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. 2007 May 1;6(4):465–474. doi: 10.1111/j.1582-4934.2002.tb00450.x

Designing of ‘intelligent’ liposomes for efficient delivery of drugs

Manuela Voinea 1, Maya Simionescu 1,✉
PMCID: PMC6741336  PMID: 12611636

Abstract

The liposome‐ vesicles made by a double phospholipidic layers which may encapsulate aqueous solutions‐ have been introduced as drug delivery vehicles due to their structural flexibility in size, composition and bilayer fluidity as well as their ability to incorporate a large variety of both hydrophilic and hydrophobic compounds. With time the liposome formulations have been perfected so as to serve certain purposes and this lead to the design of “intelligent” liposomes which can stand specifically induced modifications of the bilayers or can be surfaced with different ligands that guide them to the specific target sites. We present here a brief overview of the current strategies in the design of liposomes as drug delivery carriers and the medical applications of liposomes in humans.

Keywords: liposomes, drug delivery, gene delivery, targeted delivery, human therapy

References

  • 1. Woodle M.C., Newman L., Collins L., Redermann C., Martin F., Improved long circulating (Stealth) liposomes using synthetic lipids, Proc. Int. Symp. Contr. Rel. Bioact. Mat., 17: 77–78, 1990. [Google Scholar]
  • 2. Kaneda Y., Uchida T., Ishiura M., Okada Y., The improved efficient method for introducing macromolecules into cells using HVJ (Sendai virus) liposomes with gangliosides, Exp. Cell. Res., 173: 56–69, 1987. [DOI] [PubMed] [Google Scholar]
  • 3. Mannino R.J., Gould‐Fogerite S., Liposome‐mediated gene transfer, Biotechniques, 6: 682–690, 1988. [PubMed] [Google Scholar]
  • 4. Yatvin M.B., Kreutz W., Horwitz B.A., Shinizky M., pH‐sensitive liposomes, Possible clinical implications, Science, 210: 1253–1254, 1980. [DOI] [PubMed] [Google Scholar]
  • 5. Slepushkin V.A., Simoes S., Dazin P., Newman M.S., Guo L. S., Pedroso de Lima M.C., Duzgunes N., Sterically stabilized pH‐sensitive liposomes, J Biol Chem, 272: 2382–2388, 1997. [DOI] [PubMed] [Google Scholar]
  • 6. Li S., Huang L., Targeted delivery of antisense oligodeoxynucleotides formulated in a novel lipidic vector, J Liposome Res 8, 239–250, 1998. [Google Scholar]
  • 7. Felgner P.L., Gadek T., Holm M., Roman R., Chan H., Wenz M., Northrop J., Ringold G.M., Danielsen R.M., Lipofection, A highly efficient, lipid‐mediated DNA transfection procedure, Proc Natl Acad Sci, 84: 7413–7417, 1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Farhood H, Serbina N, Huang L, The role of DOPE in cationic liposomes mediated gene transfer, Biochim Biophys Acta, 1235: 289–295, 1995. [DOI] [PubMed] [Google Scholar]
  • 9. Meyer O., Kirpotin D., Hong K., Sternberg B., Park JW., Woodle MC, Papahadjopoulos D., Cationic liposomes coated with polyethylene glycol as carriers for oligonucleotides, J Biol Chem, 273: 15621–15627, 1998. [DOI] [PubMed] [Google Scholar]
  • 10. Ho RJY, Rouse BT, Huang L, Target‐sensitive immunoliposomes, Preparation and characterization, Biochemistry, 25: 5500–5506, 1986. [DOI] [PubMed] [Google Scholar]
  • 11. Bloemen PGM, Henricks PAJ, van Blois L., van den Tweel M.C., Bloem A. C., Nijkamp, Crommelin DJA., Storm G., Adhesion molecules: a new target for immunoliposome‐mediated drug delivery, FEBS Lett, 357: 140–144, 1995. [DOI] [PubMed] [Google Scholar]
  • 12. Bendas G., Krause A., Schmidt R., Vogel J., Rothe U., Selectins as new targets for immunoliposome‐mediated drug delivery, A potential way of anti‐inflammatory therapy, Pharm Acta Helv, 73: 19–26, 1998. [DOI] [PubMed] [Google Scholar]
  • 13. Kirby C, Gregoriadis G., The effect of lipid composition of small unilamellar liposomes containing melphalan and vincristine on drug clearance after injection in mice, Biochem Pharmacol, 32: 609–615, 1983. [DOI] [PubMed] [Google Scholar]
  • 14. Torchilin VP, Shtilman MI, Trubetskoy VS, Whiteman K, Milstein AM., Amphiphilic vinyl polymers effectively prolong liposome circulation time in vivo, Biochim Biophys Acta, 1195: 181–184, 1994. [DOI] [PubMed] [Google Scholar]
  • 15. Namba Y, Sakakibara T, Masada M, Ito F, Oku N., Glucoronate modified liposomes with prolonged circulation time, Chem Pharm Bull, 38: 1663–1666, 1990. [DOI] [PubMed] [Google Scholar]
  • 16. Forssen EA, Coulter DM, Proffitt RT., Selective in vivo localization of daunorubicin small unilamellar vesicles in solid tumors, Cancer Res, 52: 3255–3261, 1992. [PubMed] [Google Scholar]
  • 17. Rosilio V., Baszkin A, Polysaccharide‐coated liposomes in Puisieux F, Couvreur P, Delattre J, Devissaguet J‐P, eds., Liposomes: New methods and new trends in their applications, Editions de Sante, France , Paris , 1995, pp 43–71. [Google Scholar]
  • 18. Gabizon PA, Papahadjopoulos D, Liposome formulations with prolonged circulation time in blood and enhanced uptake in tumors, Proc.Natl.Acad.Sci.USA, 85: 6949, 1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Liu D, Song YK, Liu F, Antibody dependent, complement mediated liver uptake of liposomes containing GM1, Pharm Res, 12: 1775–1780, 1995. [DOI] [PubMed] [Google Scholar]
  • 20. Lasic DD, Martin FJ, Gabizon A, Huang SK, Papahadjopoulos D, Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times, Biochim Biophys Acta, 1070: 187–192, 1991. [DOI] [PubMed] [Google Scholar]
  • 21. Lee RJ, Low PS., Folate‐mediated tumor cell targeting of liposome‐entrapped doxorubicin in vitro, Biochim Biophys Acta, 1233: 134–44, 1995. [DOI] [PubMed] [Google Scholar]
  • 22. Vidal M., Sainte‐MArie J., Philippot J.R., Bienvenue A., The influence of coupling transferrin to liposomes or minibeads on its uptake and fate in leukemic L2C cells, FEBS Lett, 216: 159–163, 1987. [DOI] [PubMed] [Google Scholar]
  • 23. Kamps J.A.A.M., Morselt H.W.M., Swart P.J., Meijer D.K.F., Scherphof G.L., Massive targeting of liposomes, surface‐modified with anionized albumins, to hepatic endothelial cells, Proc Natl Acad Sci, 94: 11681–11685, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Cansell M., Parisel C., Jozefonvicz J., Letourneur D., Liposomes coated with chemically modified dextran interact with human endothelial cells, Inc. J Biomed Mater Res., 44: 140–148, 1999. [DOI] [PubMed] [Google Scholar]
  • 25. Bogdanov A.A., Klibanov A.L., Torchilin V.P., Protein imobilization on the surface of liposomes via carbodimiide actination in the presece of N‐hydroxysulfosuccimide‐FEBS Lett, 231: 381–384, 1988. [DOI] [PubMed] [Google Scholar]
  • 26. Allen T.M., Agrawal A.K., Ahmad I., Hansen C.B., Zalipsky S., Antibody‐mediated targeting of long‐circulating(StealthR) liposomes, J Liposome Res 4, 1–25, 1994. [Google Scholar]
  • 27. Hansen C.B., Kao G.Y., Moase E. H., Zalipsky S., Allen T.M., Attachment of antibodies to sterically stabilized liposomes: evaluation, comparison and optimization of coupling procedures, Biochim Biophys Acta, 1239: 133–144, 1995. [DOI] [PubMed] [Google Scholar]
  • 28. Crommelin D.J.A., Daemen T., Scherphof G.L., Vingerhoeds M.H., Heeremans J.L.M. Kluft C., Storm G., Liposomes: vehicles for the target and controlled delivery of peptides and proteines, J Control Release, 46: 165–175, 1997. [Google Scholar]
  • 29. Bendas G., Krause A., Bakowsky U., Vogel J., Rothe U., Targetability of novel immunoliposomes prepared by a new antibody conjugation technique, Int J Pharm, 181: 79–93, 1999. [DOI] [PubMed] [Google Scholar]
  • 30. Lopes de Menezes DE, Pilarski LM, Allen TM., In vitro and in vivo targeting of immunoliposomal doxorubicin to human B‐cell lymphoma, Cancer Res., 58: 3320–3330, 1998. [PubMed] [Google Scholar]
  • 31. Mori A, Kennel SI, Waalkes MVB, Scherphof GL, Huang L, Characterization of organ‐specific immunoliposomes for delivery of 3′, 5′‐O‐dipalmitoyl‐5‐fluoro‐2′‐deoxyuridine in a mouse lung‐metastasis model, Cancer Chemother Pharmacol, 35: 447–56, 1995. [DOI] [PubMed] [Google Scholar]
  • 32. Park JW, Hong K, Carter P, Asgari H, Guo LY, Keller GA, Wirth C, Shalaby R, Kotts, Wood WI, Papahadjouploulos D, Benz CC, Development of anti‐p185HER2 immunoliposomes for cancer therapy, Proc Natl Acad Sci, 92: 1327–1331, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. Park JW, Hong K, Kirpotin DB, Meyer O, Papahadjopoulos D, Benz CC., Anti‐HER2 immunoliposomes for targeted therapy of human tumors, Cancer Lett., 118: 153–60, 1997. [DOI] [PubMed] [Google Scholar]
  • 34. Murray JL, Monoclonal antibody treatment of solid tumors. A coming of age, Sem Oncol., 27: 64–70, 2000. [PubMed] [Google Scholar]
  • 35. Shi G, Guo W, Stephenson SM, Lee RJ., Efficient intracellular drug gene delivery using folate receptor‐targeted pH‐sensitive liposomes composed of cationic/anionic lipid combinations, J Control Release, 80: 309–319, 2002. [DOI] [PubMed] [Google Scholar]
  • 36. Mizoue T, Horibe T, Maruyama K, Takizawa T, Iwatsuru M, Kono K, Yanagie H, Moriyasu F., Targetability and intracellular delivery of anti‐BCG antibody‐modified, pH‐sensitive fusogenic immunoliposomes to tumor cells, Int J Pharm., 237: 129–37, 2002. [DOI] [PubMed] [Google Scholar]
  • 37. 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., 60: 1197–1201, 2000. [PubMed] [Google Scholar]
  • 38. Ho RJY, Rouse BT, Huang L, Target‐sensitive immunoliposomes as an efficient drug carrier for antivitral activity, J Biol Chem, 262: 13973–13978, 1987. [PubMed] [Google Scholar]
  • 39. Yuan F, Leunig M, Huang SK, Berk DA, Papahadjopoulos D, Jain RK., Microvascular permeability and interstitial penetration of sterically stabilized (stealth)liposomes in a human tumor xenograft, Cancer Res, 54: 3352–3356, 1994. [PubMed] [Google Scholar]
  • 40. Lasic DD, Novel applications of liposomes, TIBTECH, 16: 307–321, 1998. [DOI] [PubMed] [Google Scholar]
  • 41. Ahmad I, Longenecker M, Samuel J, Allen TM, Antibody‐targeted delivery of doxorubicin entrapped in sterically stabilized liposomes can eradicate lung‐cancer in mice, Cancer Res, 53: 1484–1488, 1993. [PubMed] [Google Scholar]
  • 42. Huwyler J, Yang J, Pardridge WM., Receptor mediated delivery of daunomycin using immunoliposomes: Pharmacokinetics and tissue distribution in the rat, J Pharmacol. Exp. Therap., 282: 1541–1546, 1997. [PubMed] [Google Scholar]
  • 43. VanBree C, Krooshoop JJ, Rietbroek RC, Kipp JBA, Bakker PJM., Hyperthermia enhances tumor uptake and antitumor efficacy of thermostable liposomal daunorubicin in a rat solid tumor, Cancer Res., 56: 563–568, 1996. [PubMed] [Google Scholar]
  • 44. Maruyama K, Unezaki S, Takahashi N, Iwatsuru M., Enhanced delivery of doxorubicin to tumor by longcirculating thermosensitive liposomes and local hyperthermia, Biochim. Biophys. Acta, 1149: 209–16, 1993. [DOI] [PubMed] [Google Scholar]
  • 45. Goren D, Horowitz AT, Zalipsky S, Woodle MC, Yarden Y, Gabizon A., Targeting of stealth liposomes to erbB‐2 (Her/2) receptor: In vitro and in vivo studies, Br J Cancer, 74: 1749–1756, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. Vingerhoeds MH, Steerenberg PA, Hendriks J, Dekker LC, VanHoesel Q, Crommelin DJA, et al. Immunoliposome‐mediated targeting of doxorubicin to human ovarian carcinoma in vitro and in vivo, Br J Cancer 74: 1023–9, 1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47. Forssen E, Willis M., Ligand‐targeted liposomes, Adv Drug Del Rev, 29: 249–71, 1998. [DOI] [PubMed] [Google Scholar]
  • 48. Doi K, Oku N, Toyota T, Shuto S, Sakai A, Itoh H, et al. Therapeutic effect of reticuloendothelial system(RES)‐avoiding liposomes containing a phospholipid analog of 5‐fluorouracil, dipalmitoyl phosphatidyl fluorouridine, in Meth‐A sarcoma‐bearing mice, Biol Pharm Bull, 17: 1414–1416, 1994. [DOI] [PubMed] [Google Scholar]
  • 49. Mayer LD, Nayer R, Thies RL, Bowman NL, Cullis PR, Bally MB., Identification of vesicle properties that enhance the antitumour activity of liposomal vincristine against murine L1210 leukemia, Cancer Chemother Pharmacol, 33: 17–24, 1993. [DOI] [PubMed] [Google Scholar]
  • 50. Mayer LD, Masin D, Nayar R, Boman NL, Bally MB., Pharmacology of liposomal vincristine in mice bearing L1210 ascitic and B16/F10 solid tumors, Br J Cancer, 71: 482–488, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51. Tokudome Y, Oku N, Doi K, Namba Y, Okada S., Antitumour activity of vincristine encapsulated in glucoronide modified long circulating liposomes in mice bearing Meth A sarcoma, Biochim Biophys Acta, 1279: 70–74, 1996. [DOI] [PubMed] [Google Scholar]
  • 52. Oku N, Saito N, Namba Y, Tsukada H, Dolphin D, Okada S., Application of long‐circulating liposomes to cancer photodynamic therapy, Biol Pharm Bull, 20: 670–673, 1997. [DOI] [PubMed] [Google Scholar]
  • 53. Fichtner I, Arndt D, Reska R, Gens J., Pharmacokinetic behaviour of [57CO]bleomycin liposomes in mice: comparison with the unencapsulated substance, Anticancer Drugs, 2: 555–563, 1991. [DOI] [PubMed] [Google Scholar]
  • 54. Lim HJ, Masin D, Madden TD, Bally MB., Influence of drug release characteristics on the therapeutic activity of liposomal mitoxantrone, J Pharmacol Exper Therap, 281: 566–573, 1997. [PubMed] [Google Scholar]
  • 55. Sharma A, Mayhew E, Straubinger RM., Antitumour effect of taxol containing liposomes in a taxol resistant murine tumour model, Cancer Res, 53: 5877–5881, 1993. [PubMed] [Google Scholar]
  • 56. Daoud SS., Combination chemotherapy of human ovarian xenografts with intraperitoneal liposome ‐ incorporated valinomycin and cis ‐ diammine dichloroplatinum (II), Cancer Chemother Pharmacol, 33: 307–312, 1994. [DOI] [PubMed] [Google Scholar]
  • 57. Chamberlain MC, Glantz MJ, Jaeckle KA., A phase 3 trial of intra‐CSF sustained‐release encapsulated cytarabine (Depocyt) versus cytarabine (ara‐C) in the treatment of lymphomatous meningitis (LM), Neurology 52: A245, 1999. [Google Scholar]
  • 58. Deol P, Khuller GK, Joshi K., Therapeutic efficacies of isoniazid and rifampin encapsulated in lung‐specific stealth liposomes against Mycobacterium tuberculosis infection induced in mice, Antimicrob Agent Chemother, 41: 1211–1214, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59. Deol P, Khuller GK, Lung specific stealth liposomes: stability, biodistribution and toxicity of liposomal antitubercular drugs, Biochim Biophys Acta, 1334: 161–172, 1997. [DOI] [PubMed] [Google Scholar]
  • 60. Hockertz S, Franke G, Paulini I, Lohmann‐Matthes ML, Immunotherapy of murine visceral leishmaniasis with murine recombinant IFNγ and MTPPE encapsulated in liposomes, J Interferon Res, 11: 177–185, 1991. [DOI] [PubMed] [Google Scholar]
  • 61. Gregoriadis G, 1995, Engineering liposomes for drug delivery: progress and problems, Trends Biotechnol. 13: 527–537, 1995. [DOI] [PubMed] [Google Scholar]
  • 62. Gregoriadis G, Gursel I, Gursel M, McCormack B., Liposomes as immunological adjuvants and vaccine carriers, J Control Rel, 41: 49–56, 1996. [Google Scholar]
  • 63. Gregoriadis G, Saffie R, Da Souza JB., Liposome mediated DNA vaccination, FEBS Lett, 402: 107–110, 1997. [DOI] [PubMed] [Google Scholar]
  • 64. Gregoriadis G, McCormark B, Obrenovic M, Perrie Y, Yang J‐C, Genetic Vaccines: A role for liposomes in Targeting of Drugs, Eds Gregoriadis G and McCormark B, NATO Science Series, Series A: Life Sciences, 2000, pp: 92–101.
  • 65. Cohen S, Bernstein H, Hewes C, Chow M, Langer R., The pharmacokinetics of, and humoral responses to, antigen delivered by microencapsulated liposomes, Proc Natl Acad Sci USA, 88: 10440–10444, 1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66. Ambrosch F, Wiedermann G, Jonas S, Althaus B, Finkel B, Gluck R, Herzog C., Immunogenicity and protectivity of a new liposomal hepatitis A vaccine, Vaccine, 15: 1209–1213, 1997. [DOI] [PubMed] [Google Scholar]
  • 67. Villaret D, Glisson B, Kenady D, Hanna E, Carey M, Gleich L, Yoo GH, Futran N, Hung MC, Anklesaria P, Heald AE., A multicenter phase II study of tgDCC‐E1A for the intratumoral treatment of patients with recurrent head and neck squamous cell carcinoma, Head Neck, 24: 661–669, 2002. [DOI] [PubMed] [Google Scholar]
  • 68. Hortobagyi GN, Ueno NT, Xia W, Zhang S, Wolf JK, Putnam JB, Weiden PL, Willey JS, Carey M, Branham DL, Payne JY, Tucker SD, Bartholomeusz C, Kilbourn RG, De Jager RL, Sneige N, Katz RL, Anklesaria P, Ibrahim NK, Murray JL, Theriault RL, Valero V, Gershenson DM, Bevers MW, Huang L, Lopez‐Berestein G, Hung MC, Cationic liposome‐mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial, J Clin Oncol, 19: 3422–3433, 2001. [DOI] [PubMed] [Google Scholar]
  • 69. Gill DR, Southern KW, Mofford KA, Seddon T, Huang L, Sorgi F, Thomson A, MacVinish LJ, Ratcliff R, Bilton D, Lane DJ, Littlewood JM, Webb AK, Middleton PG, Colledge WH, Cuthbert AW, Evans MJ, Higgins CF, Hyde SC., A placebocontrolled study of liposome‐mediated gene transfer to the nasal epithelium of patients with cystic fibrosis, Gene Ther, 4: 199–209, 1997. [DOI] [PubMed] [Google Scholar]
  • 70. Alton EW, Stern M, Farley R, Jaffe A, Chadwick SL, Phillips J, Davies J, Smith SN, Browning J, Davies MG, Hodson ME, Durham SR, Li D, Jeffery PK, Scallan M, Balfour R, Eastman SJ, Cheng SH, Smith AE, Meeker D, Geddes DM., Cationic lipid‐mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double‐blind placebo‐controlled trial, Lancet, 353: 947–54, 1999. [DOI] [PubMed] [Google Scholar]
  • 71. Hyde SC, Southern KW, Gileadi U, Fitzjohn EM, Mofford KA, Waddell BE, Gooi HC, Goddard CA, Hannavy K, Smyth SE, Egan JJ, Sorgi FL, Huang L, Cuthbert AW, Evans MJ, Colledge WH, Higgins CF, Webb AK, Gill DR., Repeat administration of DNA/liposomes to the nasal epithelium of patients with cystic fibrosis, Gene Ther, 7: 1156–1165, 2000. [DOI] [PubMed] [Google Scholar]

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