Generic placeholder image

Mini-Reviews in Medicinal Chemistry


ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

New Trends in Liposome-based Drug Delivery in Colorectal Cancer

Author(s): Julia B. Krajewska, Adrian Bartoszek and Jakub Fichna*

Volume 19, Issue 1, 2019

Page: [3 - 11] Pages: 9

DOI: 10.2174/1389557518666180903150928

Price: $65


Colorectal cancer (CRC) is one of the most common cancers in both men and women. Approximately one-third of patients do not survive five years from diagnosis, which indicates the need for treatment improvement, also through new ways of drug delivery. A possible strategy to increase treatment efficacy is the use of liposomal formulation, which allows delivering both hydrophobic and hydrophilic compounds with better biocompatibility and reduced side-effects. Liposomal formulations showed better antitumor activity, longer drug accumulation and no cytotoxic effect on normal cells when compared to free drugs. In this review, we will present liposomal preparations studied in CRC in vitro and in vivo. We will focus on the advantages of liposomal delivery over conventional therapy as well as modifications which increase specificity, drug accumulation and efficacy. Moreover, we will discuss formulations investigated in clinical trials. Liposomal delivery has a great potential in overcoming current limitations of cancer therapy and development of this system gives new perspectives in CRC treatment.

Keywords: Colorectal cancer, liposomes, drug delivery, anticancer treatment, targeted delivery, chemotherapy, oxaliplatin, 5-FU.

Graphical Abstract
Ferlay, J.; Soerjomataram, I.; Ervik, M.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase. No. 11 [Internet].
Howlader, N.; Noone, A.; Krapcho, M.; Miller, D.; Bishop, K.; Kosary, C.; Yu, M.; Ruhl, J.; Tatalovich, Z.; Mariotto, A. SEER Cancer Statistics Review, 1975-2014, National Cancer Institute. Bethesda, MD, Http://Seer.Cancer.Gov/Csr/1975_2014/ Based on November 2016 SEER Data Submission, Posted to the SEER Web Site, April 2017. Http://Seer.Cancer.Gov/Csr/1975_2014/ 2017, pp 1-101.
Zununi Vahed, S.; Salehi, R.; Davaran, S.; Sharifi, S. Liposome-Based Drug Co-Delivery Systems in Cancer Cells. Mater. Sci. Eng. C, 2017, 71, 1327-1341.
Allen, T.M.; Cullis, P.R. Liposomal drug delivery systems: From concept to clinical applications. Adv. Drug Deliv. Rev., 2013, 65(1), 36-48.
Udofot, O.; Affram, K.; Israel, B.; Agyare, E. Cytotoxicity of 5-fluorouracil-loaded ph-sensitive liposomal nanoparticles in colorectal cancer cell lines. Integr. Cancer Sci. Ther., 2015, 2(5), 245-252.
Udofot, O.; Affram, K.; Smith, T.; Tshabe, B.; Krishnan, S.; Sachdeva, M.; Agyare, E. Pharmacokinetic, Biodistribution and therapeutic efficacy of 5-fluorouracil-loaded ph-sensitive pegylated liposomal nanoparticles in HCT-116 tumor bearing mouse. J. Nat. Sci., 2016, 2(1)
Moghimipour, E.; Rezaei, M.; Ramezani, Z.; Kouchak, M.; Amini, M.; Angali, K.A.; Dorkoosh, F.A.; Handali, S. Transferrin targeted liposomal 5-fluorouracil induced apoptosis via mitochondria signaling pathway in cancer cells. Life Sci., 2018, 194, 104-110.
Fanciullino, R.; Giacometti, S.; Mercier, C.; Aubert, C.; Blanquicett, C.; Piccerelle, P.; Ciccolini, J. In Vitro and in vivo Reversal of resistance to 5-Fluorouracil in colorectal cancer cells with a novel stealth double-liposomal formulation. Br. J. Cancer, 2007, 97(7), 919-926.
Fanciullino, R.; Mollard, S.; Giacometti, S.; Berda-Haddad, Y.; Chefrour, M.; Aubert, C.; Iliadis, A.; Ciccolini, J. In Vitro and in vivo Evaluation of lipofufol, a new triple stealth liposomal formulation of modulated 5-Fu: Impact on efficacy and toxicity. Pharm. Res., 2013, 30(5), 1281-1290.
Hare, J.I.; Neijzen, R.W.; Anantha, M.; Dos Santos, N.; Harasym, N.; Webb, M.S.; Allen, T.M.; Bally, M.B.; Waterhouse, D.N. Treatment of colorectal cancer using a combination of liposomal irinotecan (Irinophore CTM) and 5-Fluorouracil. PLoS One, 2013, 8(4), e62349.
Zhang, B.; Wang, T.; Yang, S.; Xiao, Y.; Song, Y.; Zhang, N.; Garg, S. Development and evaluation of oxaliplatin and irinotecan co-loaded liposomes for enhanced colorectal cancer therapy. J. Control. Release, 2016, 238, 10-21.
Yang, C.; Fu, Z-X. PEG-Liposomal oxaliplatin combined with nuclear factor-κb inhibitor (pdtc) induces apoptosis in human colorectal cancer cells. Oncol. Rep., 2014, 32(4), 1617-1621.
Li, K. ZHOU, Z.-Y.; JI, P.-P.; LUO, H.-S. Knockdown of β-Catenin by SiRNA influences proliferation, apoptosis and invasion of the colon cancer cell line SW480. Oncol. Lett., 2016, 11(6), 3896-3900.
Bochicchio, S.; Dapas, B.; Russo, I.; Ciacci, C.; Piazza, O.; De Smedt, S.; Pottie, E.; Barba, A.A.; Grassi, G. In vitro and Ex vivo Delivery of tailored SiRNA-nanoliposomes for E2F1 silencing as a potential therapy for colorectal cancer. Int. J. Pharm., 2017, 525(2), 377-387.
Mamot, C.; Ritschard, R.; Wicki, A.; Küng, W.; Schuller, J.; Herrmann, R.; Rochlitz, C. Immunoliposomal delivery of doxorubicin can overcome multidrug resistance mechanisms in EGFR- Overexpressing tumor cells. J. Drug Target., 2012, 20(5), 422-432.
Zalba, S.; Contreras, A.M.; Haeri, A.; ten Hagen, T.L.M.; Navarro, I.; Koning, G.; Garrido, M.J. Cetuximab-Oxaliplatin-Liposomes for epidermal growth factor receptor targeted chemotherapy of colorectal cancer. J. Control. Release, 2015, 210, 26-38.
Garg, A.; Kokkoli, E. PH-Sensitive PEGylated liposomes functionalized with a fibronectin-mimetic peptide show enhanced intracellular delivery to colon cancer cell. Curr. Pharm. Biotechnol., 2011, 12(8), 1135-1143.
Oku, N.; Asai, T.; Watanabe, K.; Kuromi, K.; Nagatsuka, M.; Kurohane, K.; Kikkawa, H.; Ogino, K.; Tanaka, M.; Ishikawa, D.; Tsukada, H.; Momose, M.; Nakayama, J.; Taki, T. Anti-Neovascular therapy using novel peptides homing to angiogenic vessels. Oncogene, 2002, 21(17), 2662-2669.
Asai, T.; Shimizu, K.; Kondo, M.; Kuromi, K.; Watanabe, K.; Ogino, K.; Taki, T.; Shuto, S.; Matsuda, A.; Oku, N. Anti-Neovascular therapy by liposomal DPP-CNDAC targeted to angiogenic vessels. FEBS Lett., 2002, 520(1-3), 167-170.
Maeda, N.; Takeuchi, Y.; Takada, M.; Sadzuka, Y.; Namba, Y.; Oku, N. Anti-neovascular therapy by use of tumor neovasculature-targeted long-circulating liposome. J. Control. Release, 2004, 100(1), 41-52.
Shimizu, K.; Asai, T.; Fuse, C.; Sadzuka, Y.; Sonobe, T.; Ogino, K.; Taki, T.; Tanaka, T.; Oku, N. Applicability of anti-neovascular therapy to drug-resistant tumor: suppression of drug-resistant P388 tumor growth with neovessel-targeted liposomal adriamycin. Int. J. Pharm., 2005, 296(1-2), 133-141.
Asai, T.; Miyazawa, S.; Maeda, N.; Hatanaka, K.; Katanasaka, Y.; Shimizu, K.; Shuto, S.; Oku, N. Antineovascular therapy with angiogenic vessel-targeted polyethyleneglycol-shielded liposomal DPP-CNDAC. Cancer Sci., 2008, 99(5), 1029-1033.
Schiffelers, R.M.; Koning, G.A.; Ten Hagen, T.L.M.; Fens, M.H.A.M.; Schraa, A.J.; Janssen, A.P.C.A.; Kok, R.J.; Molema, G.; Storm, G. Anti-Tumor efficacy of tumor vasculature-targeted liposomal doxorubicin. J. Control. Release, 2003, 91(1-2), 115-122.
Shibuya, M.; Claesson-Welsh, L. Signal Transduction by VEGF Receptors in Regulation of Angiogenesis and Lymphangiogenesis. Exp. Cell Res., 2006, 312(5), 549-560.
Wicki, A.; Rochlitz, C.; Orleth, A.; Ritschard, R.; Albrecht, I.; Herrmann, R.; Christofori, G.; Mamot, C. Targeting tumor-associated endothelial cells: anti-vegfr2 immunoliposomes mediate tumor vessel disruption and inhibit tumor growth. Clin. Cancer Res., 2012, 18(2), 454-464.
Song, Z.; Lin, Y.; Zhang, X.; Feng, C.; Lu, Y.; Gao, Y.; Dong, C.; Cyclic, R.G.D. Peptide-Modified liposomal drug delivery system for targeted oral apatinib administration: Enhanced cellular uptake and improved therapeutic effects. Int. J. Nanomedicine, 2017, 12, 1941-1958.
Crosasso, P.; Brusa, P.; Dosio, F.; Arpicco, S.; Pacchioni, D.; Schuber, F.; Cattel, L. Antitumoral activity of liposomes and immunoliposomes containing 5- fluorouridine prodrugs. J. Pharm. Sci., 1997, 86(7), 832-839.
Hosokawa, S.; Tagawa, T.; Niki, H.; Hirakawa, Y.; Nohga, K.; Nagaike, K. Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner. Br. J. Cancer, 2003, 89(8), 1545-1551.
Hamaguchi, T.; Matsumura, Y.; Nakanishi, Y.; Muro, K.; Yamada, Y.; Shimada, Y.; Shirao, K.; Niki, H.; Hosokawa, S.; Tagawa, T.; Kakizoe, T. Antitumor effect of MCC-465, pegylated liposomal doxorubicin tagged with newly developed monoclonal antibody gah, in colorectal cancer xenografts. Cancer Sci., 2004, 95(7), 608-613.
Lee, C.M.; Tanaka, T.; Murai, T.; Kondo, M.; Kimura, J.; Su, W.; Kitagawa, T.; Ito, T.; Matsuda, H.; Miyasaka, M. Novel chondroitin sulfate-binding cationic liposomes loaded with cisplatin efficiently suppress the local growth and liver metastasis of tumor cells in vivo. Cancer Res., 2002, 62(15), 4282-4288.
Kawakami, K.; Puri, R.K.; Kawakami, M. Overexpressed cell surface interleukin-4 receptor molecules can be successfully targeted for antitumor cytotoxin therapy. Crit. Rev. Immunol., 2001, 21(1-3), 12.
Koller, F.L.; Hwang, D.G.; Dozier, E.A.; Fingleton, B. Epithelial interleukin-4 receptor expression promotes colon tumor growth. Carcinogenesis, 2010, 31(6), 1010-1017.
Yang, C.; Liu, H.; Tsai, Y.; Tseng, J.; Liang, S.; Chen, C.; Lian, W.; Wei, M.; Lu, M.; Lu, R. Doxorubicin as a model for enhancing cellular uptake and antitumor efficacy in murine colorectal cancer interleukin-4 receptor-targeted liposomal doxorubicin as a model for enhancing cellular uptake and antitumor ef fi cacy in murine colorectal cancer. Cancer Biol. Ther., 2015, 4047, 1641-1650.
Bansal, D.; Gulbake, A.; Tiwari, J.; Jain, S.K. Development of liposomes entrapped in alginate beads for the treatment of colorectal cancer. Int. J. Biol. Macromol., 2016, 82, 687-695.
Fang, T.; Dong, Y.; Zhang, X.; Xie, K.; Lin, L.; Wang, H. Integrating a novel SN38 prodrug into the pegylated liposomal system as a robust platform for efficient cancer therapy in solid tumors. Int. J. Pharm., 2016, 512(1), 39-48.
Blocker, S.J.; Douglas, K.A.; Polin, L.A.; Lee, H.; Hendriks, B.S.; Lalo, E.; Chen, W.; Shields, A.F. Liposomal64Cu-PET imaging of anti-vegf drug effects on liposomal delivery to colon cancer xenografts. Theranostics, 2017, 7(17), 4229-4239.
Riahi, M.M.; Sahebkar, A.; Sadri, K.; Nikoofal-Sahlabadi, S.; Jaafari, M.R. Stable and Sustained Release Liposomal formulations of celecoxib: in vitro and in vivo anti-tumor evaluation. Int. J. Pharm., 2018, 540(1-2), 89-97.
Sun, D.; Zhao, L.; Lin, J.; Zhao, Y.; Zheng, Y. Cationic liposome Co-encapsulation of SMAC mimetic and ZVAD using a novel lipid bilayer fusion loaded with mlkl-pdna for tumour inhibition in vivo. J. Drug Target., 2018, 26(1), 45-54.
Peng, P.C.; Hong, R.L.; Tsai, Y.J.; Li, P.T.; Tsai, T.; Chen, C.T. Dual-effect liposomes encapsulated with doxorubicin and chlorin E6 augment the therapeutic effect of tumor treatment. Lasers Surg. Med., 2015, 47(1), 77-87.
Kang, X.J.; Wang, H.Y.; Peng, H.G.; Chen, B.F.; Zhang, W.Y.; Wu, A.H.; Xu, Q.; Huang, Y.Z. Codelivery of dihydroartemisinin and doxorubicin in mannosylated liposomes for Drug-resistant colon cancer therapy. Acta Pharmacol. Sin., 2017, 38(6), 885-896.
Kokuryo, D.; Aoki, I.; Yuba, E.; Kono, K.; Aoshima, S.; Kershaw, J.; Saga, T. Evaluation of a combination tumor treatment using thermo-triggered liposomal drug delivery and carbon ion irradiation. Transl. Res., 2017, 185, 24-33.
Jeong, H.S.; Hwang, H.; Oh, P.S.; Kim, E.M.; Lee, T.K.; Kim, M.; Kim, H.S.; Lim, S.T.; Sohn, M.H.; Jeong, H.J. Effect of high-intensity focused ultrasound on drug release from doxorubicin-loaded PEGylated liposomes and therapeutic effect in colorectal cancer murine models. Ultrasound Med. Biol., 2016, 42(4), 947-955.
Riviere, K.; Kieler-Ferguson, H.M.; Jerger, K.; Szoka, F.C. Anti-tumor activity of liposome encapsulated fluoroorotic acid as a single agent and in combination with liposome irinotecan. J. Control. Release, 2011, 153(3), 288-296.
Shimizu, T.; Abu Lila, A.S.; Nishio, M.; Doi, Y.; Ando, H.; Ukawa, M.; Ishima, Y.; Ishida, T. Modulation of antitumor immunity contributes to the enhanced therapeutic efficacy of liposomal oxaliplatin in mouse model. Cancer Sci., 2017, 108(9), 1864-1869.
Brody, L.P.; Sahuri-Arisoylu, M.; Parkinson, J.R.; Parkes, H.G.; So, P.W.; Hajji, N.; Thomas, E.; Frost, G.S.; Miller, A.D.; Bell, J.D. Cationic Lipid-Based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects. Int. J. Nanomedicine, 2017, 12, 6677-6685.
Ichihara, H.; Nakagawa, S.; Matsuoka, Y.; Yoshida, K.; Matsumoto, Y.; Ueoka, R. Nanotherapy with hybrid liposomes for colorectal cancer along with apoptosis in vitro and in vivo. Anticancer Res., 2014, 34(9), 4701-4708.
Liposomal SN-38 in Treating Patients With Metastatic Colorectal Cancer. NCT00311610 (accessed Apr 14, 2018).
Celator Pharmaceuticals. Multicenter Study Of CPX-1 (Irinotecan HCl: Floxuridine) Liposome Injection In Patients With Advanced Colorectal Cancer. NCT00361842 (accessed Apr 14, 2018).
GERCOR. Liposome-encapsulated irinotecan hydrochloride PEP02 or irinotecan hydrochloride, leucovorin calcium, and fluorouracil as second-line therapy in treating patients with metastatic colorectal cancer (PEPCOL). NCT01375816 (accessed Apr 14, 2018).
Phase 2 Study of Thermodox as Adjuvant Therapy With Thermal Ablation (RFA) in Treatment of Metastatic Colorectal Cancer(mCRC). NCT01464593 (accessed Apr 14, 2018).
Phase I and Pharmacokinetic Study of Biweekly PEP02 in mCRC Refractory to 1st-line Oxaliplatin Base Therapy. NCT00940758 (accessed Apr 14, 2018).
Intravenously Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PROMITIL) in Cancer Patients With Solid Tumors. NCT01705002 (accessed Apr 14, 2018).
A Safety and Effectiveness Study of Aroplatin in Patients With Advanced Colorectal Cancer Resistant to Standard Therapies. NCT00043199 (accessed Apr 14, 2018).
Aroplatin and Capecitabine in Patients With Advanced Colorectal Cancer Resistant to Standard Therapies. NCT00081536 (accessed Apr 14, 2018).
Liposomal Irinotecan, Fluorouracil, Leucovorin Calcium, and Rucaparib in Treating Patients With Metastatic Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer. NCT03337087 (accessed Apr 14, 2018).
The Effect of Exparel on Post Operative Pain and Narcotic Use After Colon Surgery. NCT02052557 show/NCT02052557 (accessed Apr 14, 2018).
A Safety and Effectiveness Study of Aroplatin in Patients With Advanced Solid Malignancies. NCT00057395 https://clinicaltrials. gov/ct2/show/NCT00057395 (accessed Apr 14, 2018).
TAS102 in Combination With NAL-IRI in Advanced GI Cancers. NCT03368963 (accessed Apr 14, 2018).
Batist, G.; Gelmon, K.A.; Chi, K.N.; Miller, W.H.; Chia, S.K.L.; Mayer, L.D.; Swenson, C.E.; Janoff, A.S.; Louie, A.C. Safety, Pharmacokinetics, and efficacy of CPX-1 liposome injection in patients with advanced solid tumors. Clin. Cancer Res., 2009, 15(2), 692-700.
Stathopoulos, G.P.; Boulikas, T.; Kourvetaris, A.; Stathopoulos, J. Liposomal oxaliplatin in the treatment of advanced cancer: A phase I study. Anticancer Res., 2006, 26(2B), 1489-1493.
Beutel, G. Phase I study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor in patients with refractory solid tumors. Clin. Cancer Res., 2005, 11(15), 5487-5495.
Falk, S.; Anthoney, A.; Eatock, M.; Van Cutsem, E.; Chick, J.; Glen, H.; Valle, J.W.; Drolet, D.W.; Albert, D.; Ferry, D. Ajani. J. Multicentre phase II pharmacokinetic and pharmacodynamic study of osi-7904l in previously untreated patients with advanced gastric or gastroesophageal junction adenocarcinoma. Br. J. Cancer, 2006, 95(4), 450-456.
Suenaga, M.; Mizunuma, N.; Matsusaka, S.; Shinozaki, E.; Ozaka, M.; Ogura, M.; Yamaguchi, T. Phase II study of reintroduction of oxaliplatin for advanced colorectal cancer in patients previously treated with oxaliplatin and irinotecan: RE-OPEN study. Drug Des. Devel. Ther., 2015, 9, 3099-3108.
Clamp, A.R.; Schöffski, P.; Valle, J.W.; Wilson, R.H.; Marreaud, S.; Govaerts, A.S.; Debois, M.; Lacombe, D.; Twelves, C.; Chick, J. A Phase I and pharmacokinetic study of OSI-7904L, a liposomal thymidylate synthase inhibitor in combination with oxaliplatin in patients with advanced colorectal cancer. Cancer Chemother. Pharmacol., 2008, 61(4), 579-585.
Golan, T.; Grenader, T.; Ohana, P.; Amitay, Y.; Shmeeda, H.; La-Beck, N.M.; Tahover, E.; Berger, R.; Gabizon, A.A. Pegylated liposomal mitomycin c prodrug enhances tolerance of mitomycin C: A phase 1 study in advanced solid tumor patients. Cancer Med., 2015, 4(10), 1472-1483.
Shields, A.F.; Lange, L.M.; Zalupski, M.M. Phase II study of liposomal doxorubicin in patients with advanced colorectal cancer. Am. J. Clin. Oncol., 2001, 24(1), 96-98.
Eckardt, J.R.; Campbell, E.; Burris, H.A.; Weiss, G.R.; Rodriguez, G.I.; Fields, S.M.; Thurman, A.M.; Peacock, N.W.; Cobb, P.; Rothenberg, M.L. A phase II trial of daunoxome, liposome-encapsulated daunorubicin, in patients with metastatic adeno-carcinoma of the colon. Am. J. Clin. Oncol., 1994, 17(6), 498-501.
Dragovich, T.; Mendelson, D.; Kurtin, S.; Richardson, K.; Von Hoff, D.; Hoos, A. A phase 2 trial of the liposomal dach platinum L-NDDP in patients with therapy-refractory advanced colorectal cancer. Cancer Chemother. Pharmacol., 2006, 58(6), 759-764.
Gentile, E.; Cilurzo, F.; Di Marzio, L.; Carafa, M.; Anna Ventura, C.; Wolfram, J.; Paolino, D.; Celia, C. Liposomal Chemotherapeutics. Future Oncol., 2013, 9(12), 1849-1859.
Tila, D.; Ghasemi, S.; Yazdani-Arazi, S.N.; Ghanbarzadeh, S. Functional liposomes in the cancer-targeted drug delivery. J. Biomater. Appl., 2015, 30(1), 3-16.
Sercombe, L.; Veerati, T.; Moheimani, F.; Wu, S.Y.; Sood, A.K.; Hua, S. Advances and challenges of liposome assisted drug delivery. Front. Pharmacol., 2015, 6, 1-13.

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy