DK2510921T3 - Nanoemulsions of perfluorocarbon with endocytosis-enhancing surface for gene transfer - Google Patents
Nanoemulsions of perfluorocarbon with endocytosis-enhancing surface for gene transfer Download PDFInfo
- Publication number
- DK2510921T3 DK2510921T3 DK12171341.6T DK12171341T DK2510921T3 DK 2510921 T3 DK2510921 T3 DK 2510921T3 DK 12171341 T DK12171341 T DK 12171341T DK 2510921 T3 DK2510921 T3 DK 2510921T3
- Authority
- DK
- Denmark
- Prior art keywords
- nanoemulsion
- component
- perfluorocarbon
- sirna
- endocytosis
- Prior art date
Links
- 239000007908 nanoemulsion Substances 0.000 title claims description 53
- 108090000623 proteins and genes Proteins 0.000 title claims description 38
- 238000012546 transfer Methods 0.000 title claims description 27
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 title claims description 8
- 108020004459 Small interfering RNA Proteins 0.000 claims description 58
- 230000012202 endocytosis Effects 0.000 claims description 26
- 102000004169 proteins and genes Human genes 0.000 claims description 22
- 230000002708 enhancing effect Effects 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 21
- 102000004338 Transferrin Human genes 0.000 claims description 17
- 108090000901 Transferrin Proteins 0.000 claims description 17
- 239000002245 particle Substances 0.000 claims description 17
- 150000001875 compounds Chemical class 0.000 claims description 15
- 239000012581 transferrin Substances 0.000 claims description 15
- 230000001804 emulsifying effect Effects 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 150000003904 phospholipids Chemical class 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 10
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 8
- 150000002433 hydrophilic molecules Chemical class 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 7
- 239000007795 chemical reaction product Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 238000000338 in vitro Methods 0.000 claims description 6
- 238000001727 in vivo Methods 0.000 claims description 6
- 239000000872 buffer Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 150000002632 lipids Chemical class 0.000 claims description 5
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 230000004700 cellular uptake Effects 0.000 claims description 4
- 235000012000 cholesterol Nutrition 0.000 claims description 4
- 239000012634 fragment Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- WTWWXOGTJWMJHI-UHFFFAOYSA-N perflubron Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)Br WTWWXOGTJWMJHI-UHFFFAOYSA-N 0.000 claims description 4
- 229960001217 perflubron Drugs 0.000 claims description 4
- -1 perfluorocarbon compound Chemical class 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 3
- 239000008346 aqueous phase Substances 0.000 claims description 3
- 108091070501 miRNA Proteins 0.000 claims description 3
- 239000002679 microRNA Substances 0.000 claims description 3
- 150000003431 steroids Chemical class 0.000 claims description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 2
- 229960001231 choline Drugs 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 229940031098 ethanolamine Drugs 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 claims description 2
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical group O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims description 2
- RVZRBWKZFJCCIB-UHFFFAOYSA-N perfluorotributylamine Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)N(C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F RVZRBWKZFJCCIB-UHFFFAOYSA-N 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 229960001153 serine Drugs 0.000 claims description 2
- 239000011782 vitamin Substances 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 235000013343 vitamin Nutrition 0.000 claims description 2
- 229930003231 vitamin Natural products 0.000 claims description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims 2
- RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 claims 2
- 239000003623 enhancer Substances 0.000 claims 2
- SLKDGVPOSSLUAI-PGUFJCEWSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCCCCCC SLKDGVPOSSLUAI-PGUFJCEWSA-N 0.000 claims 1
- 101100135744 Caenorhabditis elegans pch-2 gene Proteins 0.000 claims 1
- 239000002539 nanocarrier Substances 0.000 description 48
- 230000036772 blood pressure Effects 0.000 description 35
- 241001465754 Metazoa Species 0.000 description 33
- 102000004881 Angiotensinogen Human genes 0.000 description 17
- 108090001067 Angiotensinogen Proteins 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 15
- 241000699670 Mus sp. Species 0.000 description 14
- 239000000839 emulsion Substances 0.000 description 11
- 230000004872 arterial blood pressure Effects 0.000 description 10
- 230000036760 body temperature Effects 0.000 description 10
- 239000000126 substance Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 238000010253 intravenous injection Methods 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 230000032258 transport Effects 0.000 description 7
- 210000003494 hepatocyte Anatomy 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 5
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 5
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 5
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 5
- 229960000830 captopril Drugs 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 206010002091 Anaesthesia Diseases 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 230000037005 anaesthesia Effects 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 210000000805 cytoplasm Anatomy 0.000 description 4
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 4
- 210000001163 endosome Anatomy 0.000 description 4
- 230000036454 renin-angiotensin system Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 102100028255 Renin Human genes 0.000 description 3
- 108090000783 Renin Proteins 0.000 description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 238000000265 homogenisation Methods 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 3
- 235000019799 monosodium phosphate Nutrition 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 238000002525 ultrasonication Methods 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- 101800000733 Angiotensin-2 Proteins 0.000 description 2
- 102400000345 Angiotensin-2 Human genes 0.000 description 2
- 102000015427 Angiotensins Human genes 0.000 description 2
- 108010064733 Angiotensins Proteins 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 2
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- 238000001493 electron microscopy Methods 0.000 description 2
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 108010045676 holotransferrin Proteins 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 2
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 230000029865 regulation of blood pressure Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 101800000734 Angiotensin-1 Proteins 0.000 description 1
- 102400000344 Angiotensin-1 Human genes 0.000 description 1
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 description 1
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 235000001815 DL-alpha-tocopherol Nutrition 0.000 description 1
- 239000011627 DL-alpha-tocopherol Substances 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000002802 cardiorespiratory effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 239000002961 echo contrast media Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000004401 flow injection analysis Methods 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 208000012866 low blood pressure Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000003303 reheating Methods 0.000 description 1
- 230000036391 respiratory frequency Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/40—Transferrins, e.g. lactoferrins, ovotransferrins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dispersion Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08156434A EP2123256A1 (en) | 2008-05-19 | 2008-05-19 | Perfluorcarbon nanoemulsions with endocytosis enhancing surface for gene-transfer |
| EP09749747A EP2285349B1 (en) | 2008-05-19 | 2009-05-13 | Perfluorcarbon nanoemulsions with endocytosis enhancing surface for gene-transfer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2510921T3 true DK2510921T3 (en) | 2017-10-23 |
Family
ID=39869983
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK12171341.6T DK2510921T3 (en) | 2008-05-19 | 2009-05-13 | Nanoemulsions of perfluorocarbon with endocytosis-enhancing surface for gene transfer |
| DK09749747.3T DK2285349T3 (da) | 2008-05-19 | 2009-05-13 | Perfluorcarbonnanoemulsioner med endocytosefremmende overflade til genoverførsel |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK09749747.3T DK2285349T3 (da) | 2008-05-19 | 2009-05-13 | Perfluorcarbonnanoemulsioner med endocytosefremmende overflade til genoverførsel |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US9616131B2 (https=) |
| EP (3) | EP2123256A1 (https=) |
| JP (1) | JP5546534B2 (https=) |
| CN (2) | CN102847170B (https=) |
| AU (1) | AU2009249812B2 (https=) |
| CA (1) | CA2725513C (https=) |
| DK (2) | DK2510921T3 (https=) |
| ES (2) | ES2391375T3 (https=) |
| HU (1) | HUE035320T2 (https=) |
| IL (1) | IL209205A (https=) |
| NZ (1) | NZ589417A (https=) |
| PL (2) | PL2510921T3 (https=) |
| WO (1) | WO2009141257A1 (https=) |
| ZA (1) | ZA201008274B (https=) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2123256A1 (en) | 2008-05-19 | 2009-11-25 | Ruhr-Universität Bochum | Perfluorcarbon nanoemulsions with endocytosis enhancing surface for gene-transfer |
| US20140065223A1 (en) * | 2011-03-31 | 2014-03-06 | Jeanette Libera-Koerner | Perfluorinated compounds for the non-viral transfer of nucleic acids |
| CN103263695B (zh) * | 2013-05-17 | 2014-10-29 | 中国人民解放军第四军医大学 | 全氟三乙胺乳液与种子细胞复合的神经导管制备方法 |
| CN103251980B (zh) * | 2013-05-17 | 2014-07-02 | 中国人民解放军第四军医大学 | 全氟三丁胺与纤维蛋白水凝胶复合的神经导管制备方法 |
| EP2853595A1 (en) | 2013-09-30 | 2015-04-01 | Soluventis GmbH | NOTCH 1 specific siRNA molecules |
| CN110177575B (zh) * | 2016-12-01 | 2024-02-13 | 国立大学法人埼玉大学 | 药物递送系统用胞吞作用增强剂 |
| WO2025080939A1 (en) | 2023-10-13 | 2025-04-17 | Ultragenyx Pharmaceutical, Inc. | Compositions and methods for treating conditions associated with cartilage oligomeric matrix protein (comp) mutations |
| WO2025128853A2 (en) | 2023-12-13 | 2025-06-19 | Ultragenyx Pharmaceutical Inc. | Compositions and methods for treating conditions associated with ube3a overexpression |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6050578B2 (ja) | 1981-12-25 | 1985-11-09 | 日本スチレンペ−パ−株式会社 | 合成樹脂発泡体の製造法 |
| FR2720943B1 (fr) | 1994-06-09 | 1996-08-23 | Applic Transferts Technolo | Emulsions inverses stables à forte concentration en composé(s) fluoré(s) et leur utilisation pour l'administration pulmonaire de médicaments et pour la fabrication d'émulsions multiples. |
| US6071890A (en) | 1994-12-09 | 2000-06-06 | Genzyme Corporation | Organ-specific targeting of cationic amphiphile/DNA complexes for gene therapy |
| US5667809A (en) | 1995-06-07 | 1997-09-16 | Alliance Pharmaceutical Corp. | Continuous fluorochemical microdispersions for the delivery of lipophilic pharmaceutical agents |
| PL323931A1 (en) * | 1995-06-07 | 1998-04-27 | Alliance Pharma | Compositions of reversed emulsion of fluorine derivatives of hydrocarbons for use as drug delivering carriers |
| JP2001002592A (ja) | 1999-06-18 | 2001-01-09 | Dai Ichi Seiyaku Co Ltd | 遺伝子導入用組成物 |
| KR100872884B1 (ko) | 2000-03-24 | 2008-12-10 | 바이오스피어 메디칼 인코포레이티드 | 능동 색전화용 미소구 |
| US20020155084A1 (en) * | 2000-06-02 | 2002-10-24 | The Regents Of The University Of The Michigan | Nanoemulsion formulations |
| WO2002007717A1 (en) * | 2000-07-20 | 2002-01-31 | Otkrytoe Aktsionernoe Obschestvo Nauchno-Proizvodstvennaya Firma 'perftoran' | Emulsion of perfluororganic compounds for medical purposes, method for producing said emulsion and methods for curing and preventing diseases with the aid of the emulsion |
| CA2452471C (en) | 2001-07-10 | 2010-06-29 | Michael N. Davidson | Enhancement of transfection of dna into the liver |
| US20040115159A1 (en) | 2002-03-29 | 2004-06-17 | Tadlock Charles C | Novel nanoemulsions |
| GB0408164D0 (en) | 2004-04-13 | 2004-05-19 | Immune Targeting Systems Ltd | Antigen delivery vectors and constructs |
| US20070184076A1 (en) | 2006-02-07 | 2007-08-09 | Unger Evan C | Liquid-filled nanodroplets for anti-cancer therapy |
| EP1844772A1 (en) | 2006-04-06 | 2007-10-17 | Polyplus-Transfection SA | Compositions for transfection of oligonucleotides active for gene silencing and their biological and therapeutical applications |
| EP2123256A1 (en) | 2008-05-19 | 2009-11-25 | Ruhr-Universität Bochum | Perfluorcarbon nanoemulsions with endocytosis enhancing surface for gene-transfer |
-
2008
- 2008-05-19 EP EP08156434A patent/EP2123256A1/en not_active Withdrawn
-
2009
- 2009-05-13 AU AU2009249812A patent/AU2009249812B2/en not_active Ceased
- 2009-05-13 PL PL12171341T patent/PL2510921T3/pl unknown
- 2009-05-13 HU HUE12171341A patent/HUE035320T2/en unknown
- 2009-05-13 CN CN201210345209.2A patent/CN102847170B/zh not_active Expired - Fee Related
- 2009-05-13 NZ NZ589417A patent/NZ589417A/en not_active IP Right Cessation
- 2009-05-13 ES ES09749747T patent/ES2391375T3/es active Active
- 2009-05-13 ES ES12171341.6T patent/ES2642316T3/es active Active
- 2009-05-13 JP JP2011509929A patent/JP5546534B2/ja not_active Expired - Fee Related
- 2009-05-13 EP EP09749747A patent/EP2285349B1/en active Active
- 2009-05-13 WO PCT/EP2009/055779 patent/WO2009141257A1/en not_active Ceased
- 2009-05-13 EP EP12171341.6A patent/EP2510921B1/en active Active
- 2009-05-13 PL PL09749747T patent/PL2285349T3/pl unknown
- 2009-05-13 CA CA2725513A patent/CA2725513C/en active Active
- 2009-05-13 DK DK12171341.6T patent/DK2510921T3/en active
- 2009-05-13 CN CN200980118149.7A patent/CN102112109B/zh not_active Expired - Fee Related
- 2009-05-13 US US12/992,280 patent/US9616131B2/en not_active Expired - Fee Related
- 2009-05-13 DK DK09749747.3T patent/DK2285349T3/da active
-
2010
- 2010-11-09 IL IL209205A patent/IL209205A/en active IP Right Grant
- 2010-11-18 ZA ZA2010/08274A patent/ZA201008274B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN102847170A (zh) | 2013-01-02 |
| CN102112109B (zh) | 2016-10-12 |
| EP2285349B1 (en) | 2012-07-11 |
| PL2285349T3 (pl) | 2012-12-31 |
| HK1179533A1 (zh) | 2013-10-04 |
| PL2510921T3 (pl) | 2017-12-29 |
| DK2285349T3 (da) | 2012-10-22 |
| EP2510921A1 (en) | 2012-10-17 |
| HK1159479A1 (zh) | 2012-08-03 |
| IL209205A (en) | 2015-08-31 |
| ZA201008274B (en) | 2012-02-29 |
| CA2725513C (en) | 2013-07-02 |
| EP2510921B1 (en) | 2017-07-12 |
| WO2009141257A1 (en) | 2009-11-26 |
| ES2391375T3 (es) | 2012-11-23 |
| CA2725513A1 (en) | 2009-11-26 |
| JP2011520936A (ja) | 2011-07-21 |
| CN102847170B (zh) | 2016-03-16 |
| NZ589417A (en) | 2012-03-30 |
| AU2009249812A1 (en) | 2009-11-26 |
| IL209205A0 (en) | 2011-01-31 |
| EP2285349A1 (en) | 2011-02-23 |
| AU2009249812B2 (en) | 2013-08-22 |
| HUE035320T2 (en) | 2018-05-02 |
| US20110091561A1 (en) | 2011-04-21 |
| CN102112109A (zh) | 2011-06-29 |
| US9616131B2 (en) | 2017-04-11 |
| JP5546534B2 (ja) | 2014-07-09 |
| EP2123256A1 (en) | 2009-11-25 |
| ES2642316T3 (es) | 2017-11-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2510921T3 (en) | Nanoemulsions of perfluorocarbon with endocytosis-enhancing surface for gene transfer | |
| JP7600208B2 (ja) | 拘束された脂質を含むナノ材料およびその使用 | |
| Ding et al. | A biomimetic nanovector-mediated targeted cholesterol-conjugated siRNA delivery for tumor gene therapy | |
| JP5571308B2 (ja) | 両性リポソームにおけるまたはそれに関する改善 | |
| Dakwar et al. | Delivery of proteins to the brain by bolaamphiphilic nano-sized vesicles | |
| Gao et al. | H 2 O 2-responsive and plaque-penetrating nanoplatform for mTOR gene silencing with robust anti-atherosclerosis efficacy | |
| CN102824647A (zh) | 基于小核酸药物成骨治疗的骨靶向递送系统及其制备方法 | |
| Qian et al. | Low density lipoprotein mimic nanoparticles composed of amphipathic hybrid peptides and lipids for tumor-targeted delivery of paclitaxel | |
| Li et al. | Optimal delivery strategies for nanoparticle-mediated mRNA delivery | |
| EP3544595A1 (en) | Particles comprising surfactant protein b and one or more lipids | |
| Yamamoto et al. | Failure of active targeting by a cholesterol-anchored ligand and improvement by altering the lipid composition to prevent ligand desorption | |
| EP4349328A1 (en) | Lipoprotein-mimicking solid lipid nanoparticles for drug delivery and uses thereof | |
| HK1159479B (en) | Perfluorcarbon nanoemulsions with endocytosis enhancing surface for gene-transfer | |
| WO2023133546A2 (en) | Folding mrna into a nanoscale delivery vehicle | |
| CN118695875A (zh) | 在用于治疗和/或预防疾病的方法中使用的制剂 | |
| HK1179533B (en) | Perfluorcarbon nanoemulsions with endocytosis enhancing surface for gene-transfer | |
| CN117460537A (zh) | 核酸递送 | |
| WO2006080452A1 (ja) | 水溶性物質で表面修飾された微粒子の製造方法 | |
| EP4268851A1 (en) | Composition for preventing or treating cancer, containing lipid nanoparticles | |
| EP4540392A1 (en) | Targeted nanomedicine for treating fibrotic lung disorders | |
| Huang | Functionalized Lipid Nanoparticles Show Efficacy in Glioma Animal Models | |
| CN104248768A (zh) | 靶向中枢神经系统的纳米药物载体 |