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Cationic liposomal drug delivery system for specific targeting of human cd14+ monocytes in whole blood

A cationic lipid and liposome technology, applied in liposome delivery, cardiovascular system diseases, antibacterial drugs, etc.

Inactive Publication Date: 2015-06-10
碧奥尼尔股份公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Systemically administered anti-inflammatory drugs have adverse side effects + localize to healthy tissue or are rapidly excreted, a problem that can be prevented by using specific delivery systems

Method used

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  • Cationic liposomal drug delivery system for specific targeting of human cd14+ monocytes in whole blood
  • Cationic liposomal drug delivery system for specific targeting of human cd14+ monocytes in whole blood
  • Cationic liposomal drug delivery system for specific targeting of human cd14+ monocytes in whole blood

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0152] Liposome preparation

[0153] Monolamellar fully hydrated liposomes are composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate Glycerol (POPG), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly Ethylene glycol)-2000] (DOPE-PEG2000) mixture. As a fluorescent label to determine the presence of liposomes in biological systems, 0.5% 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-rhodamine (DOPE-RhB) was combined with lipid as tracer mix. Summarize the molar ratio of each lipid in the liposomes in figure 1 In A. All lipids were obtained from Avanti Polar lipids. Briefly, weighed appropriate amounts of POPC, POPG, DOTAP and DOPE-PEG2000 were dissolved in chloroform. by Moderate N 2 The solvent was removed by airflow and the lipid film was dried overnight at low pressure to remove traces of solvent. Multilamellar liposomes were prepared by dispers...

Embodiment 2

[0155] Characterization of composition-dependent liposome size and surface charge

[0156] Preparations such as figure 1 Liposomes prepared are summarized in A. We designed liposomes with 0-50% net positive charge ( figure 1 Formulations 6-12 in A) were compared with negatively or nearly neutrally charged control liposomes ( figure 1 Formulations 1-5 in A). Liposomes were prepared as described in Example 1 and prepared in MilliQ water from 300 mM glucose, 10 mM HEPES, 1 mM CaCl by dynamic light scattering using a ZetaPALS zeta potential analyzer from Brookhaven Instruments. 2 Their size in nanometers (nm) was determined in a pH 7.4 buffer solution. Liposomes show a diameter of 110 ± 20nm ( figure 1 B). The surface charge (zeta potential) of the liposomes was measured in mV and it was shown that the surface charge is dependent on the lipid composition ( figure 1 C). The addition of negatively charged POPG (10 mol%) to liposomes revealed a negative surface charge of -13m...

Embodiment 3

[0158] Liposome composition-dependent targeting of liposomes to monocytes

[0159] Cellular uptake of improved POPC liposome formulations was determined based on the fluorescence of RhB incorporated into the liposomal membrane. The total amount of cell-associated liposomes (expressed as 'uptake' and including cell membrane-associated liposomes and liposomes that have been internalized) was assessed using excitation at 532 nm and emission at 564-606 nm. . Liposome uptake in 5 different cell populations in whole blood was analyzed. The following markers were used to differentiate the different populations: CD14 (monocyte marker), CD15 (granulocyte marker), CD3 (T-lymphocyte marker), CD19 (B-lymphocyte marker) and CD56 (natural killer cell marker). Whole blood was obtained from healthy volunteers by standard methods using BD vacuum blood collection tubes containing ethylenediaminetetraacetic acid (EDTA, 366450). Briefly, 10 μl of liposome formulation ( figure 1 Formulations 1...

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Abstract

This invention concerns a liposome comprising lipids and at least one active ingredient, wherein at least one of the lipids is a cationic lipid; said liposome exhibiting a net positive charge at physiological conditions at which said liposome preferentially adheres to monocytes in freshly drawn blood when compared to adherence to granulocytes, T-lymphocytes, B-lymphocytes and / or NK cells in freshly drawn blood, to a lipid-based pharmaceutical composition comprising said liposomes and their use in monocytic associated prophylaxis, treatment or amelioration of a condition such as cancer, an infectious disease, an inflammatory disease, an autoimmune disease or allergy.

Description

field of invention [0001] The present invention relates to specific delivery using cationic liposomes. More specifically, the present invention relates to liposomes comprising lipids and at least one active ingredient, wherein at least one lipid is a cationic lipid; said liposomes exhibit a net positive charge under physiological conditions when the Said liposome preferentially adheres to monocytes in freshly drawn blood; the present invention also relates to a lipid-based pharmaceutical composition comprising said liposome and its use in the prevention, treatment or improvement of diseases associated with monocytes Applications. Background of the invention [0002] Liposomes are lipid vesicles composed of a lipid bilayer enclosing an aqueous core. These vesicles are considered to have great potential as drug delivery systems for several reasons: i) can deliver different types of drugs; can load hydrophilic drugs into aqueous compartments or can anchor hydrophobic drugs to...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61P35/02
CPCA61K31/203A61K31/43A61K31/505A61K31/573A61K31/593A61K31/635A61K38/14A61K9/1272A61P1/00A61P1/04A61P1/16A61P11/00A61P11/06A61P11/14A61P13/12A61P15/02A61P17/00A61P17/02A61P17/04A61P19/02A61P21/04A61P25/00A61P27/02A61P27/16A61P29/00A61P31/00A61P31/04A61P31/10A61P31/14A61P31/16A61P33/00A61P33/06A61P33/12A61P35/00A61P35/02A61P35/04A61P37/02A61P37/06A61P37/08A61P43/00A61P7/06A61P7/08A61P9/00A61P3/10Y02A50/30A61K39/0011A61K45/00A61K47/24
Inventor S·S·杰森T·L·安德森J·R·汉利克森P·T·杰汉森
Owner 碧奥尼尔股份公司
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