Recent Patents, Formulation Techniques, Classification and Characterization of Liposomes

Author(s): Reena Sheoran, Sukhbir Lal Khokra, Viney Chawla, Harish Dureja*.

Journal Name: Recent Patents on Nanotechnology

Volume 13 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: During past decades, liposomes have emerged as efficient carriers for drugs, diagnostics, vaccines, nutrients and other bioactive agents. Liposomes, the spherical vesicles consisting of phospholipids bilayer have the ability to encapsulate both lipophilic and hydrophilic drugs. Extensive studies have been done in the past for investigating a number of drugs and genes for controlled release with liposomal formulation. Liposomes have also been investigated for their use in cancer treatment. Liposomes offer various advantages because of their biocompatible, biodegradable, nontoxic and non-immunogenic nature.

Methods: Liposomes have cell-specific targeting with important applications in the fields of nanotechnology like cancer therapy, diagnosis, gene delivery, cosmetics, agriculture and in food technology. They are prepared by various methods like sonication method, ethanol injection method, lipid film hydration method, micro-emulsion method.

Conclusion: This review will provide an overview of classification, the various formulation methods, characterization, patented formulations and applications of liposomes with future prospects.

Keywords: Liposomes, phospholipids, formulation, characterization, encapsulation, biocompatible.

Ota A, Istenic K, Skrt M, et al. Encapsulation of pantothenic acid into liposomes and into alginate or alginate-pectin microparticles loaded with liposomes. J Food Eng 2018; 229: 21-31.
Spuch C, Navarro C. Liposomes for targeted delivery of active agents against neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease). J Drug Deliv 2011; 469679: 1-12.
Bagul R, Mahajan V, Dhake A. New Approaches in nanoparticulate drug delivery system - A review. Int J Curr Pharm Res 2012; 4(3): 29-38.
Sahoo SK, Labhasetwar V. Nanotech approaches to drug delivery and imaging. Drug Discov Today 2003; 8(24): 1112-20.
Anwekar H, Patel S, Singhai AK. Liposome- as drug carriers. Int J Pharm Life Sci 2011; 2(7): 945-51.
Shahi S, Sonwane U, Zadbuke N, Tadwee I. Design and development of diphenhydramine hydrochloride topical liposomal drug delivery system. Int J Pharm Pharm Sci 2013; 5(3): 534-42.
Johnston MJW, Semple SC, Klimuk SK, Ansell S, Maurer N, Cullis PR. Characterization of the drug retention and pharmacokinetic properties of liposomal nanoparticles containing dihydrosphingomyelin. Biochim Biophys Acta 2007; 1768: 1121-7.
Hofheinz RD, Vogt SUG, Beyer U, Hochhaus A. Liposomal encapsulated anti-cancer drugs. Anticancer Drugs 2005; 16: 691-07.
Akbarzadeh A, Sadabady RR, Davaran S, et al. Liposome: Classification, preparation, and applications. Nanoscale Res Lett 2013; 8: 102-11.
Maherani B, Arab Tehrany E, Mozafari MR, Gaiani C, Linder M. Liposomes: A review of manufacturing techniques and targeting strategies. Curr Nanosci 2011; 7: 436-52.
Chang HI, Yeh MK. Clinical development of liposome-based drugs: Formulation, characterization, and therapeutic efficacy. Int J Nanomedicine 2012; 7: 49-60.
Scherphof G, Roerdink F, Waite M, Parks J. Disintegration of phosphatidylcholine liposomes in plasma as a result of interaction with high-density lipoproteins. Biochim Biophys Acta 1978; 542: 296-307.
Allen TM, Cleland LG. Serum-induced leakage of liposome contents. Biochim Biophys Acta 1980; 597: 418-26.
Senior J, Gregoriadis G. Is half-life of circulating liposomes determined by changes in their permeability? FEBS Lett 1982; 145: 109-14.
Boman NL, Bally MB, Cullis PR, Mayer LD, Webb MS. Encapsulation of vincristine in liposomes reduces toxicity and improves its anti-tumor efficacy. J Liposome Res 1995; 5(3): 523-41.
Cullis PR. Lateral diffusion rates of phosphatidylcholine in vesicle membranes: Effects of cholesterol and hydrocarbon phase transitions. FEBS Lett 1976; 70: 223-8.
McIntosh TJ. The effect of cholesterol on the structure of phosphatidylcholine bilayers. Biochim Biophys Acta 1978; 513: 43-58.
Storm G, Roerdink FH, Steerenberg PA, Jong WH, Crommelin DJ. Influence of lipid composition on the antitumor activity exerted by doxorubicin-containing liposomes in a rat solid tumor model. Cancer Res 1987; 47: 3366-72.
Cullis PR, Hope MJ. The bilayer stabilizing role of sphingomyelin in the presence of cholesterol: A 31P NMR study. Biochim Biophys Acta 1980; 597: 533-42.
Allen TM. A study of phospholipid interactions between high-density lipoproteins and small unilamellar vesicles. Biochim Biophys Acta 1981; 640: 385-97.
Campbell RB, Ying B, Kuesters GM, Hemphill R. Fighting cancer: From the bench to bedside using second generation cationic liposomal therapeutics. J Pharm Sci 2009; 98(2): 411-29.
Davis T, Farag SS. Treating relapsed or refractory Philadelphia chromosome-negative acute lymphoblastic leukemia: Liposome-encapsulated vincristine. Int J Nanomedicine 2013; 8: 3479-88.
Krishna R, Webb MS, St Onge G, Mayer LD. Liposomal and nonliposomal drug pharmacokinetics after administration of liposome-encapsulated vincristine and their contribution to drug tissue distribution properties. J Pharmacol Exp Ther 2001; 298(3): 1206-12.
Ellens ME, Rustum YM. Reversible depression of the reticuloendothelial system by liposomes. Biochim Biophys Acta 1982; 714: 479-85.
Hsu MJ, Juliano RL. Interactions of liposomes with the reticuloendothelial system. Nonspecific and receptor-mediated uptake of liposomes by mouse peritoneal macrophages. Biochim Biophys Acta 1982; 720: 411-9.
Allen TM, Murray L, MacKeigan S, Shah M. Chronic liposome administration in mice: Effects on reticuloendothelial function and tissue distribution. J Pharmacol Exp Ther 1984; 229: 267-75.
Abra RM, Bosworth ME, Hunt CA. Liposome disposition in vivo: Effects of pre-dosing with liposomes. Res Commun Chem Pathol Pharmacol 1980; 29: 349-60.
Kao YJ, Juliano RL. Interactions of liposomes with the reticuloendothelial system. Effects of reticuloendothelial blockade on the clearance of large unilamellar vesicles. Biochim Biophys Acta 1981; 677: 453-61.
Proffitt RT, Williams LE, Presant CA, et al. Liposomal blockade of the reticuloendothelial system: Improved tumor imaging with small unilamellar vesicles. Science 1983; 220: 502-5.
Hwang KJ, Padki MM, Chow DD, Essien HE, Lai JY, Beaumier PL. Uptake of small liposomes by non-reticuloendothelial tissues. Biochim Biophys Acta 1987; 901: 88-96.
Hoekstra D, Scherphof G. Effect of fetal calf serum and serum protein fractions on the uptake of liposomal phosphatidylcholine by rat hepatocytes in primary monolayer culture. Biochim Biophys Acta 1979; 551: 109-21.
Moghimi SM, Patel HM. Differential properties of organ-specific serum opsonins for liver and spleen macrophages. Biochim Biophys Acta 1989; 984: 379-83.
Chonn A, Semple SC, Cullis PR. Association of blood proteins with large unilamellar liposomes in vivo. Relation to circulation lifetimes. J Biol Chem 1992; 267: 18759-65.
Allen TM. Stealth liposomes: Avoiding reticuloendothelial uptake.In: Lopez-Berestein G, Fidler I. Eds.Liposomes in the therapy of infectious disease and cancer UCLA symposium in molecular and cellular biology. New York: CRC Press 1989; pp. 405-15.
Klibanov AL, Maruyama K, Torchilin VP, Huang L. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett 1990; 268: 235-7.
Blume G, Cevc G. Liposomes for the sustained drug release in vivo. Biochim Biophys Acta 1990; 1029: 91-7.
Allen TM, Hansen CB, Martin F, Redemann C, Yau-Young A. Liposomes containing synthetic lipid derivatives of polyethylene glycol show prolonged circulation half-lives in vivo. Biochim Biophys Acta 1991; 1066: 29-36.
Maruyama K, Yuda T, Okamoto A, Ishikura C, Kojima S, Iwatsuru M. Effect of molecular weight in amphipathic polyethyleneglycol on prolonging the circulation time of large unilamellar liposomes. Chem Pharm Bull 1991; 39: 1620-2.
Senior J, Delgado C, Fisher D, Tilcock C, Gregoriadis G. Influence of surface hydrophilicity of liposomes on their interaction with plasma protein and clearance from the circulation: Studies with the polyethylene glycol coated vesicles. Biochim Biophys Acta 1991; 1062: 77-82.
Papahadjopoulos D, Allen TM, Gabizon A, et al. Sterically stabilized liposomes: Improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci USA 1991; 88: 11460-4.
Allen TM, Hansen CB. Pharmacokinetics of stealth vs. conventional liposomes: Effect of dose. Biochim Biophys Acta 1991; 1068: 133-41.
Sebastian AB, Ravoo BJ. Dynamic reactions of liposomes. Soft Matter 2014; 10: 69-74.
Torchilin PV. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 2005; 4: 145-60.
Rohilla S, Chauhan C, Singh R, et al. Liposomes: Preparations and Applications. Int J Drug Dev Res 2012; 4(4): 108-15.
Gregoriadis G, Florence AT. Liposomes in drug delivery: Clinical, diagnostic and ophthalmic potential. Drugs 1993; 45: 15-28.
Goyal P, Goyal K, Kumar VSG, Singh A, Katare OP, Mishra DN. Liposomal drug delivery systems-clinical applications. Acta Pharm 2005; 55: 1-25.
Lasic DD. Applications of liposomes. In: Lipowsky R, Sackmann E. eds.Handbook of biological physics. Amsterdam: Elsevier 1995; pp. 491-519.
Kaur L, Kaur P, Khan MU. Liposome as a drug carrier - A review. Int J Res Pharm Chem 2013; 3(1): 121-8.
Mansoori MA, Agrawal S, Jawade S, Khan MI. A review on liposome. Int J Adv Res Pharm Bio Sci 2012; 2(4): 453-64.
Kant S, Kumar S, Prashar B. A complete review on liposomes. Int Res J Pharm 2012; 3(7): 10-6.
Marripati S, Umasankar K, Reddy PJ. A Review on Liposomes. Int J Res Pharm Nano Sci 2014; 3(3): 159-69.
Dua JS, Rana AC, Bhandari AK. Liposome: Methods of preparation and applications. Int J Clin Pharmacol Res 2012; 3(2): 14-20.
Deepthi V, Kavitha AN. Liposomal drug delivery system-a review. RGUHS J Pharm Sci 2014; 4(2): 47-56.
Samad A, Sultana Y, Aqil M. Liposomal drug delivery systems: An update review. Curr Drug Deliv 2007; 4(4): 297-05.
Priyanka RK, Yadav JD, Kumar AV. Liposomes: A novel drug delivery system. Int J Curr Pharm Res 2011; 3(2): 10-8.
Popovska O, Simonovska J, Kavrakovski Z, Rafajlovska V. An Overview: Methods for preparation and characterization of liposomes as drug delivery systems. Int J Pharm Phytopharm Res 2013; 3(3): 182-9.
LiQ K. Chang S, Wang Z, Zhao X, Chen D. A novel micro-emulsion and micelle assembling method to prepare DEC205 monoclonal antibody coupled cationic nanoliposomes for simulating exosomes to target dendritic cells. Int J Pharm 2015; 491(2): 105-12.
Mohammad R. Liposome’s preparation methods. Pak J Pharm Sci 1996; 19(1): 65-77.
Kataria S, Sandhu P, Bilandi A, Akansha M, Kapoor B. Stealth liposomes. Int J Res Ayurveda Pharm 2011; 2(5): 1534-8.
Hamilton RLJ, Goerke J, Luke SSG, Williams MC, Havel RJ. Unilamellar liposomes made with the French pressure cell: A simple preparative and semiquantitative technique. J Lipid Res 1980; 21(8): 981-92.
Maheswaran A, Brindha P, Mullaicharam AR, Masilamani K. Liposomal drug delivery systems - A review. Int J Pharm Sci Rev Res 2013; 23(1): 295-01.
Sipai Altaf Bhai M, Yadav V, Mamatha Y, Prasanth VV. Liposomes: An overview. J Pharm Sci Innov 2012; 1(1): 13-21.
Deamer D, Bangham AD. Large volume liposomes by an ether vaporization method. Biochim Biophys Acta 1976; 443: 629-34.
Batzri S, Korn ED. Single bilayer liposomes prepared without sonication. Biochim Biophys Acta 1973; 298: 1015-9.
Szoka FJ, Papahadjopoulos D. Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci USA 1978; 75(9): 4194-8.
Cronstein BN, Corciulo C. Methods of compositions for treating osteoarthritis and promoting cartilage formation. US Patent 20180036238, 2018.
Nicastro A, Barbarini AL. Method for preparing a liposomal rehydration salt formulation. US Patent 20180028561, 2018.
Yang J, Stephen HW, Herman CJ. Combinational liposome composition for cancer therapy. US Patent 20180015039, 2018.
Bayever E, Dhindsa N, Fitzgerald JB, Laivins P, Moyo V, Niyikiza C, Kim J-Y. Methods for treating pancreatic cancer using combination therapies comprising liposomal Irinotecan. US Patent 20170368056-A1, 2017.
Renu Gupta. Methods for treating pulmonary disorders with liposomal Amikacin formulations. US Patent 20170360818, 2017
Niyikiza C, Moyo V, Xu Z, Khalifa K. Targeted liposomal Gemcitabine compositions and methods thereof. US Patent 20170319482, 2017.
Kliche KO, Mescheder A, Piccart M. Treatment of triple receptor negative breast cancer. US Patent 20170273934, 2017
Ting- Bin Y, Shi Z, Su SH, Howden T. stable liposomal formulations of carbonic anhydrase inhibitors for ocular drug delivery. US Patent 20170042809, 2017.
Leor J, Tamar BM, Radka HG, et al. Targeted liposomes encapsulating iron complexes and their uses. US Patent 20170273906, 2017
Venkatraman S, Boey YCF, Nataranjan JV. Sustained timolol maleate delivery from liposomes for glaucoma therapy and ocular hypertension. US Patent 20170246175, 2017
Reynolds JG, Olivier KJ, Hendriks BS, Wickham T, Klinz S, Geretti E. Dosage and administration for preventing cardiotoxicity in treatment with ERBB-2 targeted immunoliposomes comprising anthracycline chemotherapeutic agents. US Patent 20170189335 2017
Jaafari MR, Zahmatkeshan M, Sorkhabadi SMR. Cancer targeting by anti-egfr peptides and applications thereof. US Patent 20170183380, 2017.
Bayever E, Fitzgerald JB, Kim J, Klinz S. Treatment of breast cancer with liposomal Irinotecan. US Patent 20170151226, 2017.
Gabizon A, Ohana P, Wang A. Combination therapy comprising a liposomal prodrug of Mitomycin C and Radiotherapy. US Patent 20170119895, 2017
Yu TB, Shi Z, Su SH, Howden T. Stable liposomal formulations of alpha 2 adrenergic agonists for ocular delivery. US Patent 20170119666, 2017
Boni LT, Miller BS. Sustained release of anti-infectives. US Patent 20170100420, 2017.
Gonda I, Blanchard J, Cippola DC, Bermudez LEM. Liposomal ciprofloxacin formulations with activity against non-tuberculous mycobacteria. US Patent 20170071934, 2017
Joseph Jongeul Jeung. Vitamin C delivery system and liposomal composition thereof. US Patent 20160367480, 2016.
McGhee W, Blackle J, Grapperhaus M, Rochon L, Deverakonda K. Modified docetaxel liposomes formulations and uses thereof. US Patent 20160250177, 2016.
Amoabediny G, Ochi MM, Rezayat SM, Akbarzadeh A, Ebrahimi B. Targeted nano-liposome co-entrapping anti-cancer drugs. US Patent 20160228362, 2016.
Sharma S, Mishra L, Grover I, Gupta A, Kaur K. Liposomes: Vesicular system an overview. Int J Pharm Pharm Sci 2010; 2(4): 11-7.
Pandey H, Rani R, Agarwal V. Liposome and their applications in cancer therapy. Braz Arch Biol Technol 2016; 59: 1-10.
Cagdas M, Sezer AD, Bucak S. Liposomes as potential drug carrier systems for drug delivery.. In: Ali Demir Sezer eds.Application of nanotechnology in drug delivery. London: IntechOpen 2014; pp. 1-50.
Li W, Szoka Jr F.C.. Lipid-based nanoparticles for nucleic acid delivery. Pharm Res 2007; 24(3): 438-49.
Theresa MA, Cullis PR. Liposomal drug delivery systems: From concept to clinical applications. Adv Drug Deliv Rev 2013; 65: 36-48.
Garg T, Goyal AK. Liposomes: Targeted and controlled delivery system. Drug Deliv Lett 2014; 4: 62-71.
Wanga B, Zinselmeyera BH, Runnels HA, et al. In vivo imaging implicates CCR2+ monocytes as regulators of neutrophil recruitment during arthritis. Cell Immunol 2012; 278: 103-12.
Fujiwara SN, Hirayama F, Ogata Y, Ikeda H, Ikebuchi K. Phagocytosis in vitro of polyethylene glycol-modified liposome encapsulated hemoglobin by human peripheral blood monocytes plus macrophages through scavenger receptors. Life Sci 2001; 70(3): 291-300.
Raj S, Jose S, Sumod US, Sabitha M. Nanotechnology in cosmetics: Opportunities and challenges. J Pharm Bioallied Sci 2012; 4(3): 186-93.
Garg T, Goyal AK. Iontophoresis: Drug delivery system by applying an electrical potential across the skin. Drug Deliv Lett 2012; 2(4): 270-80.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [17 - 27]
Pages: 11
DOI: 10.2174/1872210513666181127110413
Price: $58

Article Metrics

PDF: 44