in clinical trials. , 2010, Dalton transactions.

[75]  S. Halford,et al.  A phase II study evaluating the tolerability and efficacy of CAELYX (liposomal doxorubicin, Doxil) in the treatment of unresectable pancreatic carcinoma. , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.

[76]  M. Marangolo,et al.  Lipoplatin™ Monotherapy: A Phase II Trial of Second-Line Treatment of Metastatic Non-Small-Cell Lung Cancer , 2009, Journal of chemotherapy.

[77]  Y. Oh,et al.  Antitumor activity of EGFR targeted pH-sensitive immunoliposomes encapsulating gemcitabine in A549 xenograft nude mice. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[78]  Guido Bocci,et al.  Drug distribution in tumors: Mechanisms, role in drug resistance, and methods for modification , 2007, Current oncology reports.

[79]  M. Mizuno,et al.  Growth inhibition of human pancreatic cancer cells by human interferon-beta gene combined with gemcitabine. , 2005, International journal of molecular medicine.

[80]  A. Gabizon,et al.  Clinical pharmacology of liposomal anthracyclines: focus on pegylated liposomal Doxorubicin. , 2008, Clinical lymphoma & myeloma.

[81]  R. B. Campbell,et al.  Fighting cancer: from the bench to bedside using second generation cationic liposomal therapeutics. , 2009, Journal of pharmaceutical sciences.

[82]  A. Giatromanolaki,et al.  Concurrent liposomal cisplatin (Lipoplatin), 5-fluorouracil and radiotherapy for the treatment of locally advanced gastric cancer: a phase I/II study. , 2010, International journal of radiation oncology, biology, physics.

[83]  Ji Li,et al.  Potential role of soluble VEGFR-1 in antiangiogenesis therapy for cancer , 2011, Expert review of anticancer therapy.

[84]  P. Choong,et al.  Selective gene delivery for cancer therapy using cationic liposomes: in vivo proof of applicability. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[85]  T. Ishida,et al.  Accelerated clearance of a second injection of PEGylated liposomes in mice. , 2003, International journal of pharmaceutics.

[86]  L. Cattel,et al.  Antitumor activity and pharmacokinetics of liposomes containing lipophilic gemcitabine prodrugs. , 2007, Anticancer research.

[87]  R. Schwendener,et al.  Cytotoxic targeting of F9 teratocarcinoma tumours with anti-ED-B fibronectin scFv antibody modified liposomes , 2002, British Journal of Cancer.

[88]  A. Charonis,et al.  Anionic sites in basement membranes. Differences in their electrostatic properties in continuous and fenestrated capillaries. , 1983, Microvascular research.

[89]  Razelle Kurzrock,et al.  Liposome‐encapsulated curcumin , 2005, Cancer.

[90]  R. Campbell,et al.  Development of 5-FU and Doxorubicin-Loaded Cationic Liposomes against Human Pancreatic Cancer: Implications for Tumor Vascular Targeting , 2006, Pharmaceutical Research.

[91]  S. Filetti,et al.  Gemcitabine-loaded PEGylated unilamellar liposomes vs GEMZAR: biodistribution, pharmacokinetic features and in vivo antitumor activity. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[92]  R. Brand,et al.  Chemoprevention strategies for pancreatic cancer , 2010, Nature Reviews Gastroenterology &Hepatology.

[93]  V. Torchilin.  Recent advances with liposomes as pharmaceutical carriers , 2005, Nature Reviews Drug Discovery.

[94]  M. Piccart,et al.  A randomised phase II study of two different schedules of pegylated liposomal doxorubicin in metastatic breast cancer (EORTC-10993). , 2006, European journal of cancer.

[95]  Qi Zhou,et al.  Tumor-targeting nanoimmunoliposome complex for short interfering RNA delivery. , 2005, Human gene therapy.

[96]  Liposomal cisplatin dose escalation for determining the maximum tolerated dose and dose-limiting toxicity: a phase I study. , 2010, Anticancer research.

[97]  Douglas B. Evans,et al.  Cancer-associated stromal fibroblasts promote pancreatic tumor progression. , 2008, Cancer research.

[98]  M. Mano,et al.  Cationic liposomes for gene delivery , 2005, Expert opinion on drug delivery.