Portal de Periódicos da CAPES

Nanopharmacology of Liposomes Developed for Cancer Therapy

2010; Future Medicine; Volume: 5; Issue: 7 Linguagem: Inglês

10.2217/nnm.10.75

1748-6963

Madaswamy S. Muthu, Si‐Shen Feng,

Monoclonal and Polyclonal Antibodies Research

NanomedicineVol. 5, No. 7 EditorialFree AccessNanopharmacology of liposomes developed for cancer therapyMadaswamy S Muthu and Si-Shen FengMadaswamy S Muthu† Author for correspondenceDepartment of Chemical & Biomolecular Engineering, National University of Singapore, Block E5, 02–11, 4 Engineering Drive 4, Singapore 117576, Singapore. and Si-Shen FengDepartment of Chemical & Biomolecular Engineering, National University of Singapore, Block E4, 05–12, 4 Engineering Drive 4, Singapore 117576, SingaporePublished Online:27 Sep 2010https://doi.org/10.2217/nnm.10.75AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: efficacyliposomesmarketed formulationssafetyAlthough the last decade has seen unprecedented advances in cancer diagnosis and therapy, for many patients, cancer remains a chronic and debilitating disease. Cancer is the second most common disease that leads to death worldwide, and the concerns associated with conventional therapy/delivery systems initiated research into novel drug-delivery systems for suitable anticancer drugs. These drugs are well known for their serious dose-related side effects owing to their uncontrolled pharmacokinetics (mainly poor biodistribution) and lack of targeting effects in the body [1,2]. Multidrug resistance is another major problem in cancer drug delivery [2]. Therefore, novel drug delivery systems developed based on nanotechnology concepts such as liposomes can improve future cancer therapy.Nanopharmacology of liposomes involves the use of nanoliposomes with novel pharmacological principles, such as favorable pharmacokinetics, to maximize efficacy and minimize the adverse effects of drugs, including drug delivery to targeted locations or tissues (e.g., cancer cells). Liposomes are lipid bilayer vesicles that were first prepared in the 1960s [3]. Liposomes can be seen as the simplest artificial biological cells, which have potential applications in drug delivery, gene therapy and artificial blood, as well as being used as a model of biological cell and cell membrane [4]. Liposomes are usually composed of phospholipids or cholesterol, which are used to encapsulate various active drugs. Liposomes may vary in size; most are 200 nm or smaller – these can be termed 'nanoliposomes'. However, there is a size limitation for liposomes. Liposomal formulation is similar to that of a small section of a circular lipid bilayer. During the formulation process, it must sacrifice its edge energy in order to overcome the bending resistance; thus, liposomes cannot be made as small as would be desired. If the circular section of bilayer is too small, it would not have enough edge energy to provide the necessary bending energy [5]. Liposomes are a promising dosage form/drug delivery system owing to their size, hydrophobic and hydrophilic character, biocompatibility, biodegradability, low toxicity and immunogenicity [6,7]. Indeed, liposome products were the first nanopharmaceuticals approved by the US FDA and are listed in the database of dosage forms with a FDA code of 852 [101]. Stealth liposomes are an emerging novel development in the technology to enhance their half-life in the bloodstream. Generally, the surfaces of these liposomes are modified with the attachment of polyethylene glycol (PEG) groups to the liposomal bilayer to avoid the opsonization process [8].From a nanopharmacological view, by entering directly into the central compartment and distributing the drug to cancer tissues, liposomal cancer therapies represent an additional compartment model in the pharmacokinetic model. However, the tissue distribution patterns are dependent on the type of liposome formulation. Generally, the maximum amount of drug is rapidly released from liposomes into the central compartment for therapy, before the liposomes are cleared by the mononuclear phagocyte system. Surface modification of liposomes slows mononuclear phagocyte system uptake, thereby retaining drug-loaded liposomes in the plasma and enabling prolonged circulation, extravasation in tissues, preferential uptake at the endothelium and subsequent drug release in the tissue compartment [102].Currently, various liposomes are being intensively developed as nanoformulations and have been shown to considerably reduce the toxicity of anticancer drugs with significant efficacy. The nanopharmacology and current clinical study highlights of the liposomes that have been encapsulated with anticancer drugs, such as doxorubicin, daunorubicin, cisplatin, paclitaxel and vincristine, are covered in this article.Marketed nanoliposome formulationsDoxil® (Sequus Pharmaceuticals, Menlo Park, CA, USA), a long-acting PEGylated liposomal product of doxorubicin, was developed with a diameter smaller than 100 nm and demonstrated significant improvements over free doxorubicin, with greater efficacy and lower cardiotoxicity. Doxil is used to treat cancer in Kaposi's sarcoma and multiple myeloma. The improvements are attributed to passive targeting of tumors, due to leaky tumor vasculature and enhanced permeation and retention, and to lower concentrations of free doxorubicin at healthy tissue sites. Pharmacological evidence suggests that liposomal Doxil is metabolized by leukemia cells via a different mechanism than that for free doxorubicin, which might explain the improved efficacy and lower toxicity. Furthermore, Doxil is currently undergoing clinical trials for the treatment of breast cancer [6]. Ogawara and colleagues have recently investigated the effect of PEGylated liposomal doxorubicin (Doxil) in a male mouse tumor model inoculated with either colon cancer (C26) cells or their doxorubicin-resistant (multidrug resistant) subclone, which overexpresses P-gp efflux pumps [9]. The results demonstrated that Doxil had anticancer effects on both doxorubicin-resistant and non-doxorubicin-resistant C26 cells. However, hand–foot syndrome was a dose-limiting toxic effect of Doxil. This adverse effect was not observed with the use of doxorubicin alone. A reason for this unexpected toxic effect of Doxil could be a considerable amount of drug being delivered to the skin owing to the drug's long circulation in the bloodstream; conversely, doxorubicin alone did not result in significant delivery to the skin, possibly owing to its short half-life in the blood. This study serves as an important finding for clinical applications of drug targeting [10].Lipoplatin® (Regulon Inc., Mountain View, CA, USA) is a liposomal cisplatin encapsulated within liposomes with an average diameter of 110 nm. Lipoplatin is used to treat cancer in Kaposi's sarcoma and multiple myeloma. Lipoplatin has substantially reduced the renal toxicity, peripheral neuropathy, ototoxicity, myelotoxicity as well as nausea, vomiting and asthenia of cisplatin in Phase I, II and III clinical studies with enhanced or similar efficacy to cisplatin [11]. MyocetTM (Elan Pharmaceuticals Inc., One Research Way, NJ, USA), a non-PEGylated liposomal product (average diameter: 180 nm) encapsulating doxorubicin citrate, has been shown to offer a significant decrease in cardiotoxicity compared with doxorubicin in the treatment of metastatic breast cancer patients [12]. Daunoxome® (NeXstar Pharmaceuticals, Boulder, CO, USA) is an anticancer liposomal product with a particle size range of 60–80 nm and encapsulates daunorubicin. Daunorubicin was recently marketed for the treatment of Kaposi's sarcoma in AIDS [6]. Lipusu® (Luye Pharma Group Co. Ltd, Beijing, China), an anticancer liposomal product that encapsulates paclitaxel and was marketed in China in 2006 for the indications of oophoron and ovarian metastatic carcinoma [13]. Aizhen and colleagues compared the cytotoxic and anticancer effects of Lipusu with those of paclitaxel injection in the same dose, and suggested that Lipusu had similar anticancer activity in vitro and in vivo but its toxicity was lower than that of paclitaxel injection [14]. In another study, Chen and colleagues compared Lipusu with conventional paclitaxel treatments for breast cancer and non-small-cell lung cancer, and demonstrated that both therapies had similar efficacy; however, Lipusu reduced the incidence of serious hypersensitive reactions significantly compared with conventional paclitaxel [15]. Onco TCS™ (Enzon Pharmaceuticals Inc., Bridgewater, NJ, USA) is another liposomal product (diameter range: 120–130 nm) of vincristine that is awaiting approval by the FDA as a single agent for the treatment of patients with relapsed aggressive non-Hodgkin's lymphoma after a combination therapy [8].ConclusionThis article discussed recent developments in the nanopharmacology and toxicology of liposomes regarding their role in emerging nanoliposomal formulations for the treatment of cancer. The marketed liposomal products have already made an impact on cancer treatment owing to their dual function: reduction of the toxicity of existing treatments and maximization of efficacy by selective targeting of tumors. Analytical approaches for liposomes are required that reflect the properties of the liposomes and the release kinetics of the encapsulated drug in tissues, in addition to plasma pharmacokinetics. Furthermore, novel drug delivery systems (e.g., stimulus responsive functions) are required to exploit the liposomal products, enabling advanced chemotherapy with higher efficacy and lower toxicity.AcknowledgementsMadaswamy S Muthu acknowledges the Department of Science and Technology (DST), New Delhi, India, for the award of the BOYSCAST Fellowship (SR/BY/L-41/09) for young scientists in the year of 2009–2010.Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.Papers of special note have been highlighted as: ▪ of interestBibliography1 Feng SS: Nanoparticles of biodegradable polymers for new concepts chemotherapy. Expert Rev. Med. Devices1,115–125 (2004).▪ Describes various comprehensive concepts on the biodegradable nanoparticles for chemotherapy.Crossref, Medline, CAS, Google Scholar2 Muthu MS, Rajesh CV, Mishra A, Singh S: Stimulus responsive targeted nanomicelles for effective cancer therapy. Nanomedicine (Lond.)4,657–667 (2009).Link, CAS, Google Scholar3 Huang C: Studies on phosphatidylcholine vesicles, formation and physical characteristics. Biochemistry8,344–352 (1969).Crossref, Medline, CAS, Google Scholar4 Lasic DD, Papahadjopoulos D: Medical Application of Liposomes. Elsevier, Amsterdam, The Netherlands (1998).Google Scholar5 Helfrich W: The size of bilayer vesicles generated by sonication. Phys. Lett. A50,115–116 (1974).Crossref, Google Scholar6 Bawarski WE, Chidlowsky E, Bharali DJ, Mousa SA: Emerging nanopharmaceuticals. Nanomedicine4,273–282 (2008).Crossref, Medline, CAS, Google Scholar7 Feng SS, Ruan G, Li QT: Fabrication and characterizations of a novel drug delivery device liposomes-in-microsphere (LIM). Biomaterials25,5181–5189 (2004).Crossref, Medline, CAS, Google Scholar8 Muthu MS, Singh S: Targeted nanomedicines: effective treatment modalities for cancer, AIDS and brain disorders. Nanomedicine (Lond.)4,105–118 (2009).Link, CAS, Google Scholar9 Ogawara K, Un K, Tanaka K et al.: In vivo anti-tumor effect of PEG liposomal doxorubicin (DOX) in DOX-resistant tumor-bearing mice: involvement of cytotoxic effect on vascular endothelial cells. J. Control. Release133,4–10 (2009).Crossref, Medline, CAS, Google Scholar10 Yokoyama M: Drug targeting with nano-sized carrier systems. J. Artif. Organs8,77–84 (2005).Crossref, Medline, CAS, Google Scholar11 Boulikas T: Clinical overview on Lipoplatin: a successful liposomal formulation of cisplatin. Expert Opin. Investig. Drugs18,1197–1218 (2009).Crossref, Medline, CAS, Google Scholar12 Batist G, Barton J, Chaikin P et al.: Myocet (liposome-encapsulated doxorubicin citrate): a new approach in breast cancer therapy. Expert Opin. Pharmcother.3,1739–1751 (2002).Crossref, Medline, CAS, Google Scholar13 Zhang Q, Huang XE, Gao LL: A clinical study on the premedication of paclitaxel liposome in the treatment of solid tumors. Biomed. Pharmacother.63,603–607 (2009).Crossref, Medline, CAS, Google Scholar14 Yang A, Li J, Xu H, Chen H: A study on antitumor effect of liposome encapsulated paclitaxel in vivo and in vitro.Bull. Chin. Cancer15,862–864 (2006).CAS, Google Scholar15 Chen Q, Zhang Q, Liu J et al.: Multi-center prospective randomized trial on paclitaxel liposome and traditional taxol in the treatment of breast cancer and non-small-cell lung cancer. Chin. J. Oncol.25,190–192 (2003).Google Scholar101 Data Standards Manual (monographs): Dosage Form LinkGoogle Scholar102 Liposome drug products www.fda.gov/ohrms/dockets/ac/01/slides/3763s2_08_martin/sld001.htmGoogle ScholarFiguresReferencesRelatedDetailsCited ByTPGS Decorated Liposomes as Multifunctional Nano-Delivery Systems14 November 2022 | Pharmaceutical Research, Vol. 40, No. 1Nanoprobes for advanced nanotheranostic applicationsDevelopmental neurotoxicity of silver nanoparticles: the current state of knowledge and future directions3 August 2022 | Nanotoxicology, Vol. 59High antibacterial activity of new eco‐friendly and biocompatible polyurethane nanocomposites based on Fe 3 O 4 /Ag and starch moieties16 February 2022 | Polymer Engineering & Science, Vol. 62, No. 5Preferential uptake of glucose-functionalized liposomes by cancer cellsB12-functionalized PEGylated liposomes for the oral delivery of insulin: In vitro and in vivo studiesJournal of Drug Delivery Science and Technology, Vol. 69Development of Supramolecules in the Field of Nanomedicines16 January 2023Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations5 July 2021 | Journal of Nanobiotechnology, Vol. 19, No. 1Stimuli-responsive nanoliposomes as prospective nanocarriers for targeted drug deliveryJournal of Drug Delivery Science and Technology, Vol. 66A conjugated polymer‐liposome complex: A contiguous water‐stable, electronic, and optical interface21 November 2020 | View, Vol. 2, No. 1Glucose-Functionalized Liposomes for Reducing False Positives in Cancer Diagnosis24 December 2020 | ACS Nano, Vol. 15, No. 1Drug Delivery Using Theranostics: An Overview of its Use, Advantages and Safety AssessmentCurrent Nanoscience, Vol. 16, No. 1Polymer Composites for Structural, Device, and Biomedical Applications26 March 2019Pharmacological Study of Hybrid NanostructuresPhotoresponsive Micelle-Incorporated Doxorubicin for Chemo-Photodynamic Therapy to Achieve Synergistic Antitumor Effects4 June 2018 | Biomacromolecules, Vol. 19, No. 8Practical aspects in size and morphology characterization of drug-loaded nano-liposomesInternational Journal of Pharmaceutics, Vol. 547, No. 1-2Properties of POPC/POPE supported lipid bilayers modified with hydrophobic quantum dots on polyelectrolyte cushionsColloids and Surfaces B: Biointerfaces, Vol. 158Antimicrobial properties and dental pulp stem cell cytotoxicity using carboxymethyl cellulose-silver nanoparticles deposited on titanium plates29 March 2016 | Acta Biomaterialia Odontologica Scandinavica, Vol. 2, No. 1Preparation and characterisation of silver nanoparticle coated on cellulose paper: evaluation of their potential as antibacterial water filter22 July 2016 | Journal of Experimental Nanoscience, Vol. 11, No. 17Development of a large peptoid–DOTA combinatorial library23 September 2016 | Peptide Science, Vol. 106, No. 5The Influential Factors on Antibacterial Behaviour of Copper and Silver Nanoparticles24 March 2015 | Indian Chemical Engineer, Vol. 58, No. 3Nanoparticle-based combination drug delivery systems for synergistic cancer treatment19 May 2016 | Journal of Pharmaceutical Investigation, Vol. 46, No. 4Transferrin receptor-targeted vitamin E TPGS micelles for brain cancer therapy: preparation, characterization and brain distribution in rats2 October 2015 | Drug Delivery, Vol. 23, No. 5Transition from passive to active targeting of oral insulin nanomedicines: enhancement in bioavailability and glycemic control in diabetesDhansukh Kaklotar, Poornima Agrawal, Allabakshi Abdulla, Rahul P Singh, Sonali , Abhishesh K Mehata, Sanjay Singh, Brahmeshwar Mishra, Bajarangprasad L Pandey, Anshuman Trigunayat & Madaswamy S Muthu12 May 2016 | Nanomedicine, Vol. 11, No. 11Reality Check for Nanomaterial-Mediated Therapy with 3D Biomimetic Culture Systems18 April 2016 | Advanced Functional Materials, Vol. 26, No. 23Photoinactivation and Toxicity of Nano-sized TiO2 on Paint Microflora Using Visible Lights17 December 2015 | JOM, Vol. 68, No. 4Comparative Study on Characteristics and Cytotoxicity of Bifunctional Magnetic-Silver Nanostructures: Synthesized Using Three Different Reducing Agents16 March 2016 | Acta Metallurgica Sinica (English Letters), Vol. 29, No. 4Solubilized delivery of paliperidone palmitate by d- alpha-tocopheryl polyethylene glycol 1000 succinate micelles for improved short-term psychotic management22 May 2014 | Drug Delivery, Vol. 23, No. 1Formulation and physiologic factors affecting the pharmacology of carrier-mediated anticancer agents14 July 2015 | Expert Opinion on Drug Metabolism & Toxicology, Vol. 11, No. 9Liposome as efficient system for intracellular delivery of bioactive molecules24 April 2015Plasma Treatment in Textile Industry25 August 2014 | Plasma Processes and Polymers, Vol. 12, No. 2Preparation and characterization of Fe-Tetranitro phthalocyanine/polyurethane blends2 August 2014 | Journal of Applied Polymer Science, Vol. 132, No. 3Polymeric multifunctional nanomaterials for theranostics1 January 2015 | Journal of Materials Chemistry B, Vol. 3, No. 34Trends of Gold Nanoparticle-based Drug Delivery System in Cancer TherapyJournal of Experimental & Clinical Medicine, Vol. 6, No. 6Waterborne Polyurethane Adhesives Based on Gelatine-Stabilized AgNPs with Improved Antimicrobial Properties20 May 2014 | The Journal of Adhesion, Vol. 90, No. 10Novel Waterborne Polyurethane Adhesives Based on Ag@SiO 2 Nanocomposites10 March 2014 | The Journal of Adhesion, Vol. 90, No. 5-6Potentials and emerging trends in nanopharmacologyCurrent Opinion in Pharmacology, Vol. 15Broad-spectrum bioactivities of silver nanoparticles: the emerging trends and future prospects10 January 2014 | Applied Microbiology and Biotechnology, Vol. 98, No. 5Effects of Polymeric Stabilizers on the Synthesis of Gold NanoparticlesJournal of Materials Science & Technology, Vol. 30, No. 2Production and Physicochemical Characteristics of Silver-Containing Polyurethane Systems5 March 2014 | Theoretical and Experimental Chemistry, Vol. 49, No. 6Size-controlled silver nanoparticles synthesized over the range 5–100 nm using the same protocol and their antibacterial efficacy1 January 2014 | RSC Adv., Vol. 4, No. 8Plasma-polymerized HMDSO coatings to adjust the silver ion release properties of Ag/polymer nanocomposites24 October 2013 | Journal of Nanoparticle Research, Vol. 15, No. 11Trastuzumab-conjugated vitamin E TPGS liposomes for sustained and targeted delivery of docetaxel4 March 2013 | Expert Opinion on Drug Delivery, Vol. 10, No. 6Copolymers of poly(lactic acid) and d -α-tocopheryl polyethylene glycol 1000 succinate-based nanomedicines: versatile multifunctional platforms for cancer diagnosis and therapy14 January 2013 | Expert Opinion on Drug Delivery, Vol. 10, No. 4Effect of Particle Size on Silver Nanoparticle Deposition onto Dielectric Barrier Discharge (DBD) Plasma Functionalized Polyamide Fabric18 February 2013 | Plasma Processes and Polymers, Vol. 10, No. 3Theranostic liposomes for cancer diagnosis and treatment: current development and pre-clinical success15 October 2012 | Expert Opinion on Drug Delivery, Vol. 10, No. 2In vitro cytotoxicity of silver nanoparticles on osteoblasts and osteoclasts at antibacterial concentrations21 October 2011 | Nanotoxicology, Vol. 7, No. 1Amphiphilic silver-delaminated clay nanohybrids and their composites with polyurethane: physico-chemical and biological evaluationsJournal of Materials Chemistry B, Vol. 1, No. 16Focus on the development of computer-aided nanomedicine designMadaswamy S Muthu13 November 2012 | Nanomedicine, Vol. 7, No. 10Tuning of the ion release properties of silver nanoparticles buried under a hydrophobic polymer barrier12 June 2012 | Journal of Nanoparticle Research, Vol. 14, No. 7Poly(lactide-co-glycolide)/silver nanoparticles: Synthesis, characterization, antimicrobial activity, cytotoxicity assessment and ROS-inducing potentialPolymer, Vol. 53, No. 14Study of quercetin-loaded liposomes as potential drug carriers: in vitro evaluation of human complement activation19 October 2011 | Journal of Liposome Research, Vol. 22, No. 2Emerging patents for cancer-targeted nanomedicinesPharmaceutical Patent Analyst, Vol. 1, No. 2Theranostic liposomes of TPGS coating for targeted co-delivery of docetaxel and quantum dotsBiomaterials, Vol. 33, No. 12In situ synthesis of nano silver/lecithin on wool: Enhancing nanoparticles diffusionColloids and Surfaces B: Biointerfaces, Vol. 92Development of docetaxel-loaded vitamin E TPGS micelles: formulation optimization, effects on brain cancer cells and biodistribution in ratsMadaswamy S Muthu, Sneha Avinash Kulkarni, Yutao Liu & Si-Shen Feng2 March 2012 | Nanomedicine, Vol. 7, No. 3Challenges posed by the scale-up of nanomedicinesMadaswamy S Muthu & Barnabas Wilson2 March 2012 | Nanomedicine, Vol. 7, No. 3The cellular responses and antibacterial activities of silver nanoparticles stabilized by different polymers17 January 2012 | Nanotechnology, Vol. 23, No. 6Resorcinarene bis-crown silver complexes and their application as antibacterial Langmuir–Blodgett filmsOrganic & Biomolecular Chemistry, Vol. 10, No. 10Vitamin E TPGS coated liposomes enhanced cellular uptake and cytotoxicity of docetaxel in brain cancer cellsInternational Journal of Pharmaceutics, Vol. 421, No. 2Antimicrobial polyethyleneimine-silver nanoparticles in a stable colloidal dispersionColloids and Surfaces B: Biointerfaces, Vol. 88, No. 1Doxorubicin variants for hematological malignanciesGiuseppe Visani & Alessandro Isidori21 June 2011 | Nanomedicine, Vol. 6, No. 2 Vol. 5, No. 7 Follow us on social media for the latest updates Metrics History Published online 27 September 2010 Published in print September 2010 Information© Future Medicine LtdKeywordsefficacyliposomesmarketed formulationssafetyAcknowledgementsMadaswamy S Muthu acknowledges the Department of Science and Technology (DST), New Delhi, India, for the award of the BOYSCAST Fellowship (SR/BY/L-41/09) for young scientists in the year of 2009–2010.Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download