Liposome encapsulated affinity drug
A liposome and affinity technology, applied in liposome delivery, drug combination, drug delivery, etc., can solve the problem of losing the advantage of antifolates
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Embodiment 1
[0154] Example 1: Production of folate receptor alpha targeting liposomes containing pemetrexed and hapten
[0155] Production of Pemetrexed Liposomes
[0156] Pemetrexed disodium heptahydrate (ALIMTA) is highly water soluble with a solubility of 100 mg / ml at neutral pH. Pemetrexed was encapsulated in liposomes by the following steps. First, the lipid components of the liposome membranes are weighed and combined as a concentrated solution in ethanol at about 65°C. In this example, the lipids used were hydrogenated soybean phosphatidylcholine, cholesterol, DSPE-PEG-2000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy base (polyethylene glycol)-2000]), PEG-DSPE-maleimide and PEG-DSPE-FITC. The molar ratio of HSPC:cholesterol:PEG-DSPE is about 55:40:5. Next, pemetrexed was dissolved in an aqueous buffer at a concentration of 100 mg / ml. The drug solution was heated to 65°C. Inject the ethanolic lipid solution into the pemetrexed solution using a small-bore ne...
Embodiment 2
[0166] Example 2: Cell lines used in experiments
[0167] Cell lines used in experiments are commercially available from sources such as ATCC (American Type Culture Collection, Manassas, VA, USA). The cell lines, their ATCC accession numbers and growth conditions are listed below.
[0168] Calu-3 (ATCC HTB-55); EMEM (Cat. #30-2003); 10% HI FBS; 1% Pen / Strep; 1% L-Glutamine.
[0169] KB; EMEM (Cat. #30-2003); 10% HI FBS; 1% Pen / Strep; 1% L-Glutamine.
[0170] CCD841 (ATCC CRL-1790); EMEM (Cat. #30-2003); 10% HI FBS; 1% Pen / Strep; 1% L-Glutamine.
[0171] Hs578Bst (ATCC HTB-125); Hybri-Care medium pH 7.0 (Cat. #46-X); 30 ng / ml mouse EGF; 10% HI FBS; 1% Pen / Strep;
[0172] NCI-H2087 (ATCC CRL-5922); RPMI-1640 (Cat. #30-2001); 5% HI FBS; 1% Pen / Strep; 1% L-Glutamine.
[0173] NCI-H2452 (ATCC CRL-5946); RPMI-1640 (Cat. #30-2001); 10% HI FBS; 1% Pen / Strep; 1% L-Glutamine.
[0174] OVCAR-3 (ATCC HTB-161); RPMI-1640 (Cat. #30-2001); 20% HI FBS; 1% Pen / Strep; 1% L-Glutamine.
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Embodiment 3
[0178] Example 3: Determining the binding specificity of a sample construct
[0179] The level of folate receptor alpha on the cell surface was measured by flow cytometry using a monoclonal antibody conjugated to a fluorescent dye. Lines prior to antibody treatment (see e.g. Figure 6 , lines 602 and 604) compared to after antibody binding (see e.g. Figure 6 , line 606) indicates detection of the receptor by flow cytometry. Histogram (eg, Figure 6 , line 606) relative to untreated cells (see e.g. Figure 6 , lines 602 and 604) shift to the more to the right, the higher the level of receptors on the cell surface. The figure shows high levels of folate receptor alpha on cancer cells, but barely detectable levels on normal cells.
[0180] Exemplary liposomes, as part of an exemplary liposome composition constructed, bind to the cell surface of cells that are folate receptor alpha positive but not folate receptor alpha negative. Exemplary liposomes contain antibodies to ...
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