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

Figures & data

Table 1 Liposome-based drugs on market

Product name	Route of injection	Drug	Particle type/size	Drug form/Storage time	Lipid composition	Approved indication	Ref
Ambisome	Intravenous	Amphotericin B	Liposome	Powder/36 months	HSPC, DSPG, cholesterol, and amphoteracin B (2:0.8:1:0.4 molar ratio)	Sever fungal infections	^Citation13,Citation17,Citation18
Abelcet	Intravenous	Amphotericin B	Lipid complex	Suspension/24 months	DMPC and DMPG (7:3 molar ratio)	Sever fungal infections	^Citation19,Citation20
Amphotec	Intravenous	Amphotericin B	Lipid complex	Powder/24 months	Cholesteryl sulfate	Sever fungal infections	^Citation21,Citation22
DaunoXome	Intravenous	Daunorubicin	Liposome	Emulsion/12 months	DSPC and cholesterol (2:1 molar ratio)	Blood tumors	^Citation13,Citation23–Citation25
Doxil	Intravenous	Doxorubicin	PEGylated liposome	Suspension/20 months	HSPC, cholesterol, and PEG 2000-DSPE (56:39:5 molar ratio)	Kaposi’s sarcoma, Ovarian/breast cancer	^Citation13,Citation14,Citation26
Lipo-dox	Intravenous	Doxorubicin	PEGylated liposome	Suspension/36 months	DSPC, cholesterol, and PEG 2000-DSPE (56:39:5 molar ratio)	Kaposi’s sarcoma, ovarian/breast cancer	^Citation27
Myocet	Intravenous	Doxorubicin	Liposome	Powder/18 months	EPC and cholesterol (55:45 molar ratio)	Combination therapy with cyclophosphamide in metastatic breast cancer	^Citation13,Citation14,Citation28
Visudyne	Intravenous	Verteporfin	Liposome	Powder/48 months	EPG and DMPC (3:5 molar ratio)	Age-related molecular degerneration, pathologic myopia, ocular histoplasmosis	^Citation29^–^Citation31
Depocyt	Spinal	Cytarabine	Liposome	Suspension/18 months	Cholesterol, Triolein, DOPC, and DPPG (11:1:7:1 molar ratio)	Neoplastic meningitis and lymphomatous meningitis	^Citation13,Citation32
DepoDur	Epidural	Morphine sulfate	Liposome	Suspension/24 months	Cholesterol, Triolein, DOPC, and DPPG (11:1:7:1 molar ratio)	Pain management	^Citation33,Citation34
Epaxal	Intramuscular	Inactivated hepatitis A virus (strain RG-SB)	Liposome	Suspension/36 months	DOPC and DOPE	Hepatitis A	^Citation35^–^Citation37
Inflexal V	Intramuscular	Inactivated hemaglutinine of Influenza virus strains A and B	Liposome	Suspension/12 months	DOPC and DOPE	Influenza	^Citation38,Citation39

Abbreviations: DOPE, dioleoylphosphatidylethanolamine; DOPC, dioleoylphosphatidylcholine; DPPG, dipalmitoylphosphatidylglycerol; HSPG, hydrogenated soy phosphatidylcholine; DSPG, distearoylphosphatidylglycerol; EPC, egg phosphatidylcholine; DSPC, distearoylphosphatidylcholine; DMPC, 1-α-dimyristoylphosphatidylcholine; DMPG, l-α-dimyristoylphosphatidylglycerol; EPG, egg phosphatidylglycerol; PEG 2000-DSPE, polyethylene glycol 2000-distearoyl-phosphatidylethanolamine.

Table 2 Liposome-based drugs in clinical trials

Product name	Route of injection	Drug	Lipid composition	Approved indication	Trial phase	Ref
LEP-ETU (powder/12 months)	Intravenous	Paclitaxel	DOPC, cholesterol, and cardiolipin (90:5:5 molar ratio)	Ovarian, breast, and lung cancers	Phase I/II	^Citation13,Citation40
LEM-ETU	Intravenous	Mitoxantrone	DOPC, cholesterol, and cardiolipin in 90:5:5 molar ratio	Leukemia, breast, stomach, liver, ovarian cancers	Phase I	^Citation13,Citation41
EndoTAG-1 (powder/24 months)	Intravenous	Paclitaxel	DOTAP, DOPC, and paclitaxel (50:47:3 molar ratio)	Anti-angiogenic properties, breast cancer, pancreatic caner	Phase II	^Citation13,Citation42–Citation44
Arikace	Portable aerosol delivery	Amikacin	DPPC and cholesterol	Lung infection	Phase III	^Citation45,Citation46
Marqibo	Intravenous	Vincristine	Cholesterol and egg sphingomyelin (45:55 molar ratio)	Metastatic malignant uveal melanoma	Phase III	^Citation13,Citation47,Citation48
ThermoDox	Intravenous	Doxorubicin	DPPC, MSPC, and PEG 2000-DSPE (90:10:4 molar ratio)	Non-resectable hepatocellular carcinoma	Phase III	^Citation49,Citation50
Atragen	Intravenous	Tretinoin	DMPC and soybean oil	Acute promyelocytic leukemia, hormone-refractory prostate cancer	Phase II	^Citation13
T4N5 liposome lotion	Topical	Bacteriophage T4 endonuclease 5	Unknown	Xeroderma pigmentosum.	Phase III	^Citation51
Liposomal Grb-2	Intravenous	Grb2 antisense oligodeoxynucleotide	Unknown	Acute myeloid leukemia, chronic myelogenous leukemia, acute lymphoblastic leukemia	Phase I	^Citation52
Nyotran	Intravenous	Nystatin	DMPC, DMPG, and cholesterol	Systemic fungal infections	Phase I/II	^Citation13
LE-SN38	Intravenous	SN-38, the active metabolite of irinotecan	DOPC, cholesterol, and cardiolipin	Metastatic colorectal cancer	Phase I/II	^Citation13,Citation53
Aroplatin	Intrapleural	Cisplatin analog (L-NDDP)	DMPC and DMPG	Metastatic colorectal carcinoma	Phase II	^Citation54
Liprostin	Intravenous	Prostaglandin E1	Unknown	Peripheral vascular disease	Phase II/III	^Citation55
Stimuvax	Subcutaneous	BLP25 lipopeptide (MUC1-targeted peptide)	Monophosphoryl lipid A, cholesterol, DMPG, and DPPC	Cancer vaccine for multiple myeloma developed encephalitis	Phase III	^Citation56,Citation57
SPI-077	Intravenous	Cisplatin	SHPC, cholesterol, and DSPE-PEG	Head and neck cancer, lung cancer	Phase I/II	^Citation13
Lipoplatin (suspension/36 months)	Intravenous	Cisplatin	SPC, DPPG, cholesterol, and mPEG 2000-DSPE	Pancreatic cancer, head and neck cancer, mesothelioma, breast and gastric cancer, and non-squamous non-small-cell lung cancer	Phase III	^Citation13,Citation58
S-CKD602	Intravenous	Camptothecin analog	DPSC and DSPE-PEG (95:5 molar ratio)	Recurrent or progressive carcinoma of the uterine cervix	Phase I/II	^Citation13,Citation59,Citation60
OSI-211	Intravenous	Lurtotecan	HSPC and cholesterol (2:1 molar ratio)	Ovarian cancer, head, and neck cancer	Phase II	^Citation25,Citation61
INX-0125	Intravenous	Vinorelbine	Cholesterol and egg sphingomyelin (45:55 molar ratio)	Advanced solid tumors	Phase I	^Citation13,Citation62
INX-0076	Intravenous	Topotecan	Cholesterol and egg sphingomyelin (45:55 molar ratio)	Advanced solid tumors	Phase I	^Citation13
Liposome-annamycin (powder)	Intravenous	Annamycin	DSPC, DSPG, and Tween	Acute lymphocytic leukemia	Phase I/II	^Citation13

Abbreviations: DOPC, 1,2-Dioleoyl-sn-glycero-3-phosphocholine; MSPC, monostearoylphosphatidylcholine; DPPC, dipalmitoylphosphatidylcholine; DOTAP, 1,2 dioleoyl-3-trimethylammonium-propane; SPC, soy phosphatidylcholine; mPEG 2000-DSPE, methoxy-polyethylene glycol-distearoyl phosphatidylethanolamine, DSPE, distearoylphosphatidylethanolamine.

Figure 1 Chemical structures of lipids in liposome formulations.

Abbreviations: DOTAP, 1,2-dioleoyl-3-trimethylammonium propane; DPPC, dipalmitoylphosphatidylcholine; DOPA, 1,2-Dioleoyl-sn-Glycero-3-Phosphate; MSPC, monostearoylphosphatidylcholine; DPPG, dipalmitoylphosphatidylglycerol; DSPC, distearoylphosphatidylcholine; HSPC, hydrogenated soy PC; DMPG, l-α-dimyristoylphosphatidylglycerol; DMPC, 1-α-dimyristoylphosphatidylcholine; DOPC, 1,2-Dioleoyl-sn-glycero-3-phosphocholine; DOPE, dioleoyl phosphatidylethanolamine; DSPG, distearoylphosphatidylglycerol; PEG2000-DSPE, polyethylene glycol 2000-distearoylphosphatidylethanolamine.

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