Clinical development of liposome-based drugs: Formulation, characterization, and therapeutic efficacy

International Journal of Nanomedicine

Volumn 7, Issue , 2012, Pages 49-60

  Chang, Hsin I ^a   Yeh, Ming Kung ^b  

^a NATIONAL CHIAYI UNIVERSITY   (Taiwan)

^b NATIONAL DEFENSE MEDICAL CENTER   (Taiwan)

Author keywords

Cationic liposomes; PEGlated liposomes; Temperature sensitive liposomes; Therapeutic effciency; Virosomes

Indexed keywords

1,2 DIOLEOYL 3 TRIMETHYLAMMONIOPROPANE; AMPHOTERICIN B CHOLESTEROL SULFATE; AMPHOTERICIN B LIPID COMPLEX; BLEOMYCIN; CARDIOLIPIN; CHOLESTEROL; CREMOPHOR; CYCLOPHOSPHAMIDE; CYTARABINE; DAUNORUBICIN; DIOLEOYLPHOSPHATIDYLCHOLINE; DIPALMITOYLPHOSPHATIDYLCHOLINE; DISTEAROYLPHOSPHATIDYLCHOLINE; DISTEAROYLPHOSPHATIDYLETHANOLAMINE; DOXORUBICIN; ENDOTAG 1; GEMCITABINE; HEPATITIS A VACCINE; INFLUENZA VACCINE; LEP ETU; LIPO DOX; LIPOSOME; MACROGOL 2000; MONOSTEAROYLPHOSPHATIDYLCHOLINE; MORPHINE SULFATE; PACLITAXEL; PHOSPHATIDYLCHOLINE; PLACEBO; SMALL INTERFERING RNA; THERMODOX; THERMOSENSITIVE LIPOSOME; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERTEPORFIN; VINCRISTINE; VIROSOME; AMIKACIN; ANTINEOPLASTIC AGENT; ARIKACE; CISPLATIN; EMEPEPIMUT S; ERYTHROMYCIN; FIRTECAN; INX 0076; INX 0125; LIPROSTIN; LURTOTECAN; MITOXANTRONE; NYSTATIN; PLATINUM 1,2 DIAMINOCYCLOHEXANE BISNEODECANOATE; PROSTAGLANDIN E1; RETINOIC ACID; S CKD 602; VINCRISTINE SULFATE;

ALOPECIA; AREA UNDER THE CURVE; B CELL LYMPHOMA; BREAST CANCER; CANCER CHEMOTHERAPY; CARCINOMA; CARDIOTOXICITY; CHEMICAL STRUCTURE; CHEMOTHERAPY INDUCED EMESIS; CRYPTOCOCCAL MENINGITIS; DRUG BLOOD LEVEL; DRUG DOSAGE FORM COMPARISON; DRUG DOSE INCREASE; DRUG FORMULATION; DRUG HALF LIFE; DRUG INDICATION; DRUG RELEASE; DRUG STABILITY; DRUG STORAGE; DRUG TOLERABILITY; ENCAPSULATION; FREEZE DRYING; HAND FOOT SYNDROME; HEART FUNCTION; HEMATOLOGIC MALIGNANCY; HEPATITIS A; HUMAN; INFLUENZA; KAPOSI SARCOMA; LIPID COMPOSITION; LIPOSOMAL DELIVERY; LIVER CELL CARCINOMA; LUNG NON SMALL CELL CANCER; LYMPHOMATOUS MENINGITS; LYOPHILIZED POWDER; MAXIMUM TOLERATED DOSE; MELANOMA; MENINGITIS; MUCOSA INFLAMMATION; MYCOSIS; MYOPIA; NAUSEA; NEOPLASTIC MENINGITIS; NEUROPATHY; NEUROTOXICITY; NEUTROPENIA; NONHUMAN; OCULAR HISTOPLASMOSIS; OVARY CANCER; OVERALL SURVIVAL; PAIN; PANCREAS ADENOCARCINOMA; PARTICLE SIZE; POWDER; PROGRESSION FREE SURVIVAL; RETINA MACULA AGE RELATED DEGENERATION; REVIEW; SEROCONVERSION; SHELF LIFE; SIDE EFFECT; SKIN TOXICITY; STOMATITIS; SURVIVAL RATE; SUSPENSION; THERMOSTABILITY; TRIPLE NEGATIVE BREAST CANCER; UNSPECIFIED SIDE EFFECT; VACCINATION; VISUAL ACUITY; ACUTE LYMPHOBLASTIC LEUKEMIA; ADVANCED CANCER; CANCER SURVIVAL; CARDIOVASCULAR DISEASE; CHEMOTHERAPY INDUCED NAUSEA AND VOMITING; COLORECTAL CANCER; COLORECTAL CARCINOMA; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG SAFETY; HEAD AND NECK CANCER; LEUKEMIA; LIVER CANCER; LUNG CANCER; LUNG INFECTION; LYMPHOMA; MESOTHELIOMA; METASTASIS; MYELOMA; PANCREAS CANCER; PERIPHERAL VASCULAR DISEASE; PROMYELOCYTIC LEUKEMIA; PROSTATE CANCER; SKIN DISEASE; SOLID TUMOR; STOMACH CANCER; SURVIVAL TIME; UTERINE CERVIX CARCINOMA; UVEA MELANOMA; VOMITING;

ANIMALS; ANTINEOPLASTIC AGENTS; CHEMISTRY, PHARMACEUTICAL; HUMANS; LIPOSOMES;

EID: 84856638259     PISSN: 11769114     EISSN: 11782013     Source Type: Journal    
DOI: None     Document Type: Review

References (99)

1. Otake K, Imura T, Sakai H, Abe M. Development of a new preparation method of liposomes using supercritical carbon dioxide. Langmuir. 2001;17(13):3898-3901.
2. Uhumwangho MU, Okor RS. Current trends in the production and biomedical applications of liposomes: a review. Pak J Pharm Sci. 2005; 4(1):9-21.
3. Jiskoot W, Teerlink T, Beuvery EC, Crommelin DJ. Preparation of liposomes via detergent removal from mixed micelles by dilution. The effect of bilayer composition and process parameters on liposome characteristics. Pharm Weekbl Sci. 1986;8(5):259-265.
4. Deamer Q W. Preparation and properties of ether-injection liposomes. Ann N Y Acad Sci. 1978;308:250-258.
5. Szoka F Jr, Papahadjopoulos D. Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci U S A. 1978;75(9):4194-4198.
6. Kim S, Martin GM. Preparation of cell-size unilamellar liposomes with high captured volume and defned size distribution. Biochim Biophys Acta. 1981;646(1):1-9.
7. Meure LA, Foster NR, Dehghani F. Conventional and dense gas techniques for the production of liposomes: a review. AAPS Pharm Sci Tech. 2008;9(3):798-809.
8. Lesoin L, Boutin O, Crampon C, Badens E. CO2/water/surfactant ternary systems and liposome formation using supercritical CO2: a review. Colloid Surface Physicochem Eng Aspect. 2011;377(1-3):1-14.
9. Castor T P. Phospholipid nanosomes. Curr Drug Deliv. 2005;2(4): 329-340.
10. Jesorka A, Orwar O. Liposomes: technologies and analytical applications. Annu Rev Anal Chem (Palo Alto Calif). 2008;1:801-832.
11. Makino K, Shibata A. Chapter 2: Surface properties of liposomes depending on their composition. In: Leitmannova Liu A, editor. Advances in Planar Lipid Bilayers and Liposomes. Netherlands: Elsvier Science; 2006;4:49-77.
12. Irache JM, Esparza I, Gamazo C, Agüeros M, Espuelas S. Nanomedicine: novel approaches in human and veterinary therapeutics. Ve t Parasitol. 2001;180(1-2):47-71.
13. Immordino ML, Dosio F, Cattel L. Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine. 2006;1(3):297-315.
14. Park J W. Liposome-based drug delivery in breast cancer treatment. Breast Cancer Res. 2002;4(3):95-99.
15. Bangham AD. Diffusion of univalent ions across unilamellar of swollen phospholipids. J Mol Biol. 1965;13:238-252.
16. Allen TM, Moase EH. Therapeutic opportunities for targeted liposomal drug delivery. Adv Drug Deliv Rev. 1996;21(2):117-133.
17. ® (Amphotericin B) liposome for injection. Available from: http://www. ambisome.com/. Accessed November 11, 2011.
18. Meunier F, Prentice HG, Ringdén O. Liposomal amphotericin B (AmBisome): safety data from a phase II/III clinical trial. J Antimicrob Chemother. 1991;28 Suppl B:83-91.
19. ® (amphotericin B lipid complex) Injection. Available from: http://enzon. com/. Accessed November 11, 2011.
20. Wasan KM, Lopez-Berestein G. Characteristics of lipid-based formulations that infuence their biological behavior in the plasma of patients. Clin Infect Dis. 1996;23(5):1126-1138.
21. Denning DW, Lee J Y, Hostetler JS, et al. NIAID Mycoses Study Group multicenter trial of oral itraconazole therapy for invasive aspergillosis. Am J Med. 1994;97:135-144.
22. ® Amphotericin B Cholesteryl Sulfate Complex for Injection. Available from: http://www.3riverspharma.com/. Accessed November 11, 2011.
23. ® (daunorubicin citrate liposome injection). Available from: http://www. gilead.com/. Accessed November 11, 2011.
24. Rivera E. Liposomal anthracyclines in metastatic breast cancer: clinical update. Oncologist. 2003;8 Suppl 2:3-9.
25. Tomkinson B, Bendele R, Giles FJ, et al. OSI-211, a novel liposomal topoisomerase I inhibitor, is active in SCID mouse models of human AML and ALL. Leuk Res. 2003;27(11):1039-1050.
26. Hoarau D, Delmas P, David S, Roux E, Leroux JC. Novel long-circulating lipid nanocapsules. Pharm Res. 2004;21(10): 1783-1789.
27. Hong RL. Liposomal anti-cancer drug researches the myth of long circulation. J Chinese Oncol Soc. 2004;20(2):10-21.
28. Gardikis K, Tsimplouli C, Dimas K, Micha-Screttas M, Demetzos C. New chimeric advanced Drug Delivery nano Systems (chi-aDDnSs) as doxorubicin carriers. Int J Pharm. 2010;402(1-2):231-237.
29. Chowdhary RK, Shariff I, Dolphin D. Drug release characteristics of lipid based benzoporphyrin derivative. J Pharm Pharmaceut Sci. 2003;6(1):13-19.
30. Fahr A, van Hoogevest P, May S, Bergstrand N, S Leigh ML. Transfer of lipophilic drugs between liposomal membranes and biological interfaces: consequences for drug delivery. Eur J Pharm Sci. 2005;26(3-4):251-265.
31. ® (verteporfn for injection). Available from: http://www.visudyne.com/. Accessed November 11, 2011.
32. ® (cytarabine liposome injection) Prescribing Information. Available from: http://www.drugs.com/ pro/depocyt.html. Revised Sep 2011. Accessed November 11, 2011.
33. Drugs.com [homepage on the Internet]. DepoDur (morphine sulfate extended-release liposome injection) Prescribing Information. Available from: http://www.drugs.com/pro/depodur.html. Revised Jan 2008. Accessed November 11, 2011.
34. Patil SD, Burgess DJ. Liposomes, design and manufacturing. In: Burgess DJ, editor. Injectable Dispersed Systems: Formulation, Processing and Performance (Drugs and The Pharmaceutical Sciences Series). New York: Marcel Dekker; 2005:249-303.
35. Usonis V, Bakasénas V, Valentelis R, Katiliene G, Vidzeniene D, Herzog C. Antibody titres after primary and booster vaccination of infants and young children with a virosomal hepatitis A vaccine (Epaxal). Vaccine. 2003;21(31):4588-4592.
36. D'Acremont V, Herzog C, Genton B. Immunogenicity and safety of a virosomal hepatitis A vaccine (Epaxal) in the elderly. J Travel Med. 2006;13(2):78-83.
37. The electronic Medicines Compendium (eMC) [homepage on the Internet]. Epaxal Prescribing Information. Available from: http:// www.medicines.org.uk/EMC/medicine/12742/SPC/Epaxal/. Revised January 4, 2011. Accessed November 11, 2011.
38. The electronic Medicines Compendium (eMC) [homepage on the Internet]. INFLEXAL V Prescribing Information. Available from: http://www.medicines.org.uk/emc/medicine/24941/SPC/inflexalv/. Revised Oct 2010. Accessed November 11, 2011.
39. Herzog C, Hartmann K, Künzi V, et al. Eleven years of Inflexal V- a virosomal adjuvanted infuenza vaccine. Vaccine. 2009;27(33): 4381-4387.
40. Zhang JA, Anyarambhatla G, Ma L, et al. Development and characterization of a novel Cremophor EL free liposome-based paclitaxel (LEP-ETU) formulation. Eur J Pharm Biopharm. 2005;59(1): 177-187.
41. Cattaneo AG, Gornati R, Sabbioni E, et al. Nanotechnology and human health: risks and benefits. J Appl Toxicol. 2010;30(8): 730-744.
42. Michaelis U, Haas H. Targeting of cationic liposomes to endothelial tissue. In: Gregoriadis G, editor. Liposome Technology, Volume III: Interactions of Liposomes with the Biological Milieu. London, UK: Informa Healthcare; 2007:151-170.
43. Eichhorn ME, Becker S, Strieth S, et al. Paclitaxel encapsulated in cationic lipid complexes (MBT-0206) impairs functional tumor vascular properties as detected by dynamic contrast enhanced magnetic resonance imaging. Cancer Biol Ther. 2006;5(1):89-96.
44. Robert B, 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):411-429.
45. Li Z, Zhang Y, Wurtz W, et al. Characterization of nebulized liposomal amikacin (Arikace) as a function of droplet size. J Aerosol Med Pulm Drug Deliv. 2008;21(3):245-254.
46. Mossalam M, Dixon AS, Lim CS. Controlling subcellular delivery to optimize therapeutic effect. Ther Deliv. 2010;1(1):169-193.
47. Rodriguez MA, Pytlik R, Kozak T, et al. Vincristine sulfate liposomes injection (Marqibo) in heavily pretreated patients with refractory aggressive non-Hodgkin lymphoma: report of the pivotal phase 2 study. Cancer. 2009;115(15):3475-3482.
48. Krishna R, Webb MS, St Onge G, Mayer LD. Liposomal and non-liposomal drug pharmacokinetics after administration of liposome-encapsulated vincristine and their contribution to drug tissue distribution properties. J Pharmacol Exp Ther. 2001;298(3):1206-1212.
49. Yarmolenko PS, Zhao Y, Landon C, et al. Comparative effects of thermosensitive doxorubicin-containing liposomes and hyperthermia in human and murine tumours. Int J Hyperthermia. 2010;26(5): 485-498.
50. Dromi S, Frenkel V, Luk A, et al. Pulsed-high intensity focused ultrasound and low temperature-sensitive liposomes for enhanced targeted drug delivery and antitumor effect. Clin Cancer Res. 2007;13(9): 2722-2727.
51. Zahid S, Brownell I. Repairing DNA damage in xeroderma pigmentosum: T4N5 lotion and gene therapy. J Drugs Dermatol. 2008;7(4):405-408.
52. Tari AM, Gutiérrez-Puente Y, Monaco G, et al. Liposome-incorporated Grb2 antisense oligodeoxynucleotide increases the survival of mice bearing bcr-abl-positive leukemia xenografts. Int J Oncol. 2007;31(5):1243-1250.
53. Pal A, Khan S, Wang YF, et al. Preclinical safety, pharmacokinetics and antitumor effcacy profle of liposome-entrapped SN-38 formulation. Anticancer Res. 2005;25(1A):331-341.
54. Dragovich T, Mendelson D, Kurtin S, Richardson K, Von Hoff D, Hoos A. A Phase 2 trial of the liposomal DACH platinum L-NDDP in patients with therapy-refractory advanced colorectal cancer. Cancer Chemother Pharmacol. 2006;58(6):759-764.
55. ClinicalTrials.gov [homepage on the Internet]. Prostaglandin E1 (Liprostin) treatment with lower limb angioplasty for peripheral arterial occlusive disease. Available from: http://clinicaltrials.gov/ct2/show/ NCT00053716. Accessed November 11, 2011.
56. Powell E, Chow LQ. BLP-25 liposomal vaccine: a promising potential therapy in non-small-cell lung cancer. Expert Rev Respir Med. 2008;2(1):37-45.
57. Ohyanagi F, Horai T, Sekine I, et al. Safety of BLP25 liposome vaccine (L-BLP25) in Japanese patients with unresectable stage III NSCLC after primary chemoradiotherapy: preliminary results from a Phase I/II study. Jpn J Clin Oncol. 2011;41(5):718-722.
58. Stathopoulos G P, Boulikas T. Lipoplatin formulation review article. J Drug Deliv. 2012;2012:581363.
59. Yu NY, Conway C, Pena RL, Chen JY. STEALTH liposomal CKD-602, a topoisomerase I iInhibitor, improves the therapeutic index in human tumor xenograft models. Anticancer Res. 2007;27(4B):2541-2545.
60. Hwang JH, Lim MC, Seo SS, Park SY, Kang S. Phase II study of belotecan (CKD 602) as a single agent in patients with recurrent or progressive carcinoma of uterine cervix. Jpn J Clin Oncol. 2011;41(5): 624-629.
61. Duffaud F, Borner M, Chollet P, et al. Phase II study of OSI-211 (liposomal lurtotecan) in patients with metastatic or loco-regional recurrent squamous cell carcinoma of the head and neck. An EORTC New Drug Development Group study. Eur J Cancer. 2004;40(18): 2748-2752.
62. Semple SC, Leone R, Wang J, et al. Optimization and characterization of a sphingomyelin/cholesterol liposome formulation of vinorelbine with promising antitumor activity. J Pharm Sci. 2005;94(5):1024-1038.
63. Mross K, Niemann B, Massing U, et al. Pharmacokinetics of lipo-somal doxorubicin (TLC-D99; Myocet) in patients with solid tumors: an open-label, single-dose study. Cancer Chemother Pharmacol. 2004;54(6):514-524.
64. Shaji J, Patole V. Protein and Peptide drug delivery: oral approaches. Indian J Pharm Sci. 2008;70(3):269-277.
65. Chen C, Han D, Cai C, Tang X. An overview of liposome lyophilization and its future potential. J Control Release. 2010;142(3):299-311.
66. EL-Neser OH, Yahiya SA, EL-Gazayerly ON. Effect of formulation design and freeze-drying on properties of fuconazole multilamellar liposomes. Saudi Pharm J. 2010;18:217-224.
67. Clemons K V, Stevens DA. Comparison of fungizone, Amphotec, AmBisome, and Abelcet for treatment of systemic murine cryptococcosis. Antimicrob Agents Chemother. 1998;42(4):899-902.
68. Wu SY, Putral LN, Liang M, et al. Development of a novel method for formulating stable siRNA-loaded lipid particles for in vivo use. Pharm Res. 2009;26(3):512-522.
69. Rahman AM, Yusuf S W, Ewer MS. Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation. Int J Nanomedicine. 2007;2(4):567-583.
70. Lammers T, Hennink WE, Storm G. Tumour-targeted nanomedicines: principles and practice. Br J Cancer. 2008;99(3):392-397.
71. Harris L, Batist G, Belt R, et al. TLC D-99 Study Group. Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as frst-line therapy of metastatic breast carcinoma. Cancer. 2002;94(1):25-36.
72. O'Brien ME, Wigler N, Inbar M, et al. CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable effcacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for frst-line treatment of metastatic breast cancer. Ann Oncol. 2004;15(3):440-449.
73. Hong RL, Tseng YL. Phase I and pharmacokinetic study of a stable, polyethylene-glycolated liposomal doxorubicin in patients with solid tumor. Cancer. 2001;91:1826-1833.
74. Tseng YL, Hong RL, Tao MH, Chang FH. Sterically stabilized anti-idiotype immunoliposomes improve the therapeutic efficacy of doxorubicin in a murine B-cell lymphoma model. Int J Cancer. 1999;80(5):723-730.
75. Chao TC, Wang WS, Yen CC, Chiou TJ, Liu JH, Chen PM. A dose-escalating pilot study of sterically stabilized, pegylated liposomal doxorubicin (Lipo-Dox) in patients with metastatic breast cancer. Cancer Invest. 2003;21(6):837-847.
76. Hossann M, Wang T, Wiggenhorn M, et al. Size of thermosensitive liposomes infuences content release. J Control Release. 2010;147(3): 436-443.
77. ClinicalTrials.gov [homepage on the Internet]. Phase 3 study of ThermoDox with Radiofrequency Ablation (RFA) in Treatment of Hepatocellular Carcinoma (HCC). Available from: http://clinicaltrials. gov/ct2/show/NCT00617981. Accessed November 11, 2011.
78. Mills JK, Needham D. Lysolipid incorporation in dipalmitoylphosphati-dylcholine bilayer membranes enhances the ion permeability and drug release rates at the membrane phase transition. Biochim Biophys Acta. 2005;1716(2):77-96.
79. 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. 2000;60:1197-1201.
80. Banno B, Ickenstein LM, Chiu GN, et al. The functional roles of poly(ethylene glycol)-lipid and lysolipid in the drug retention and release from lysolipid-containing thermosensitive liposomes in vitro and in vivo. J Pharm Sci. 2010;99(5):2295-2308.
81. O'Byrne KJ, Thomas AL, Sharma RA, et al. A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer. Br J Cancer. 2002;87(1):15-20.
82. Forssen EA, Coulter DM, Profftt RT. Selective in vivo localisation of daunorubicin small unilamellar vesicles in solid tumors. Cancer Res. 1992;52(12):3255-3261.
83. ® treatment of solid tumors: preclinical and linical investigations. J Liposome Res. 1994;4(1):481-512.
84. Gill PS, Wernz J, Scadden DT, et al. Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma. J Clin Oncol. 1996;14(8): 2353-2364.
85. Szebeni J. Complement activation-related pseudoallergy: a new class of drug-induced acute immune toxicity. Toxicology. 2005;216:106-121.
86. Mehta RR, Burke TG. Membrane biophysical parameters infuencing anthracycline action. In: Priebe W, editor. Anthracycline Antibiotics. New York: American Chemical Society Publication; 2004:222-240.
87. Fetterly GJ, Straubinger RM. Pharmacokinetics of paclitaxel-containing liposomes in rats. AAPS Pharm Sci. 2003;5(4):E32.
88. Fetterly GJ, Grasela TH, Sherman J W, et al. Pharmacokinetic/ pharmacodynamic modeling and simulation of neutropenia during phase I development of liposome-entrapped paclitaxel. Clin Cancer Res. 2008;14(18):5856-5863.
89. Winer E P, Berry DA, Woolf S, et al. Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: cancer and leukemia group B Trial 9342. J Clin Oncol. 2004;22(11):2061-2068.
90. Bayraktar S, Bayraktar UD, Rocha-Lima CM. Recent developments in palliative chemotherapy for locally advanced and metastatic pancreas cancer. World J Gastroenterol. 2010;16(6):673-682.
91. Stegmann T, Morselt H W, Booy F P, et al. Functional reconstitution of infuenza virus envelopes. EMBO J. 1987;6(9):2651-2659.
92. Glück R, Mischler R, Brantschen S, Just M, Althaus B, Cryz SJ. Immunopotentiating reconstituted infuenza virus virosome vaccine delivery system for immunization against hepatitis A. J Clin Invest. 1992;90(6):2491-2495.
93. Nicholson KG, Thompson CI, Klap JM, et al. Safety and immunoge-nicity of whole-virus, alum-adjuvanted whole-virus, virosomal, and whole-virus intradermal infuenza A/H9N2 vaccine formulations. Vaccine. 2009;28(1):171-178.
94. Kanra G, Marchisio P, Feiterna-Sperling C, et al. Comparison of immu-nogenicity and tolerability of a virosome-adjuvanted and a split infu-enza vaccine in children. Pediatr Infect Dis J. 2004;23(4):300-306.
95. Bressler NM, Bressler SB. Photodynamic therapy with verteporfn (Visudyne): impact on ophthalmology and visual sciences. Invest Ophthalmol Vis Sci. 2000;41(3):624-628.
96. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfn: one-year results of 2 randomized clinical trials - TAP report. Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) Study Group. Arch Ophthalmol. 1999;117:1329-1345.
97. Drugs.com [homepage on the Internet]. MediGene reports additional phase II results of EndoTAG-1 for the treatment of triple receptor-negative breast cancer Prescribing Information. Available from: http:// www.drugs.com/clinical_trials/medigene-reports-additional-phase-ii-results-endotag-1-triple-receptor-negative-breast-cancer-9689.html. Posted Jun 2010. Accessed November 15, 2011.
98. White SC, Lorigan P, Margison G P, et al. Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer. Br J Cancer. 2006;95(7):822-828.
99. Booser DJ, Esteva FJ, Rivera E, et al. Phase II study of liposomal annamycin in the treatment of doxorubicin-resistant breast cancer. Cancer Chemother Pharmacol. 2002;50(1):6-8.