CA2304134A1 - Liberation de medicament localisee, activee par voie acoustique - Google Patents
Liberation de medicament localisee, activee par voie acoustique Download PDFInfo
- Publication number
- CA2304134A1 CA2304134A1 CA002304134A CA2304134A CA2304134A1 CA 2304134 A1 CA2304134 A1 CA 2304134A1 CA 002304134 A CA002304134 A CA 002304134A CA 2304134 A CA2304134 A CA 2304134A CA 2304134 A1 CA2304134 A1 CA 2304134A1
- Authority
- CA
- Canada
- Prior art keywords
- drug
- cells
- doxorubicin
- poly
- micelles
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000012377 drug delivery Methods 0.000 title description 17
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims abstract description 244
- 239000003814 drug Substances 0.000 claims abstract description 181
- 229940079593 drug Drugs 0.000 claims abstract description 179
- 229960004679 doxorubicin Drugs 0.000 claims abstract description 120
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 53
- 238000000034 method Methods 0.000 claims abstract description 45
- 239000000203 mixture Substances 0.000 claims abstract description 24
- 239000003937 drug carrier Substances 0.000 claims abstract description 20
- 229920000428 triblock copolymer Polymers 0.000 claims abstract description 15
- 229920001400 block copolymer Polymers 0.000 claims abstract description 12
- 229920000463 Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) Polymers 0.000 claims abstract description 9
- GYPCWHHQAVLMKO-XXKQIVDLSA-N (7s,9s)-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-[(e)-n-[(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-ylidene)amino]-c-methylcarbonimidoyl]-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical group Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(\C)=N\N=C1CC(C)(C)N(O)C(C)(C)C1)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 GYPCWHHQAVLMKO-XXKQIVDLSA-N 0.000 claims description 60
- 230000000694 effects Effects 0.000 claims description 31
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 14
- -1 poly(ethylene oxide) Polymers 0.000 claims description 13
- 229940045799 anthracyclines and related substance Drugs 0.000 claims description 11
- 230000002708 enhancing effect Effects 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 abstract description 15
- 229940034982 antineoplastic agent Drugs 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 159
- 239000000693 micelle Substances 0.000 description 106
- 238000002604 ultrasonography Methods 0.000 description 62
- 239000000243 solution Substances 0.000 description 51
- 229920002065 Pluronic® P 105 Polymers 0.000 description 46
- 229920001983 poloxamer Polymers 0.000 description 31
- 238000009210 therapy by ultrasound Methods 0.000 description 24
- 206010028980 Neoplasm Diseases 0.000 description 22
- 108020004414 DNA Proteins 0.000 description 17
- 238000011282 treatment Methods 0.000 description 16
- 230000003834 intracellular effect Effects 0.000 description 15
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 14
- 230000001965 increasing effect Effects 0.000 description 14
- 230000014759 maintenance of location Effects 0.000 description 14
- 238000010791 quenching Methods 0.000 description 14
- 230000000171 quenching effect Effects 0.000 description 13
- 229920001577 copolymer Polymers 0.000 description 12
- 238000011534 incubation Methods 0.000 description 12
- 238000000527 sonication Methods 0.000 description 12
- 239000004094 surface-active agent Substances 0.000 description 12
- 238000002525 ultrasonication Methods 0.000 description 11
- 238000009825 accumulation Methods 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 229940041181 antineoplastic drug Drugs 0.000 description 9
- 229920001451 polypropylene glycol Polymers 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 201000004283 Shwachman-Diamond syndrome Diseases 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 210000000170 cell membrane Anatomy 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 238000005063 solubilization Methods 0.000 description 8
- 230000007928 solubilization Effects 0.000 description 8
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 7
- 238000004435 EPR spectroscopy Methods 0.000 description 7
- 239000004793 Polystyrene Substances 0.000 description 7
- 239000000084 colloidal system Substances 0.000 description 7
- 230000003013 cytotoxicity Effects 0.000 description 7
- 231100000135 cytotoxicity Toxicity 0.000 description 7
- 238000005538 encapsulation Methods 0.000 description 7
- 239000006166 lysate Substances 0.000 description 7
- 229920002223 polystyrene Polymers 0.000 description 7
- AGGKEGLBGGJEBZ-UHFFFAOYSA-N tetramethylenedisulfotetramine Chemical compound C1N(S2(=O)=O)CN3S(=O)(=O)N1CN2C3 AGGKEGLBGGJEBZ-UHFFFAOYSA-N 0.000 description 7
- 206010048723 Multiple-drug resistance Diseases 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 231100000433 cytotoxic Toxicity 0.000 description 6
- 230000001472 cytotoxic effect Effects 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 230000035699 permeability Effects 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 101001017818 Homo sapiens ATP-dependent translocase ABCB1 Proteins 0.000 description 5
- 239000013592 cell lysate Substances 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 206010013710 Drug interaction Diseases 0.000 description 4
- 239000012979 RPMI medium Substances 0.000 description 4
- 239000000562 conjugate Substances 0.000 description 4
- 229940127089 cytotoxic agent Drugs 0.000 description 4
- 238000001362 electron spin resonance spectrum Methods 0.000 description 4
- 238000009830 intercalation Methods 0.000 description 4
- 230000017095 negative regulation of cell growth Effects 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 238000004448 titration Methods 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- 206010059866 Drug resistance Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 231100000002 MTT assay Toxicity 0.000 description 3
- 238000000134 MTT assay Methods 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000006037 cell lysis Effects 0.000 description 3
- 238000002784 cytotoxicity assay Methods 0.000 description 3
- 231100000263 cytotoxicity test Toxicity 0.000 description 3
- 238000001506 fluorescence spectroscopy Methods 0.000 description 3
- 238000002189 fluorescence spectrum Methods 0.000 description 3
- 230000002687 intercalation Effects 0.000 description 3
- 239000004816 latex Substances 0.000 description 3
- 229920000126 latex Polymers 0.000 description 3
- 229920002521 macromolecule Polymers 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000005298 paramagnetic effect Effects 0.000 description 3
- 238000005192 partition Methods 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- RPAZYIOIDZRJOO-UHFFFAOYSA-N 16-DOXYL-stearic acid Chemical compound OC(=O)CCCCCCCCCCCCCCC1(CC)OCC(C)(C)N1[O] RPAZYIOIDZRJOO-UHFFFAOYSA-N 0.000 description 2
- 206010048610 Cardiotoxicity Diseases 0.000 description 2
- 206010015866 Extravasation Diseases 0.000 description 2
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 230000003698 anagen phase Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 231100000259 cardiotoxicity Toxicity 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000368 destabilizing effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 230000036251 extravasation Effects 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 230000007773 growth pattern Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 238000011533 pre-incubation Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- RZVHIXYEVGDQDX-UHFFFAOYSA-N 9,10-anthraquinone Chemical group C1=CC=C2C(=O)C3=CC=CC=C3C(=O)C2=C1 RZVHIXYEVGDQDX-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 241001082241 Lythrum hyssopifolia Species 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 206010006007 bone sarcoma Diseases 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 231100000457 cardiotoxic Toxicity 0.000 description 1
- 230000001451 cardiotoxic effect Effects 0.000 description 1
- 230000007681 cardiovascular toxicity Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 230000035567 cellular accumulation Effects 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000011258 core-shell material Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000007402 cytotoxic response Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009513 drug distribution Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 239000002563 ionic surfactant Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 210000000633 nuclear envelope Anatomy 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000014207 opsonization Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000010587 phase diagram Methods 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000580 polymer-drug conjugate Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000008261 resistance mechanism Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Biophysics (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Procédé de libération d'un médicament dans un site prédéterminé chez un patient, qui consiste (a) à administrer une composition contenant un vecteur de médicament micellaire ayant un noyau hydrophobe et une dose efficace du médicament placée dans ledit noyau; et (b) à appliquer de l'énergie ultrasonore sur le site sélectionné de sorte que le médicament soit libéré par le noyau hydrophobe sur le site sélectionné. Le vecteur de médicament est, de préférence, un copolymère tribloc, comme un copolymère bloc de poly(éthylène oxyde)-poly(propylène oxyde)-poly(éthylène oxyde) ayant un poids moléculaire d'environ 6500. Ledit médicament est de préférence un agent antinéoplasique comme la doxorubicine.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5977497P | 1997-09-23 | 1997-09-23 | |
| US60/059,774 | 1997-09-23 | ||
| PCT/US1998/020046 WO1999015151A1 (fr) | 1997-09-23 | 1998-09-23 | Liberation de medicament localisee, activee par voie acoustique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2304134A1 true CA2304134A1 (fr) | 1999-04-01 |
Family
ID=22025133
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002304134A Abandoned CA2304134A1 (fr) | 1997-09-23 | 1998-09-23 | Liberation de medicament localisee, activee par voie acoustique |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP1037608A1 (fr) |
| CA (1) | CA2304134A1 (fr) |
| WO (1) | WO1999015151A1 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12371522B2 (en) | 2011-10-12 | 2025-07-29 | The Johns Hopkins University | Bioreducible poly (beta-amino ester)s for siRNA delivery |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2458501A (en) * | 2000-01-05 | 2001-07-16 | Imarx Therapeutics, Inc. | Pharmaceutical formulations for the delivery of drugs having low aqueous solubility |
| EP2012804A4 (fr) * | 2006-04-24 | 2012-07-04 | Bruce Medical Ab | Agents anticancéreux à base de polymères |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5795581A (en) * | 1995-03-31 | 1998-08-18 | Sandia Corporation | Controlled release of molecular components of dendrimer/bioactive complexes |
-
1998
- 1998-09-23 CA CA002304134A patent/CA2304134A1/fr not_active Abandoned
- 1998-09-23 WO PCT/US1998/020046 patent/WO1999015151A1/fr not_active Ceased
- 1998-09-23 EP EP98950671A patent/EP1037608A1/fr not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12371522B2 (en) | 2011-10-12 | 2025-07-29 | The Johns Hopkins University | Bioreducible poly (beta-amino ester)s for siRNA delivery |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1037608A1 (fr) | 2000-09-27 |
| WO1999015151A1 (fr) | 1999-04-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Munshi et al. | Ultrasonic activated drug delivery from Pluronic P-105 micelles | |
| Xu et al. | Chemo-photodynamic therapy with light-triggered disassembly of theranostic nanoplatform in combination with checkpoint blockade for immunotherapy of hepatocellular carcinoma | |
| Rapoport et al. | Drug delivery in polymeric micelles: from in vitro to in vivo | |
| Houdaihed et al. | Overcoming the road blocks: advancement of block copolymer micelles for cancer therapy in the clinic | |
| Zhang et al. | Co-delivery of etoposide and cisplatin in dual-drug loaded nanoparticles synergistically improves chemoradiotherapy in non-small cell lung cancer models | |
| Liaw et al. | Dendrimer size effects on the selective brain tumor targeting in orthotopic tumor models upon systemic administration | |
| Kubo et al. | Targeted systemic chemotherapy using magnetic liposomes with incorporated adriamycin for osteosarcoma in hamsters. | |
| Liu et al. | Heat/pH-boosted release of 5-fluorouracil and albumin-bound paclitaxel from Cu-doped layered double hydroxide nanomedicine for synergistical chemo-photo-therapy of breast cancer | |
| Qian et al. | Combination of micelles and liposomes as a promising drug delivery system: a review | |
| Kubo et al. | Targeted delivery of anticancer drugs with intravenously administered magnetic liposomes in osteosarcoma-bearing hamsters. | |
| Ma et al. | Development of idarubicin and doxorubicin solid lipid nanoparticles to overcome Pgp-mediated multiple drug resistance in leukemia | |
| Kim et al. | Gemcitabine-loaded DSPE-PEG-PheoA liposome as a photomediated immune modulator for cholangiocarcinoma treatment | |
| Liu et al. | Effective co-encapsulation of doxorubicin and irinotecan for synergistic therapy using liposomes prepared with triethylammonium sucrose octasulfate as drug trapping agent | |
| Fraix et al. | Overcoming doxorubicin resistance with lipid–polymer hybrid nanoparticles photoreleasing nitric oxide | |
| Azzazy et al. | Peganum harmala alkaloids and tannic acid encapsulated in PAMAM dendrimers: improved anticancer activities as compared to doxorubicin | |
| Wen et al. | Dendritic polylysine with paclitaxel and triptolide codelivery for enhanced cancer ferroptosis through the accumulation of ROS | |
| Hani et al. | A comprehensive review of current perspectives on novel drug Delivery systems and approaches for lung cancer management | |
| Viard et al. | Design and biological activity of novel stealth polymeric lipid nanoparticles for enhanced delivery of hydrophobic photodynamic therapy drugs | |
| EP1221946A2 (fr) | Activation ciblee d'un medicament | |
| Xiao et al. | pH-/redox-responsive nanodroplet combined with ultrasound-targeted microbubble destruction for the targeted treatment of drug-resistant triple negative breast cancer | |
| CN106821987B (zh) | 一种载含酚羟基难溶性药物的脂质体及制备方法和应用 | |
| Saremi et al. | Development of a stable and high loaded liposomal formulation of lapatinib with enhanced therapeutic effects for breast cancer in combination with Caelyx®: in vitro and in vivo evaluations | |
| Wang et al. | Engineering metal-organic framework nanoparticles trigger pyroptosis to boost colon cancer immunotherapy | |
| US20050003008A1 (en) | Method of in vivo drug targeting to solid tumors via acoustically triggered drug delivery in polymeric micelles | |
| Jiao et al. | Intelligent porphyrin nano-delivery system for photostimulated and targeted inhibition of angiogenesis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |