• MARILENE ESTANQUEIRO Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Portugal
  • MARIA HELENA AMARAL Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Portugal
  • JAIME CONCEICAO Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Portugal
  • JOSE MANUEL SOUSA LOBO Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Portugal


Cancer, Drug delivery, Liposomes, Liposomes derivatives, Special liposomes


Most current anticancer agents are present lack of specificity, leading to systemic toxicity and adverse effects, and limiting the maximum dose of drug. Liposomes quickly passed from a simple scientific curiosity to magic bullets†for the delivery of drugs. Liposomal formulations of anticancer drugs have been extensively evaluated, with notorious advances and the market introduction of some of them. In the last years, the research under liposomes has been carried out to increase the circulation time and the specificity to cancer cells. The aim of this work was to make a review about the research carried out about the application of liposomes as carriers for anticancer drugs. Liposomal formulations of anticancer drugs have been extensively evaluated. However, many other liposome based carriers were studied, like immuno liposomes, thermossensitive liposomes, dual functional liposomes and cross linked multifunctional liposomes, intended to increase drug specificity. Additionally, some special types of liposomes, like niosomes, transfersomes and ethosomes were also investigated as cytotoxic drug carriers.


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Defining Cancer. National Cancer Institute at the National Institutes of Health National Cancer Institute at the National Institutes of Health; 2013. Available from: http://www. cancer.gov/cancertopics/cancerlibrary/what-is-cancer [Last accessed on 2013 Dec 02].

GLOBOCAN: Estimated Cancer Incidence, Mortality and Prevalence Worldwide. World Health Organization/ International Agency for Research on Cancer; 2014. Available from: http://globocan. iarc.fr/Default.aspx [Last accessed on 2014 Apr 13].

Brizel DM, Albers ME, Fisher SR, Scher RL, Richtsmeier WJ, Hars V, et al. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 1998;338:1798-804.

Chaplin DJ, Hill SA, Bell KM, Tozer GM. Modification of tumor blood flow: Current status and future directions. Seminars Radiation Oncol 1998;8:151-63.

Needham D, Dewhirst MW. The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors. Adv Drug Delivery Rev 2001;53:285-305.

Jain RK. Barriers to drug delivery in solid tumors. Sci Am 1994;271:58-65.

Yuan F. Transvascular drug delivery in solid tumors. Seminars Radiation Oncol 1998;8:164-75.

Kong G, Anyarambhatla G, Petros WP, Braun RD, Colvin OM, Needham D, et al. Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release. Cancer Res 2000;60:6950-57.

Needham D. Materials engineering of lipid bilayers for drug carrier performance. MRS Bull 1999;24:32-41.

Aderem A, Underhill DM. Mechanisms of phagocytosis in macrophages. Annu Rev Immunol 1999;17:593-623.

Yoo JW, Doshi N, Mitragotri S. Adaptive micro and nanoparticles: Temporal control over carrier properties to facilitate drug delivery. Adv Drug Delivery Rev 2011;63:1247-56.

Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev 2001;53:283-318.

Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Ipe BI, et al. Renal clearance of quantum dots. Nat Biotechnol 2007;25:1165-78.

Rejman J, Oberle V, Zuhorn IS, Hoekstra D. Size-dependent internalization of particles via the pathways of clathrin-and caveolae-mediated endocytosis. Biochem J 2004;377:159-69.

Laverman P, Boerman OC, Oyen WJG, Dams ETM, Storm G, Corstens FHM. Liposomes for scintigraphic detection of infection and inflammation. Adv Drug Delivery Rev 1999;37:225-35.

Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 1986;46:6387-92.

Cho K, Wang X, Nie S, Chen ZG, Shin DM. Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 2008;14:1310-6.

Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 2005;5:161-71.

Fang J, Nakamura H, Maeda H. The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Delivery Rev 2011;63:136-51.

Allen TM. Liposomes: opportunities in drug delivery. Drugs 1997;54:8-14.

Lasic DD. Novel applications of liposomes. Trends Biotechnol 1998;16:307-21.

P Torchilin V. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discovery 2005;4:145-60.

Sandip BT, Udupa N, Rao BSS, Devi PU. Thermosensitive liposomes and localised hyperthermia-an effective bimodality approach for tumour management. Indian J Pharmacol 2000;32:214-20.

Verma RK, Garg S. Drug delivery technologies and future directions. Pharm Technol 2001;25:1-14.

Edwards KA, Baeumner AJ. Liposomes in analyses. Talanta 2006;68:1421-31.

Park J. Liposome-based drug delivery in breast cancer treatment. Breast Cancer Res 2002;4:95-9.

Drummond DC, Noble CO, Hayes ME, Park JW, Kirpotin DB. Pharmacokinetics and in vivo drug release rates in liposomal nanocarrier development. J Pharm Sci 2008;97:4696-740.

Moutinho C, Matos C, Balcão V. Development of innovative nanotechnology-based drug delivery systems for cancer therapy. Revista FCS-UFP 2007;4:94-104.

Oberoi HS, Nukolova NV, Kabanov AV, Bronich TK. Nanocarriers for delivery of platinum anticancer drugs. Adv Drug Delivery Rev 2013;65:1667-85.

Vemuri S, Rhodes CT. Preparation and characterization of liposomes as therapeutic delivery systems: a review. Pharm Acta Helv 1995;70:95-111.

Marianecci C, Di Marzio L, Rinaldi F, Celia C, Paolino D, Alhaique F, et al. Niosomes from 80s to present: the state of the art. Adv Colloid Interface Sci 2014;205:187-206.

Sharma A, Sharma US. Liposomes in drug delivery: progress and limitations. Int J Pharm 1997;154:123-40.

Yarosh DB. Liposomes in investigative dermatology. Photodermatol Photoimmunol Photomed 2001;17:203-12.

Zuidam NJ, Gouw HKME, Barenholz Y, Crommelin DJA. Physical (in) stability of liposomes upon chemical hydrolysis: the role of lysophospholipids and fatty acids. Biochim Biophys Acta 1995;1240:101-10.

Hwang KJ. Liposome pharmacokinetics. In: Ostro MJ. ed. Liposome from Biophysics to Therapeutics. New York: Marcel Dekker Inc; 1987. p. 109–56.

Senior JH. Fate and behavior of liposomes in vivo: a review of controlling factors. Crit Rev Ther Drug Carrier Syst 1987;3:123-93.

Maruyama K, Ishida O, Takizawa T, Moribe K. Possibility of active targeting to tumor tissues with liposomes. Adv Drug Delivery Rev 1999;40:89-102.

Wu NZ, Da D, Rudoll TL, Needham D, Whorton AR, Dewhirst MW. Increased microvascular permeability contributes to preferential accumulation of Stealth liposomes in tumor tissue. Cancer Res 1993;53:3765-70.

Gabizon AA. Stealth liposomes and tumor targeting: one step further in the quest for the magic bullet. Clin Cancer Res 2001;7:223-5.

O'Shaughnessy JA. Pegylated liposomal doxorubicin in the treatment of breast cancer. Clin Breast Cancer 2003;4:318-28.

Gabizon AA. Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy. Cancer Invest 2001;19:424-36.

Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science 2004;303:1818-22.

Laginha KM, Verwoert S, Charrois GJ, Allen TM. Determination of doxorubicin levels in whole tumor and tumor nuclei in murine breast cancer tumors. Clin Cancer Res 2005;11:6944-9.

Al-Jamal WT, Al-Ahmady ZS, Kostarelos K. Pharmacokinetics and tissue distribution of temperature-sensitive liposomal doxorubicin in tumor-bearing mice triggered with mild hyperthermia. Biomaterials 2012;33:4608-17.

Van Lummel M, Van Blitterswijk WJ, Vink SR, Veldman RJ, Van der Valk MA, Schipper D, et al. Enriching lipid nanovesicles with short-chain glucosylceramide improves doxorubicin delivery and efficacy in solid tumors. FASEB J 2011;25:280-9.

Barenholz Y. Doxil® — The first FDA-approved nano-drug: lessons learned. J Controlled Release 2012;160:117-34.

Dass CR, Walker TL, Burton MA, Decruz EE. Enhanced anticancer therapy mediated by specialized liposomes. J Pharm Pharmacol 1997;49:972-5.

Derksen JTP, Morselt HWM, Scherphof GL. Uptake and processing of immunoglobulin-coated liposomes by subpopulations of rat liver macrophages. Biochim Biophys Acta 1988;971:127-36.

Maruyama K, Holmberg E, Kennel SJ, Klibanov A, Torchilin VP, Huang L. Characterization of in vivo immunoliposome targeting to pulmonary endothelium. J Pharm Sci 1990;79:978-84.

Torchilin VP, Klibanov AL, Huang L, O'Donnell S, Nossiff ND, Khaw BA. Targeted accumulation of polyethylene glycol-coated immunoliposomes in infarcted rabbit myocardium. FASEB J 1992;6:2716-9.

Torchilin VP. Immunoliposomes and PEGylated Immunoliposomes: possible use for targeted delivery of imaging agents. Immunomethods 1994;4:244-58.

Torchilin VP, Narula J, Halpern E, Khaw BA. Poly(ethylene glycol)-coated anti-cardiac myosin immunoliposomes: factors influencing targeted accumulation in the infarcted myocardium. Biochim Biophys Acta 1996;1279:75-83.

Torchilin V. Antibody-modified liposomes for cancer chemotherapy. Expert Opin Drug Delivery 2008;5:1003-25.

Koshkaryev A, Sawant R, Deshpande M, Torchilin V. Immunoconjugates and long circulating systems: Origins, current state of the art and future directions. Adv Drug Delivery Rev 2013;65:24-35.

Duggan S, Keating G. Pegylated liposomal doxorubicin. Drugs 2011;71:2531-58.

Park JW, Hong K, Carter P, Asgari H, Guo LY, Keller GA, et al. Development of anti-p185HER2 immunoliposomes for cancer therapy. Proc Natl Acad Sci U S A 1995;92:1327-31.

Park JW, Hong K, Kirpotin DB, Colbern G, Shalaby R, Baselga J, et al. Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery. Clin Cancer Res 2002;8:1172-81.

Park JW, Kirpotin DB, Hong K, Shalaby R, Shao Y, Nielsen UB, et al. Tumor targeting using anti-her2 immunoliposomes. J Controlled Release 2001;74:95-113.

Shmeeda H, Tzemach D, Mak L, Gabizon A. Her2-targeted pegylated liposomal doxorubicin: retention of target-specific binding and cytotoxicity after in vivo passage. J Controlled Release 2009;136:155-60.

Cheng WWK, Allen TM. Targeted delivery of anti-CD19 liposomal doxorubicin in B-cell lymphoma: a comparison of whole monoclonal antibody, Fab′ fragments and single chain Fv. J Controlled Release 2008;126:50-8.

Allen TM, Mumbengegwi DR, Charrois GJR. Anti-CD19-targeted liposomal doxorubicin improves the therapeutic efficacy in murine B-cell lymphoma and ameliorates the toxicity of liposomes with varying drug release rates. Clin Cancer Res 2005;11:3567-73.

Kirpotin DB, Drummond DC, Shao Y, Shalaby MR, Hong K, Nielsen UB, et al. Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res 2006;66:6732-40.

Sapra P, Allen TM. Improved outcome when B-Cell lymphoma is treated with combinations of immunoliposomal anticancer drugs targeted to both the CD19 and CD20 epitopes. Clin Cancer Res 2004;10:2530-7.

Lopus M. Antibody-DM1 conjugates as cancer therapeutics. Cancer Lett 2011;307:113-8.

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;89:1545–51.

Allen TM. Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer 2002;2:750–63.

Needham D, Anyarambhatla G, Kong G, Dewhirst MW. A new temperature-sensitive liposome for use with mild hyperthermia: characterization and testing in a human tumor xenograft model. Cancer Res 2000;60:1197-201.

Zhu L, Huo Z, Wang L, Tong X, Xiao Y, Ni K. Targeted delivery of methotrexate to skeletal muscular tissue by thermosensitive magnetoliposomes. Int J Pharm 2009;370:136-43.

Alexiou C, Arnold W, Klein RJ, Parak FG, Hulin P, Bergemann C, et al. Locoregional cancer treatment with magnetic drug targeting. Cancer Res 2000;60:6641-8.

Schroeder A, Honen R, Turjeman K, Gabizon A, Kost J, Barenholz Y. Ultrasound triggered release of cisplatin from liposomes in murine tumors. J. Controlled Release 2009;137:63-8.

Koning G, Eggermont AM, Lindner L, Hagen TM. Hyperthermia and thermosensitive liposomes for improved delivery of chemotherapeutic drugs to solid tumors. Pharm Res 2010;27:1750-4.

Yatvin MB, Weinstein JN, Dennis WH, Blumenthal R. Design of liposomes for enhanced local release of drugs by hyperthermia. Science 1978;202:1290-3.

Gaber MH, Wu NZ, Hong K, Huang SK, Dewhirst MW, Papahadjopoulos D. Thermosensitive liposomes: extravasation and release of contents in tumor microvascular networks. Int J Radiat Oncol Biol Phys 1996;36:1177-87.

Torchilin VP. Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J 2007;9:E128-47.

Torchilin VP. Multifunctional nanocarriers. Adv Drug Delivery Rev 2006;58:1532-55.

Basel MT, Shrestha TB, Troyer DL, Bossmann SH. Protease-sensitive, Polymer-caged liposomes: a method for making highly targeted liposomes using triggered release. ACS Nano 2011;5:2162-75.

Hällbrink M, Florén A, Elmquist A, Pooga M, Bartfai T, Langel Ü. Cargo delivery kinetics of cell-penetrating peptides. Biochim Biophys Acta 2001;1515:101-9.

Frankel AD, Pabo CO. Cellular uptake of the tat protein from human immunodeficiency virus. Cell 1988;55:1189-93.

Torchilin VP, Rammohan R, Weissig V, Levchenko TS. TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors. Proc Natl Acad Sci U S A 2001;98:8786-91.

Tachibana R, Harashima H, Shono M, Azumano M, Niwa M, Futaki S, et al. Intracellular regulation of macromolecules using ph-sensitive liposomes and nuclear localization signal: qualitative and quantitative evaluation of intracellular trafficking. Biochem Biophys Res Commun 1998;251:538-44.

Jiang T, Zhang Z, Zhang Y, Lv H, Zhou J, Li C, et al. Dual-functional liposomes based on pH-responsive cell-penetrating peptide and hyaluronic acid for tumor-targeted anticancer drug delivery. Biomaterials 2012;33:9246-58.

Cheng CJ, Saltzman WM. Enhanced siRNA delivery into cells by exploiting the synergy between targeting ligands and cell-penetrating peptides. Biomaterials 2011;32:6194-203.

Lee JY, Bae KH, Kim JS, Nam YS, Park TG. Intracellular delivery of paclitaxel using oil-free, shell cross-linked HSA--multi-armed PEG nanocapsules. Biomaterials 2011;32:8635-44.

Liu J, Zhao Y, Guo Q, Wang Z, Wang H, Yang Y, et al. TAT-modified nanosilver for combating multidrug-resistant cancer. Biomaterials 2012;33:6155-61.

Koren E, Apte A, Sawant RR, Grunwald J, Torchilin VP. Cell-penetrating TAT peptide in drug delivery systems: Proteolytic stability requirements. Drug Delivery 2011;18:377-84.

Eliyahu H, Servel N, Domb AJ, Barenholz Y. Lipoplex-induced hemagglutination: potential involvement in intravenous gene delivery. Gene Ther 2002;9:850-8.

Li S, Tseng WC, Stolz DB, Wu SP, Watkins SC, Huang L. Dynamic changes in the characteristics of cationic lipidic vectors after exposure to mouse serum: implications for intravenous lipofection. Gene Ther 1999;6:585-94.

Fischer D, Li Y, Ahlemeyer B, Krieglstein J, Kissel T. In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials 2003;24:1121-31.

Crawford J. Clinical uses of pegylated pharmaceuticals in oncology. Cancer Treat Rev 2002;28:7-11.

Lee ES, Gao Z, Kim D, Park K, Kwon IC, Bae YH. Super pH-sensitive multifunctional polymeric micelle for tumor pHe specific TAT exposure and multidrug resistance. J Controlled Release 2008;129:228-36.

Koren E, Apte A, Jani A, Torchilin VP. Multifunctional PEGylated 2C5-immunoliposomes containing pH-sensitive bonds and TAT peptide for enhanced tumor cell internalization and cytotoxicity. J Controlled Release 2012;160:264-73.

Sethuraman VA, Bae YH. TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors. J Controlled Release 2007;118:216-24.

Joo K-I, Xiao L, Liu S, Liu Y, Lee C-L, Conti PS, et al. Crosslinked multilamellar liposomes for controlled delivery of anticancer drugs. Biomaterials 2013;34:3098-4109.

Uchegbu IF, Florence AT. Non-ionic surfactant vesicles (niosomes): Physical and pharmaceutical chemistry. Adv Colloid Interface Sci 1995;58:1-55.

Farkas E, Schubert R, Zelkó R. Effect of β-sitosterol on the characteristics of vesicular gels containing chlorhexidine. Int J Pharm 2004;278:63-70.

Bajaj A, Desai M. Challenges and strategies in novel drug delivery technologies. Pharm Times 2006;38:12-6.

Wadhe K, Kalsait R, Umekar M. Alternate drug delivery system: recent advancement and future challenges. Arch Pharm Sci Res 2009;1:97–105.

Mahale NB, Thakkar PD, Mali RG, Walunj DR, Chaudhari SR. Niosomes: novel sustained release nonionic stable vesicular systems-An overview. Adv Colloid Interface Sci 2012;183–184:46-54.

Jiao J. Polyoxyethylated nonionic surfactants and their applications in topical ocular drug delivery. Adv Drug Delivery Rev 2008;60:1663-73.

Zografi G. Interfacial phenomena. In: Gennaro AR. ed. Remington: the science and practice of pharmacy. 17 ed. Pennsylvania: Mark Publishing; 1995. p. 241-51.

Kumar GP, Rajeshwarrao P. Nonionic surfactant vesicular systems for effective drug delivery-an overview. Acta Pharm Sin B 2011;1:208-19.

Kong M, Park H, Feng C, Hou L, Cheng X, Chen X. Construction of hyaluronic acid noisome as functional transdermal nanocarrier for tumor therapy. Carbohydr Polym 2013;94:634-41.

Tavano L, Vivacqua M, Carito V, Muzzalupo R, Caroleo MC, Nicoletta F. Doxorubicin loaded magneto-niosomes for targeted drug delivery. Colloids Surf B 2013;102:803-7.

Paolino D, Cosco D, Muzzalupo R, Trapasso E, Picci N, Fresta M. Innovative bola-surfactant niosomes as topical delivery systems of 5-fluorouracil for the treatment of skin cancer. Int J Pharm 2008;353:233-42.

Cevc G, Blume G. Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. Biochim Biophys Acta 1992;1104:226-32.

Honeywell-Nguyen PL, Bouwstra JA. Vesicles as a tool for transdermal and dermal delivery. Drug Discovery Today Technol 2005;2:67-74.

Cevc G. Transfersomes, liposomes and other lipid suspensions on the skin: Permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit Rev Ther Drug Carrier Syst 1996;13:257-388.

Trotta M, Peira E, Carlotti ME, Gallarate M. Deformable liposomes for dermal administration of methotrexate. Int J Pharm 2004;270:119-25.

El Maghraby GMM, Williams AC, Barry BW. Skin delivery of oestradiol from deformable and traditional liposomes: Mechanistic studies. J Pharm Pharmacol 1999;51:1123-34.

Cevc G, Schätzlein A, Richardsen H. Ultradeformable lipid vesicles can penetrate the skin and other semi-permeable barriers unfragmented. Evidence from double label CLSM experiments and direct size measurements. Biochim Biophys Acta 2002;1564:21-30.

El Maghraby GMM, Williams AC, Barry BW. Skin delivery of 5-fluorouracil from ultradeformable and standard liposomes in-vitro. J Pharm Pharmacol 2001;53:1069-77.

Lau KG, Chopra S, Maitani Y. Entrapment of bleomycin in ultra-deformable liposomes. STP Pharma Sci 2003;13:237-9.

Hiruta Y, Hattori Y, Kawano K, Obata Y, Maitani Y. Novel ultra-deformable vesicles entrapped with bleomycin and enhanced to penetrate rat skin. J Controlled Release 2006;113:146-54.

Maheshwari RGS, Tekade RK, Sharma PA, Darwhekar G, Tyagi A, Patel RP, et al. Ethosomes and ultradeformable liposomes for transdermal delivery of clotrimazole: a comparative assessment. Saudi Pharm J 2012;20:161-70.

Merdan V, Alhaique F, Touitou E. Vesicular carriers for topical delivery. Acta Technol Legis Med 1998;12:1-6.

Berner B, Liu P. Alcohols: In: Smith EW, Maibach HI. (eds) CRC Press: Percutaneous Penetration Enhancers Boca Raton; 1995. p. 45-60.

Barry BW. Is transdermal drug delivery research still important today? Drug Discovery Today 2001;6:967-71.

Paolino D, Celia C, Trapasso E, Cilurzo F, Fresta M. Paclitaxel-loaded ethosomes®: Potential treatment of squamous cell carcinoma, a malignant transformation of actinic keratoses. Eur J Pharm Biopharm 2012;81:102-12.



How to Cite

ESTANQUEIRO, M., M. H. AMARAL, J. CONCEICAO, and J. M. S. LOBO. “EVOLUTION OF LIPOSOMAL CARRIERS INTENDED TO ANTICANCER DRUG DELIVERY: AN OVERVIEW”. International Journal of Current Pharmaceutical Research, vol. 7, no. 4, Oct. 2015, pp. 26-33, https://innovareacademics.in/journals/index.php/ijcpr/article/view/9535.



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