Abstract
Liposomes are versatile drug carriers which can be used to solve problems of drug solubility, instability and rapid degradation. Both hydrophilic and hydrophobic drugs can be associated with liposomes and special techniques have been developed for the efficient loading of weak acids and weak bases into liposomes.
Liposomes can function as sustained release systems for drugs and the rate of release can be manipulated. Advantage can be taken of the substantial changes in pharmacokinetics which often accompanies the association of drugs with liposomes. New formulations of liposomes, sterically stabilised with substances like surface-grafted polyethylene glycol have circulating half-lives in humans of up to 2 days. These long circulation times allow concentration of liposomal drug in regions of increased vascular permeability like solid tumours an decreased delivery of drug to normal tissues. Alterations of the biodistribution of drugs, when they are liposomes-associated, in general leads to significant overall decreases in drug toxicity but can also increase toxicity in some tissues. The use of targeting ligands to increase the selectivity of delivery of liposomal drugs to target tissues is currently under development. An understanding of how liposome association can alter drug properties can lead to their rational development in the treatment of many diseases.
Similar content being viewed by others
References
Allen TM. Liposomal drug delivery. Curr Opin Colloid Interface Sci 1996; 1: 645–51
Sharma A, Sharma US. Liposomes in drug delivery: progress and limitations. Int J Pharm 1997; 154: 123–40
Casper ES, Schwartz GK, Sugarman A, et al. Phase I trial of dose-intense liposome-encapsulated doxorubicin in patients with advanced sarcoma. J Clin Oncol 1997; 15(5): 2111–7
Muggia F, Hainsworth JD, Jeffers S, et al. Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol 1997; 15: 987–93
Ranson M, Howell A, Cheeseman S, et al. Liposomal drug delivery. Cancer Treat Rev 1996; 22: 365–79
Woodle MC, Storm G, editors. Long-circulating Liposomes: old drugs, new therapeutics. Georgetown (TX): Landes Bioscience, 1998
Wasan KM, Lopez-Berenstein G. The past, present and future uses of liposomes in treating infectious diseases. Immuno-pharmacol Immunotoxicol 1995; 17: 1–15
Abraham E, Park YC, Covington P, et al. Liposomal prostaglandin E(1) in acute respiratory distress syndrome: a placebo-controlled, randomized, double-blind, multicenter clinical trial. Crit Care Med 1996; 24(1): 10–5
Deol P, Khuller GK. Lung specific stealth liposomes: stability, biodistribution and toxicity of liposomal antitubercular drugs in mice. Biochim Biophys Acta 1997; 1334: 161–72
Dipali SR, Lin Y-J, Ravis WR, et al. Pharmacokinetics and tissue distribution of long circulating liposomal formulation of 2′,3′ dideoxyinosine. Int J Pharm 1997; 152: 89–97
Defrise-Quertain F, Chatelain P, Delmelle M, et al. Model studies for drug entrapment and liposome stability. In: Gregoriadis G, editor. Liposome technology. Vol. 2. 1st ed. Boca Raton (FL): CRC Press Inc., 1984: 1–17
Allen TM, Mehra T, Hansen CB, et al. Stealth liposomes: an improved sustained release system for 1-β-D-arabino-furanosylcytosine. Cancer Res 1992; 52: 2431–9
Perez-Soler R, Francis K, ai-Baker S, et al. Preparation and characterization of liposomes containing a lipophilic cisplatin derivative for clinical use. J Microencapsul 1994; 11(1): 41–54
Perez-Soler R, Neamati N, Zou Y, et al. Annamycin circumvents resistance mediated by the multidrug resistance-associated protein (MRP) in breast MCF-7 small-cell lung UMCC-1 cancer cell lines selected for resistance to etoposide. Int J Cancer 1997; 71: 35–41
Perez-Soler R, Shin DM, Siddik ZH, et al. Phase I clinical and pharmacological study of liposome-entrapped NPDP administered intrapleurally in patients with malignant pleural effusions. Clin Cancer Res 1997; 3: 373–9
Haran G, Cohen R, Bar LK, et al. Transmembrane ammonium sulfate gradients in liposomes produce efficient and stable entrapment of amphipathic weak bases. Biochim Biophys Acta 1993; 1151: 201–15
Cullis PR, Hope MJ, Bally MB, et al. Influence of pH gradients on the transbilayer transport of drugs, lipids, peptides and metal ions into large unilamellar liposomes. Biochim Biophys Acta 1997; 1331: 187–211
Gabizon A, Catane R, Uziely B, et al. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res 1994; 54: 987–92
Cevc G, editor. Phospholipids handbook. New York (NY): Marcel Dekker Inc., 1993
Sharma A, Straubinger RM. Novel taxol formulations, preparation and characterization of taxol-containing liposomes. Pharm Res 1994; 11: 889–96
Bernard E, Dubois J-L, Wepierre J. Importance of sebaceous glands in cutaneous penetration of an antiandrogen: target effect of liposomes. J Pharm Sci 1997; 86: 573–8
Reddi E. Role of delivery vehicle for photosensitizers in the photodynamic therapy of tumours. J Photochem Photobiol 1997; 37: 189–95
Borsa J, Whitmore GF, Valeriote FA, et al. Studies on the persistence of methotrexate, cytosine arabinoside, and leucovorin in serum of mice. J Natl Cancer Inst 1969; 42(2): 235–42
Burke TG, Gao X. Stabilization of topotecan in low pH liposomes composed of distearoylphosphatidylcholine. J Pharm Sci 1994; 83(7): 967–9
’t Hart BA, Elferink DG, Frijfhout JW, et al. Liposome-mediated peptide loading of MHC-DR molecules in. vivo. FEBS Lett 1997; 409: 91–5
ten Hagen TLM, Eggermont AMM. A rat extremity soft tissue sarcoma model for the study of systemic treatment with Stealth liposome-encapsulated tumor necrosis factor-α and cytotoxic agents. Adv Drug Del Rev 1997; 24: 245–56
Khanna C, Anderson PM, Hasz DE, et al. Interleukin-2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases. Cancer 1997; 79: 1409–21
Allen TM. A study of phospholipid interactions between high-density lipoproteins and small unilamellar vesicles. Biochim Biophys Acta 1981; 640: 385–97
Scherphof GL, Damen J, Wilschut, J. Interactions of liposomes with plasma proteins. In: Gregoriadis G, editor. Liposome technology. Vol. 2.1st ed. Boca Raton (FL): CRC Press, 1984: 205–24
Wasan KM, Morton RE. Differences in lipoprotein concentration and composition modify the plasma distribution of free and liposomal annamycin. Pharm Res 1996; 13: 462–8
Horowitz AT, Barenholz Y, Gabizon AA. In vitro cytotoxicity of liposome-encapsulated doxorubicin: dependence on liposome composition and drug release. Biochim Biophys Acta 1992; 1109: 203–9
Allen TM, Newman MS, Woodle MC, et al. Pharmacokinetics and anti-tumor activity of vincristine encapsulated in sterically stabilized liposomes. Int J Cancer 1995; 62: 199–204
Lim HJ, Masin D, Madden TD, et al. Influence of drug release characteristics on the therapeutic activity of liposomal mitoxantrone. J Pharmacol Exp Ther 1997; 281: 566–73
Chu CJ, Szoka C. pH-sensitive liposomes. J Liposome Res 1991; 4: 361–95
Srinath P, Jain NK. Signal sensitive liposomes. Indian Drugs 1994; 31(7): 284–90
Boman NL, Masin D, Mayer LD, et al. Liposomal vincristine which exhibits increased drug retention and increased circulation longevity cures mice bearing P388 tumors. Cancer Res 1994; 54: 2830–3
Kirpotin D, Hong K, Mullah N, et al. Liposomes with detachable polymer coating: destabilization and fusion of dioleoyl-phosphatidylethanolamine vesicles triggered by cleavage of surface-grafted poly(ethylene glycol). FEBS Lett 1996; 388: 115–8
Wu NZ, Braun RD, Gaber MH, et al. Simultaneous measurement of liposome extravasation and content release in tumors. Microcirculation 1997; 4(1): 83–101
Thierry AR, Vige D, Couglin SS, et al. Modulation of doxorubicin resistance in multidrug resistant cells by liposomes. FASEB J 1993; 7: 572–9
Sharma A, Mayhew E, Straubinger RM. Antitumor effect of taxol-containing liposomes in a taxol-resistant murine tumor model. Cancer Res 1993; 53(24): 5877–81
Suzuki S, Inoue K, Hongoh A, et al. Modulation of doxorubicin resistance in a doxorubicin-resistant human leukaemia cell by an immunoliposome targeting transferrin receptor. Br J Cancer 1997; 76(1): 83–9
Pecheur EI, Hoekstra D, Sainte-Marie J, et al. Membrane anchorage brings about fusogenic properties in a short synthetic peptide. Biochemistry 1997; 36: 3773–81
Hwang KJ. Liposome pharmacokinetics. In: Ostro MJ, editor. Liposomes: from biophysics to therapeutics. New York (NY): Marcel Dekker, 1987: 109–56
Allen TM, Hansen CB, Lopes de Menezes DE. Pharmacokinetics of long circulating liposomes. Adv Drug Del Rev 1995; 16: 267–84
Scherphof GL, Velinova M, Kamps J, et al. Modulation of pharmacokinetic behavior of liposomes. Adv Drug Del Rev 1997; 24: 179–91
Alving CR, Steck EA, Chapman WLJ, et al. Therapy of leishmaniasis: superior efficacies of liposome-encapsulated drugs. Proc Natl Acad Sci U S A 1978; 75(6): 2959–63
Allen TM. The use of glycolipids and hydrophilic polymers in avoiding rapid uptake of liposomes by the mononuclear phagocyte system. Adv Drag Del Rev 1994; 13: 285–309
Torchilin VP, Trubetskoy VS. Use of polyoxyethylene-lipid conjugates as long-circulating carriers for delivery of therapeutic and diagnostic agents. Adv Drag Del Rev 1995; 16: 141–55
Ceh B, Winterhalter M, Frederik PM, et al. Stealth liposomes: from theory to product. Adv Drag Del Rev 1997; 24: 165–77
Mezei M. Liposomes and the skin. In: Gregoriadis G, Florence AT, Patel MH, editors. Liposomes in drag delivery. Yverdon, Switzerland: Harwood Academic, 1993: 125–35
Cevc G. Transfersomes, liposomes and other lipid suspensions on the skin: permeation, enhancement, vesicle penetration, and transdermal drag delivery. Crit Rev Ther Drug Carrier Syst 1996; 13: 257–388
Young AM, Gregoriadis G. Photolysis of retinol in liposomes and its protection with tocopherol and oxybenzone. Photochem Photobiol 1996; 63(3): 344–52
Chen H, Langer R. Magnetically-responsive polymerized liposomes as potential oral delivery vehicles. Pharm Res 1997; 14(4): 537–40
Kakinuma K, Tanaka R, Takahashi H, et al. Targeting chemotherapy for malignant brain tumor using thermosensitive liposome and localized hyperthermia. J Neurosurg 1996; 84(2): 180–4
Siegal T, Horowitz A, Gabizon A. Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model: biodistribution and therapeutic efficacy. J Neurosurgery 1995; 83(6): 1029–37
Khalifa A, Dodds D, Rampling R, et al. Liposomal distribution in malignant glioma: possibilities for therapy. Nucl Med Commun 1997; 18: 17–23
Boman NL, Tron VA, Bally MB, et al. Vincristine-induced dermal toxicity is significantly reduced when the drug is given in liposomes. Cancer Chemother Pharmacol 1996; 37(4): 351–5
Uziely B, Jeffers S, Isacson R, et al. Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies. J Clin Oncol 1995; 13: 1777–85
Northfelt DW, Martin FJ, Working P, et al. Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumour localization, and safety in patients with AIDS-related Kaposi’s sarcoma. J Clin Pharmacol 1996; 36: 55–63
Forssen EA. The design and development of DaunoXomeR for solid tumor targeting in vivo. Adv Drug Del Rev 1997; 24: 133–50
Allen TM. Toxicity of drug carriers to the mononuclear phagocyte system. Adv Drug Del Deliv 1988; 2: 55–67
Parr MJ, Bally MB, Cullis PR. The presence of GM1 in liposomes with entrapped doxorubicin does not prevent RES blockade. Biochim Biophys Acta 1993; 1168: 239–52
Amantea MA, Forrest A, Northfelt DW, et al. Population pharmacokinetics and pharmacodynamics of pegylated-liposomal doxorubicin in patients with AIDS-related Kaposi’s sarcoma. Clin Pharmacol Therap 1997; 61(3): 301–11
Goebel F-D, Goldstein D, Goos M, et al. Efficacy and safety of Stealth® liposomal doxorubicin in AIDS-related Kaposi’s sarcoma. Br J Cancer 1996; 73: 989–94
Wu NZ, Da D, Rudoll TL, et al. Increased microvascular permeability contributes to preferential accumulation of stealth liposomes in tumour tissue. Cancer Res 1993; 53: 3765–70
Bakker-Woudenberg IAJM, Storm G, Woodle MC. Liposomes in the treatment of infections. J Drug Target 1994; 2: 363–71
Unezaki S, Maruyama K, Hosoda J-I, et al. Direct measurement of the extravasation of polyethyleneglycol-coated liposomes into solid tumor tissue by in vivo fluorescence microscopy. Int J Pharm 1996; 144: 11–7
Gabizon A, Goren D, Horowitz AT, et al. Long-circulating liposomes for drug delivery in cancer therapy: a review of biodistribution studies in tumor-bearing animals. Adv Drug Del Rev 1997; 24: 337–44
Bakker-Woudenberg IA, ten Kate MT, Stearne-Cullen LE, et al. Efficacy of gentamicin or ceftazidime entrapped in liposomes with prolonged blood circulation and enhanced localization in Klebsiella pneumoniae-infected lung tissue. J Infect Dis 1995; 171: 938–47
Allen TM, Moase EH. Therapeutic opportunities for targeted liposomal drug delivery. Adv Drag Del Rev 1996; 21: 117–33
MacLean AL, Symonds G, Ward R. Immunoliposomes as targeted delivery vehicles for cancer therapeutics. Int J Oncol 1997; 11: 325–32
Lopes de Menezes DE, Pilarski LM, Allen TM. In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-cell lymphoma. Cancer Res 1998; 58: 3320–30
Kersten GFA, Crommelin DJA. Liposomes and ISCOMS as vaccine formulations. Biochim Biophys Acta 1995; 124(12): 117–38
Huang L, Li S. Liposomal gene delivery: a complex package. Nature Biotech 1997; 15: 620–1
Mahato RI, Takakura Y, Hasida M. Nonviral vectors for in vivo gene delivery: physicochemical and pharmacokinetic considerations. Crit Rev Ther Drag CarrierSyst 1997; 14(2): 133–72
Feigner PL. Nonviral strategies for gene therapy. Sci Am 1997 June; 102–10
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Allen, T.M. Liposomal Drug Formulations. Drugs 56, 747–756 (1998). https://doi.org/10.2165/00003495-199856050-00001
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199856050-00001