Liposomes as Drug Delivery System: An Updated Review
The liposomes were the first Nano medicine to be accepted for clinical use. They are the spherical vesicles that possess mid empty aqueous space, which is encircled by a phospholipids bilayer. Liposomes have immense capability to prevent the degradation of drugs, reduce side effects and are thus increasingly used for targeted drug delivery. The drugs can either be incorporated inside the aqueous space (hydrophilic drugs) or inside the phospholipids bilayer (hydrophobic drugs) of liposomes for the targeted drug delivery. Considering the importance of liposomes as a drug delivery system, the present review paper tries to look into its details. The entire paper is classified into six parts. The first part is introductory. The second part discusses the classification of liposomes. In the third segment, the structural components of liposomes are detailed. The fourth portion of the paper talks about methods of preparation of liposomes. In the fifth segment, the characterization of liposomes is discussed. The sixth part discusses the application of liposomes and the last part is given to concluding observation. Literature shows distinct types of liposomes, categorized based on size, number of lipid layers, composition and preparation method. They are recently used for various nanoscale drugs formulation and a piece of concrete evidence was seen recently in recommended drug for black fungus i.e., Liposomal Amphotericin B. Although, their development and application are remaining the challenge due to costly and tedious processes involved in their production and development. Therefore, further research and development are required to perform to overcomes these challenges.
Keywords: Liposome, characterization, amphiphatic, controlled release, phospholipids
2. Lasic D, Papahadjopoulos D. Liposomes revisited. Science. 1995; 267(5202). https://doi.org/10.1126/science.7871422
3. Vyas SP, Khar RK. Targeted And Controlled Drug Delivery: Novel Carrier Systems. 2006:421-427.
4. Samad A, Sultana Y, Aqil M. Liposomal Drug Delivery Systems:An Updated Review. Current Drug Delivery. 2007; 4:297-305. https://doi.org/10.2174/156720107782151269
5. Riaz M. Liposomes preparation methods. Pakistan journal of pharmaceutical sciences. 1996:65-77.
6. Gregoriadis G, Florence AT. Liposomes in Drug Delivery. Drugs. 1993:15-28. https://doi.org/10.2165/00003495-199345010-00003
7. Dunnick JK, Rooke JD, Aragon S, Kriss JP. Alteration of Mammalian Cells by Interaction with Artificial Lipid Vesicles. Cancer Research. 1976(36):2385-2389.
8. Fujisawa T, Miyai H, Hironaka K, et al. Liposomal diclofenac eye drop formulations targeting the retina: formulation stability improvement using surface modification of liposomes. Int J Pharm. 2012; 436:564-567. https://doi.org/10.1016/j.ijpharm.2012.07.024
9. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965; 13:238-252. https://doi.org/10.1016/S0022-2836(65)80093-6
10. McIntosh TJ. The effect of cholesterol on the structure of phosphatidylcholine bilayers. Biochim Biophys Acta. 1978; 513:43-58. https://doi.org/10.1016/0005-2736(78)90110-4
11. Cullis PR. Lateral diffusion rates of phosphatidylcholine in vesicle membranes, effects of cholesterol and hydrocarbon phase transitions. FEBS Letters. 1976; 70:223-228. https://doi.org/10.1016/0014-5793(76)80762-4
12. Li X, Chen D, Le C, et al. Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake. Int J Nanomedicine. 2011(6):3151--3162. https://doi.org/10.2147/IJN.S25741
13. Specialized Drug Delivery System,Manufacturing and Production Technology. In: Tyle P, ed. Pharmaceutical manufacturing of liposomes: Marcell Dekker; 1990.
14. Sharma A, Sharma US. Liposomes in drug delivery: Progress and limitations. International Journal of Pharmaceutics. 1997; 154(2):123-140. https://doi.org/10.1016/S0378-5173(97)00135-X
15. Gregoriadis G. Engineering liposomes for drug delivery,progress and problems. Trends in Biotechnology. 1995; 13(12):527-537. https://doi.org/10.1016/S0167-7799(00)89017-4
16. Deshmukh R, Gawale S, Bhagwat M, Ahire P, Derle N. A Review on: liposomes. World journal of pharmacy and pharmaceutical sciences, (03):506-517.
17. Gaurav R, Tejal S. Liposomal drug delivery syst em: an overview. IJPBA. 2011; 2(6):1575-1580.
18. Dua J, Rana PA, Bhandari DK. Liposome: methods of preparation and applications. IJPSR. 2012; 3(2):14-20.
19. Hwang T, Lee WR, Hua SC, Fang JY. Cisplatin encapsulated in phosphatidylethanolamine liposomes enhances the in vitro cytotoxicity and in vivo intratumor drug accumulation against melanomas. J Dermatol Sci. 2007; 46:11-20. https://doi.org/10.1016/j.jdermsci.2006.12.011
20. Prabhu P, Kumar N, Dhondge G, et al. Preparation and evaluation of liposomes of brimonidine tartrate as an ocular drug delivery system. International Journal of Research in Pharmaceutical Sciences. 2010; 1(4):502-508. https://doi.org/10.4103/0975-1483.71623
21. Lopes L, Scarpa M, Pereira N, Oliveira LCd, Oliveira A. Interaction of sodium diclofenac with freeze-dried soya phosphatidylcholine and unilamellar liposomes. Braz J Pharm Sci. 2006; 42(4):497-504. https://doi.org/10.1590/S1516-93322006000400004
22. Sipai A, Vandana Y, Y M, V.V P. Liposomes: an overview. JPSI. 2012; 1(1):13-21.
23. Jadhav MP, Nagarsenker MS, Gaikwad RV, Samad A, Kshirsagar NA. Formulation and Evaluation of Long Circulating Liposomal Amphotericin B: A Scinti-kinetic Study using 99mTc in BALB/C Mice. Indian J Pharm Sci. 2011; 73(1): 57-64. https://doi.org/10.4103/0250-474X.89757
24. Chauhan T, Arora S, Parashar B, Chandel. Liposome Drug Delivery. IJPCS. 2012; 1(3):1103-1113.
25. Nidhal K, Athmar D. Preparation and evaluation of salbutamol liposomal suspension using chloroform film method. Mustansiriya Medical Journal. 2012; 11(2):39-44.
26. Anwekar H, Patel S, Singhai AK. Liposome- as drug carriers. Int J of Pharm & Life Sci. 2011; 2(7): 945-951.
27. Traïkia M, Warschawski DE, Recouvreur M, Cartaud J, Devaux PF. Formation of unilamellar vesicles by repetitive freeze-thaw cycles: characterization by electron microscopy and 31P-nuclear magnetic resonance. Eur Biophys J. 2000; 29(3):184-195. https://doi.org/10.1007/s002490000077
28. Kumar A, Badde S, Kamble R, Pokharkar V. Development and characterization of liposomal drug delivery system for nimesulide. Int J Pharm Pharm Sci. 2010; 2(4):87-89.
29. Da Costa C, Moraes A. Encapsulation of 5-fluorouracil. Maringá. 2003; 25(1):53-61.
30. Niu M, Lu Y, Hovgaard L, Wu W. Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation. Int J Nanomedicine. 2011; 6:1115-1166.
31. Mirzaee M, Owlia P, Mehrabi M. Comparison of the bact ericidal activity of amikacin in free and liposomal formulation against gram-negative and gram-positive bacteria. Jundishapur Journal of Natural Pharmaceutical Products. 2009; 4(1):1-7.
32. Hathout RM, Mansour S, Mortada ND, Guinedi AS. Liposomes as an ocular delivery system for acetazolamide: In vitro and in vivo studies. AAPS PharmSciTech. 2007; 8(1): E1-E12. https://doi.org/10.1208/pt0801001
33. John DF, AA U, Chigbo UJ, Paul US, Ikenna E. TOLNAFTATE LOADED LIPOSOMES- DESIGN, AND IN-VITRO EVALUATION. Universal Journal of Pharmaceutical Research. 2016; 1(2):48-53. https://doi.org/10.22270/ujpr.v1i2.R6
34. Winden E. Freeze-drying of liposomes: theory and practice. Methods Enzymol. 2003; 367:99-110. https://doi.org/10.1016/S0076-6879(03)67008-4
35. Lo Yl, Tsai JC, Kuai J. Liposomes and disaccharides as carriers in spray-dried powder formulations of superoxide dismutase. J Control Release. 2004; 94:259-272. https://doi.org/10.1016/j.jconrel.2003.09.019
36. Alving C. Liposomes as carriers of antigens and adjuvants. J. Immunol. Methods. 1991; 140: 1-13. https://doi.org/10.1016/0022-1759(91)90120-5
37. Vemuri S, Yu T, Yu CD, Degroot JS, Roosdorp N. In Vitro Interaction of Sized and Unsized Liposome Vesicles with High Density Lipo Proteins. Drug Development and Industrial Pharmacy. 1990; 16(9):1579-1584. https://doi.org/10.3109/03639049009074385
38. Ellens H, Mayhew E, Rustum YM. Reversible depression of the reticulo-endothelial system by liposomes. Biochim Biophys Acta. 1982; 714:479-485. https://doi.org/10.1016/0304-4165(82)90157-X
39. Guiot P, Baudhuin P, Gotfredsen C. Morphological characterization of liposome suspensions by stereological analysis of freeze fracture replicas from spray-frozen samples. J Microsc. 1980; 120:159-174. https://doi.org/10.1111/j.1365-2818.1980.tb04132.x
40. Koshkina NV, Golunski E, Roberts LE, Gilbert BE, Knight V. Cyclosporin A aerosol improves the anticancer effect of paclitaxel aerosol in mice. J. Aerosol Med. 2004; 17:7-14. https://doi.org/10.1089/089426804322994415
41. Kersten GFA, Crommelin DJA. Liposomes and ISCOMS as vaccine formulations. Biochim biophys acta. 1995; 1241:117-138. https://doi.org/10.1016/0304-4157(95)00002-9
42. Remington. The Science and Practice of Pharmacy. Vol 1. 21 ed: B.I Publishers Pvt Ltd.
43. Shargel L, Pong SW, Yu ABC. Applied Biopharmaceutics and Pharmacokinetics. Vol 5.
44. The relations existing between chemical constitution, distribution and pharmacological action. Collected Studies on Immunity. Vol 2: Wiley; 1906.
45. Sawant R, Torchilin V. Challenges in development of targeted liposomal therapeutics. AAPSJ. 2012; 14(2):303-315. https://doi.org/10.1208/s12248-012-9330-0
46. Torchilin VP. Liposomes as targetable drug carriers. Crit Rev Ther Drug Carrier Syst. 1985; 2(1):65-115.
47. Grit M, Zuidam NJ, Crommelin DJA. Liposome Technology. Boca Raton: CRC Press; 1993.
48. Taira MC, Chiaramoni NS, Pecuch KM, Alonso Romanowski S. Stability of liposomal formulations in physiological conditions for oral drug delivery. Drug Deliv. 2004; 11:123-128. https://doi.org/10.1080/10717540490280769
49. Uster PS, Deamer DW. Fusion competence of phosphatidylserine-containing liposomes quantitatively measured by a fluorescence resonance energy transfer assay. Arch. Biochem. Biophys. 1981; 209(2):385-395. https://doi.org/10.1016/0003-9861(81)90296-4
50. Mayer LD, Cullis PR, Balley MB. Medical Application Of Liposome. Elsevier Science BV. 1998.
51. Dunnick JK, Rooke JD, Aragon S, Kriss JP. Alteration of Mammalian Cells by Interaction with Artificia lLipid Vesicles. Cancer Research. 1976; 36:2385-2389.
52. Blume G, Cevc G. Liposomes for the sustained drug release in vivo. Biochim. Biophys. Acta. 1990; 1029:91-97. https://doi.org/10.1016/0005-2736(90)90440-Y
53. Abra R, Bosworth M, Hunt C. Liposome disposition in vivo, effects of pre-dosing with liposomes. Res. Commun. Chem. Pathol. Pharmacol. 1980; 29:349-360.
54. Allison AG, Gregoriadis G. Liposomes as immunological adjuvants. Nature. 1974; 252(5480). https://doi.org/10.1038/252252a0
55. Watson DS, Endsley AN, Huang L. Design considerations for liposomal vaccines, influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens. Vaccine. 2012; 30:2256-2272. https://doi.org/10.1016/j.vaccine.2012.01.070
56. Mc Cauley JA, Flory's B, Mc Comb TG. Biochim. Biophys. Acta. 1992; 30(112).
57. Schroeder U, Sommerfeld P, Ulrich S, Sabel BA. Nanoparticle technology for delivery of drugs across the blood-brain barrier. Journal of pharmaceutical sciences. 1998; 87(11):1305-1307. https://doi.org/10.1021/js980084y
58. Alving CR, Steck EA, Chapman Jr WL, et al. Therapy of leishmaniasis: superior efficacies of liposome-encapsulated drugs. Proc Natl Acad Sci U S A. 1978; 75(6):2959-2963. https://doi.org/10.1073/pnas.75.6.2959
59. Alving C, Steck E, Chapman W, Waits V, Hendricks L. Therapy of leishmaniasis, superior efficacies of liposome encapsulated drugs. Proc. Natl. Acad. Sci. 1978; 75:2959-2963. https://doi.org/10.1073/pnas.75.6.2959
60. Desiderio JV, Campbel SG. J. Infect. Dis. 1983;148: 563-570. https://doi.org/10.1093/infdis/148.3.563
61. Gabizon A. Selective tumor localization and improved therapeutic index of anthracyclines encapsulated in long-circulating liposomes. Cancer Research. 1992; 52(4):891-896.
62. Lawrence M, Jennifer RM, Marcel B. J. Pharm. Sci. 1998; 88(1):96.
63. Torchilin VP. Recent approaches to intracellular delivery of drugs and DNA and organelle targeting. Annu Rev Biomed Eng. 2006; 8:343-375. https://doi.org/10.1146/annurev.bioeng.8.061505.095735
64. Chen X, Huang W, Wong B, et al. Liposomes prolong the therapeutic effect of anti-asthmatic medication via pulmonary delivery. Int J Nanomedicine. 2012; 7:1139-1148. https://doi.org/10.2147/IJN.S28011
65. Hua S, Wu SY. The use of lipid-based nanocarriers for targeted pain therapies. Front. Pharmacol. 2013; 4:143. https://doi.org/10.3389/fphar.2013.00143
66. Monteiro N, Martins A, Reis RL, Neves NM. Liposomes in tissue engineering and regenerative medicine. J R Soc Interface. 2014; 11. https://doi.org/10.1098/rsif.2014.0459
67. Torchilin VP. Immunoliposomes and PEGylated immunoliposomes: possible use for targeted delivery of imaging agents. Immunomethods. 1994; 4:244-258. https://doi.org/10.1006/immu.1994.1027
68. Willis M, Forssen E. Ligand-targeted liposomes. Adv. Drug Deliv. Rev. 1998; 29:249-271. https://doi.org/10.1016/S0169-409X(97)00083-5
69. Hua S, Marks E, Schneider JJ, Keely S. Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue. Nanomedicine. 2015; 11:1117-1132. https://doi.org/10.1016/j.nano.2015.02.018
70. Puri A, Loomis K, Smith B, et al. Lipid-based nanoparticles as pharmaceutical drug carriers: from concepts to clinic. Crit. Rev. Ther. Drug Carrier Syst. 2009; 26:523-580. https://doi.org/10.1615/CritRevTherDrugCarrierSyst.v26.i6.10
71. Riehemann K, Schneider SW, Luger TA, Godin B, Ferrari M, Fuchs H. Nanomedicine-challenge and perspectives. Angew. Chem. Int. Ed Engl. 2009; 48:872-897. https://doi.org/10.1002/anie.200802585
72. Sawant RR, Torchilin VP. Challenges in development of targeted liposomal therapeutics. AAPSJ. 2012; 14:303-315. https://doi.org/10.1208/s12248-012-9330-0
73. Kraft JC, Freeling JP, Wang Z, Ho RJ. Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems. J. Pharm. Sci. 2014; 103:29-52. https://doi.org/10.1002/jps.23773
74. Zhang H, Wang G, Yang H. Drug delivery systems for differential release in combination therapy. Expert Opin. Drug Deliv. 2011; 8: 171-190. https://doi.org/10.1517/17425247.2011.547470
75. Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv. Drug Deliv. Rev. 2013; 65:36-48. https://doi.org/10.1016/j.addr.2012.09.037
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