CN109077994A - Micro-molecular hydrogel-nanoparticle combination drug carrier and its application in skin/mucoadhesive delivery system - Google Patents
Micro-molecular hydrogel-nanoparticle combination drug carrier and its application in skin/mucoadhesive delivery system Download PDFInfo
- Publication number
- CN109077994A CN109077994A CN201811025663.3A CN201811025663A CN109077994A CN 109077994 A CN109077994 A CN 109077994A CN 201811025663 A CN201811025663 A CN 201811025663A CN 109077994 A CN109077994 A CN 109077994A
- Authority
- CN
- China
- Prior art keywords
- carrier
- micro
- drug
- molecular hydrogel
- nanoparticle
- 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.)
- Granted
Links
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 30
- 229940000425 combination drug Drugs 0.000 title claims abstract description 23
- 239000003937 drug carrier Substances 0.000 title claims abstract description 23
- 230000003232 mucoadhesive effect Effects 0.000 title claims abstract description 5
- 239000003814 drug Substances 0.000 claims abstract description 51
- 229940079593 drug Drugs 0.000 claims abstract description 36
- 239000000017 hydrogel Substances 0.000 claims abstract description 31
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 claims abstract description 26
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 claims abstract description 26
- 230000004048 modification Effects 0.000 claims abstract description 12
- 238000012986 modification Methods 0.000 claims abstract description 12
- 239000002245 particle Substances 0.000 claims abstract description 12
- 150000002632 lipids Chemical class 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- 239000002502 liposome Substances 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 239000000499 gel Substances 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 229930012538 Paclitaxel Natural products 0.000 claims description 6
- 229960001592 paclitaxel Drugs 0.000 claims description 6
- 239000002243 precursor Substances 0.000 claims description 6
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 6
- 102000004190 Enzymes Human genes 0.000 claims description 5
- 108090000790 Enzymes Proteins 0.000 claims description 5
- VBVAVBCYMYWNOU-UHFFFAOYSA-N coumarin 6 Chemical compound C1=CC=C2SC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 VBVAVBCYMYWNOU-UHFFFAOYSA-N 0.000 claims description 5
- 239000012153 distilled water Substances 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 4
- -1 micella Polymers 0.000 claims description 4
- 229920000642 polymer Polymers 0.000 claims description 4
- 239000006185 dispersion Substances 0.000 claims description 3
- 239000012467 final product Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 229920000136 polysorbate Polymers 0.000 claims description 3
- 238000002390 rotary evaporation Methods 0.000 claims description 3
- 229940126586 small molecule drug Drugs 0.000 claims description 3
- 150000003384 small molecules Chemical class 0.000 claims description 3
- 238000002604 ultrasonography Methods 0.000 claims description 3
- 229960000074 biopharmaceutical Drugs 0.000 claims description 2
- 239000000412 dendrimer Substances 0.000 claims description 2
- 229920000736 dendritic polymer Polymers 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 230000036571 hydration Effects 0.000 claims description 2
- 238000006703 hydration reaction Methods 0.000 claims description 2
- 239000004530 micro-emulsion Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000007908 nanoemulsion Substances 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- 229920000724 poly(L-arginine) polymer Polymers 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 239000003292 glue Substances 0.000 claims 2
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 claims 1
- 229960004502 levodopa Drugs 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 210000004877 mucosa Anatomy 0.000 abstract description 7
- 230000003902 lesion Effects 0.000 abstract description 5
- 230000035699 permeability Effects 0.000 abstract description 5
- 210000004400 mucous membrane Anatomy 0.000 abstract description 4
- 238000001338 self-assembly Methods 0.000 description 8
- 238000009826 distribution Methods 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 5
- 238000009792 diffusion process Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- MMCLXNVHNGMAOE-BVYSQLATSA-N ON([C@@H](CC1=CC=CC=C1)C(=O)O)O.N[C@@H](CC1=CC=CC=C1)C(=O)O.N[C@@H](CC1=CC=CC=C1)C(=O)O Chemical compound ON([C@@H](CC1=CC=CC=C1)C(=O)O)O.N[C@@H](CC1=CC=CC=C1)C(=O)O.N[C@@H](CC1=CC=CC=C1)C(=O)O MMCLXNVHNGMAOE-BVYSQLATSA-N 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 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 description 2
- 239000000470 constituent Substances 0.000 description 2
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 230000005684 electric field Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 230000000149 penetrating effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- AXMZZGKKZDJGAZ-UHFFFAOYSA-N 4-(4-methylphenyl)-3-(4-methylsulfonylphenyl)-1-propyl-2h-pyrrol-5-one Chemical compound O=C1N(CCC)CC(C=2C=CC(=CC=2)S(C)(=O)=O)=C1C1=CC=C(C)C=C1 AXMZZGKKZDJGAZ-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000193755 Bacillus cereus Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920000832 Cutin Polymers 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 208000001126 Keratosis Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 229940075612 bacillus cereus Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000002041 carbon nanotube Substances 0.000 description 1
- 229910021393 carbon nanotube Inorganic materials 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229940109262 curcumin Drugs 0.000 description 1
- 235000012754 curcumin Nutrition 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 229960000593 imrecoxib Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000002539 nanocarrier Substances 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 239000012744 reinforcing agent Substances 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229940043263 traditional drug Drugs 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 230000032895 transmembrane transport Effects 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Dermatology (AREA)
- Biophysics (AREA)
- Dispersion Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of micro-molecular hydrogel-nanoparticle combination drug carrier and its applications in skin/mucoadhesive delivery system, the micro-molecular hydrogel-nanoparticle combination drug carrier includes drug-carrying nanometer particle and micro-molecular hydrogel, drug-carrying nanometer particle is dispersed in micro-molecular hydrogel, has cell-penetrating peptide in drug-carrying nanometer particle surface modification.Micro-molecular hydrogel of the invention-nanoparticle complex carrier is used for skin/mucosa delivery, by in nanoparticle surface modification cell-penetrating peptide, skin/mucous membrane of drug and the permeability of lesions position can be significantly improved, the problem of micro-molecular hydrogel solves solution dosage administration, and drug is easy to run off.
Description
Technical field
The invention belongs to technical field of medicine, and in particular to a kind of micro-molecular hydrogel-nanoparticle combination drug load
Body and its application in skin/mucoadhesive delivery system.
Background technique
Skin/mucosa delivery refers to mucous membrane (such as oral cavity, nasal cavity, lung) conduct by human skin or each cavity
Agents area.This kind of administration mode can to avoid gastrointestinal tract to the destruction of drug, avoid drug to the irritation of gastrointestinal tract, and phase
Compared with intravenously administrable, directly in the skin of lesion/mucosal sites administration, drug can be made to reach lesions position rapidly, significantly improved
The drug concentration of lesions position reduces the distribution of non-target tissue.It therefore is a kind of simple, quick and patient's friendly administration way
Diameter.But there is also challenges for skin/mucosa delivery mode: drug percutaneous skin or mucomembranous surface absorb, and are intended to pass through cell
Lipid membrane hydrophobic region, hydrophobic structure is penetrated to drug with restriction effect, and skin outermost layer is fine and close cuticula, by force
Hydrophobic structure causes bigger barrier to penetrating for drug.
Drug penetrates the Passive diffusion of biomembrane, and fat-soluble with drug has substantial connection, generally uses oil/water distribution coefficient
The fat-soluble of drug is measured, oil/water distribution coefficient is big, then and it is fat-soluble big, be conducive to drug transmembrane transport.The Passive intake of drug
Rate is related with the diffusion coefficient of drug, and the big drug of molecular weight, diffusional resistance is big, and diffusion rate is slow, it is difficult to penetrate skin,
Alveolar surface biomembrane, nasal membrane etc..There should be biggish grease distribution system advantageously by skin/mucosa delivery drug
Number, molecular weight is no more than 1000, therefore type is limited.
By taking some means to improve drug permeability, the type of transdermal delivery drug can be expanded.Currently, improving medicine
The method of the transdermal efficiency of object has very much, is broadly divided into active and two kinds of passive-type, and passive-type method, which refers to, utilizes chemosmosis
Reinforcing agent, biological peptide and pharmaceutical preparation carrier, such as: lipid nano particle (liposome), metallic nanoparticle, polymer nanoparticle
Deng；Active method is then to interfere or destroy the barrier of skin by physical method, as micropin, microwave, electro-ionic osmosis, electricity are worn
Hole, Ultrasonic penetration, magnetic conductance enter, laser etc..
But it is mentioned using pharmaceutical preparation carriers such as lipid nano particle (liposome), metallic nanoparticle, polymer nanoparticles
The generally existing preparation of the method for high drug permeability is in the skin/mucosa delivery position residence time is short, needs the problem of frequent drug administration.
Summary of the invention
The object of the present invention is to provide a kind of micro-molecular hydrogel-nanoparticle combination drug carrier and its in skin/mucous membrane
Application in drug delivery system.
Micro-molecular hydrogel-nanoparticle combination drug carrier, including drug-carrying nanometer particle and micro-molecular hydrogel, medicament-carried nano
Grain is dispersed in micro-molecular hydrogel；There is cell-penetrating peptide in drug-carrying nanometer particle surface modification.
Further, the drug-carrying nanometer particle be selected from liposome, carrier, solid lipid nano granule, nano-emulsion, micro emulsion,
Vesica, dendrimers, micella, polymer nanoparticle or inorganic nano-particle, such as carbon nanotube, gold nano grain, quantum dot.
Further, the drug of drug-carrying nanometer particle institute load is selected from small-molecule drug, such as adriamycin, taxol, sea
Nurse moors sweet smell, imrecoxib, Wei Luofeini etc.；Or biopharmaceutical macromolecular drug, such as polypeptide, albumen, enzyme, hormone, vaccine, cell growth
The factor, monoclonal antibody, glycan and nucleic acid.
Further, the cell-penetrating peptide is selected from TD (ACSSSPSKHCG), TAT (GRKKRRQRRRPQ), T2
(LVGVFH), 11R (RRRRRRRRRRR), R8H3 (RRRRRRRRHHH) etc..
Further, gelator of the micro-molecular hydrogel by molecular weight lower than 2000 has under non-covalent bond effect
Sequence arrangement self-assemble is formed.By changing pH, temperature, electric field, magnetic field, ionic strength, chemical substance, introducing light or enzyme being added
The system of can star is self-assembly of micro-molecular hydrogel.
Above-mentioned micro-molecular hydrogel-application of the nanoparticle combination drug carrier in skin/mucoadhesive delivery system.
A kind of micro-molecular hydrogel-carrier combination drug carrier, is made of load medicine carrier and micro-molecular hydrogel, carries
Medicine carrier is dispersed in micro-molecular hydrogel；
The load medicine carrier is made of phosphatide, NaTDC, tween, and load taxol or coumarin 6, is carrying
Medicine carrier surface modification has cell-penetrating peptide, which is eight poly arginines, three polyhistidyl of Stearate Modified
(Stearylated-octaarginine-trihistidine, Ste-RRRRRRRRHHH, Ste-R8H3)；
The micro-molecular hydrogel is by gel precursors fluorenylmethyloxycarbonyl-phenylalanine and phenylalanine-phenylalanine-dihydroxy
Phenylalanine is made.
Above-mentioned micro-molecular hydrogel-carrier combination drug carrier preparation method, comprising the following steps:
Step 1, carrier is prepared by film dispersion method: soybean lecithin, surfactant and fat-soluble medicine is molten
In organic solvent, rotary evaporation in vacuo removes organic solvent, and distilled water hydration is added, filters after ultrasound, obtains carrier；
Step 2, medicine carrier surface modification cell-penetrating peptide is being carried: altogether in 4 DEG C by carrier and cell-penetrating peptide solution
Incubate 40min to obtain the final product；
Step 3, micro-molecular hydrogel-carrier combination drug carrier preparation: gel precursors are dissolved in distilled water, are adjusted
Save pH to 7.4, carrier be added, enzyme solution is then added, be placed in after mixing 37 DEG C of incubators reaction 4h to get.
Carrier: it is also known as elastic liposomes (flexible nano-liposomes), 1992, carrier was for the first time retouched by Cevc team
It states as a kind of liposome for cutaneous penetration, deformation behavior and elasticity are more preferable compared with traditional liposomal.Carrier is a kind of
The artificial carrier being made of phosphatide and surfactant, surfactant be also referred to as edge activator (edge activators,
EA the form of carrier) is determined.The transdermal mechanism of carrier: carrier self can polymerize, and can transmit drugs through skin
After resile, than traditional liposomal, that elasticity is good is very much, this high deformation behavior allow carrier by deformation pass through than from
The hole that small 5-10 times of body partial size, therefore be a kind of new transdermal drug transmission carrier.Drug transdermal transmission is improved at this stage
Mechanism is also indefinite, there are two types of mechanism it has been reported that: 1) carrier is used as pharmaceutical carrier, is able to maintain after skin completely
Form；2) carrier is as penetration-assisting agent, the intercellular lipid for interfering cutin layer height orderly, thus promote Medicated Permeation and
Across cuticula.
Micro-molecular hydrogel is crosslinked and is wound by being self-assembly of oversubscription subchain and then every chain between small molecule
Hydrone is wrapped in intermediate three-dimensional net structure.Can be substantially divided by starting the method for being self-assembly of hydrogel by two kinds:
One is self assembly is started by the adjusting to system environment, such as change pH, temperature, electric field, magnetic field, ionic strength, chemicals
Matter etc.；It is another then be to carry out stimulation to the precursor that not can be carried out self assembly and formed to be able to carry out the gel primitive of self assembly, such as
Light or enzymatic.Micro-molecular hydrogel can be used as the new biomaterial of one kind and be applied to organizational project, cell culture substrate,
Drug delivery etc..Moreover, the tridimensional network being self-assembly of can wrap up hydrone, other biological activities molecule (nutrition
Substance and albumen) and drug, it can be used as medicine sustained and controlled release carrier.
Cell-penetrating peptide (Cell penetrating peptides, CPP) is i.e. with the small peptide of penetrating cell film ability.
It finds for the first time within 1988, the HIV trans-activating factor Tat (GRKKRRQRRRPQ) of transcription factor, which has, passes through plasma membrane, into thin
The ability of born of the same parents.Cell-penetrating peptide is transmitted exogenous small peptide by first time in 1994, occurs from there on a variety of different
Cell-penetrating peptide, these cell-penetrating peptides can successfully transmit albumen, nucleic acid, small-molecule drug, antibody, nano-carrier etc..Santanu
Oligomerization arginine is connected to the liposome that cell-penetrating peptide modification is synthesized on cholesterol by Patra etc., and in vivo and experiment in vitro all shows
The modification of cell-penetrating peptide can significantly improve the percutaneous permeability of curcumin, it was demonstrated that cell-penetrating peptide is played the part of in Cutaneous permeation and transdermal release
Drill important role.
Micro-molecular hydrogel of the invention-nanoparticle complex carrier is used for skin/mucosa delivery, by nanoparticle surface
Cell-penetrating peptide is modified, skin/mucous membrane of drug and the permeability of lesions position can be significantly improved, micro-molecular hydrogel solves molten
The problem of liquor type administration, drug is easy to run off.
Detailed description of the invention
Fig. 1 is 1 small molecular hydrogel of embodiment-carrier combination drug carrier preparation principle figure；
Fig. 2 is the grain size distribution that cell-penetrating peptide modifies carrier in embodiment 1；
Fig. 3 is that the accumulative skin permeation rate of vitro Drug of carrier in embodiment 1, cell-penetrating peptide modification carrier and liposome compares
As a result；
Fig. 4 is 1 small molecular hydrogel of embodiment-carrier combination drug carrier freeze-drying sample SEM figure, schemes the mark of a
Ruler is 100 μm, and the scale for scheming b is 1 μm；
Fig. 5 is that 1 small molecular hydrogel of embodiment-carrier combination drug carrier vitro Drug adds up skin permeation rate knot
Fruit.
Specific embodiment
Embodiment 1
The preparation of blank carrier: carrier is prepared by film dispersion method, by phosphatide (SPC), NaTDC and table
Face active constituent (edge activator, EA) is dissolved in chloroform according to the proportion of table 1: in methanol=2:1 organic solvent, at 40 DEG C
At a temperature of rotary evaporation in vacuo method remove organic solvent, lipid components form adipose membrane in bottle wall, are subsequently placed in vacuum drying kettle
Residual organic solvent is removed overnight.DdH is added2O is hydrated 10min, uses sonde-type cell Ultrasonic Cell Disruptor ice-bath ultrasonic 5min
Disperse lipid suspension, the Liposomal suspensions that ultrasound is crossed, which are crossed 0.22 μm of cellulose ester membrane, can be obtained the carrier of uniform particle diameter
(Ts).Traditional liposomal (Ls) is prepared simultaneously as control.
Carry medicine carrier preparation: carry taxol (PTX) or coumarin 6 (Cou6) carrier preparation only need to by PTX (or
Cou6 it) is dissolved in organic solvent together with lipid components and preparing according to the above method, wherein PTX loading is to account for lipid components
The 3.3% of gross mass, coumarin 6 account for the 0.2% of lipid components gross mass.Prepare traditional drug-loaded liposome (Ls) simultaneously.
The constituent of 1 different liposome of table
The carrier preparation of cell-penetrating peptide modification: it is added lipid total amount 2.5mol%'s in the carrier that the above method is obtained
Cell-penetrating peptide solution is incubated for 40 minutes at 4 DEG C to obtain the final product；
The carrier partial size of the cell-penetrating peptide modification of load taxol measures result such as Fig. 2 institute using dynamic light scattering method
Show, the results showed that particle diameter distribution is distributed in 75nm or so, and partial size is in normal distribution, is distributed uniform.
In vitro transdermal test: investigating the transdermal capability of Cou6-CTs using transdermal diffusion apparatus, and 6-7 weeks male nude mouse is put to death
After cut off skin of abdomen, removed with scissors and remove the fat deposit and connective tissue that stick with isopropanol after subcutaneous tissue, paid attention to
Skin is not damaged during this, is finally cleaned with 0.9%NaCl spare.Setting speed of agitator is 500rpm, by what is handled well
Skin is fixed on Franz diffusion cell, and keratoderma connects towards administration pond, skin inner layer with the buffer in sample acceptance pool
Touching, buffer is by ethyl alcohol: PBS=1:3 is formed, and is used after ultrasonic bubble removing is handled.Different 300 μ L of liposomal samples is uniform
Administration pond is added that area is administered to be 3.14cm2, 800 μ are sampled from sample acceptance pool when 0.5,1,2,4,6,8,12h
L feeds the buffer of same volume after every sub-sampling.Drug accumulation transmitance calculates as follows:
A is dosage, and V is receiving liquid volume, and Cn is that n-th samples sample concentration, when Ci is i-th sampling in receiving liquid
The concentration of sample, Vi are sample volume.
Accumulative release rate calculated result is as shown in Figure 3: transdermal carrier as the result is shown (Ts, CTs) is compared to traditional liposomal
Body (Ls) has good transdermal effect, and the transdermal efficiency of carrier is significantly improved after addition CPP, compared to traditional lipid
The transdermal efficiency of carrier CTs of body, this experimental design improves nearly 4 times.
The preparation of micro-molecular hydrogel-carrier complex carrier: a certain amount of 10mM fluorenylmethyloxycarbonyl-phenylalanine is taken
(Fmoc-F) and 20mM phenylalanine-phenylalanine-dihydroxyphenylalanine (F-F-DOPA) is used as gel precursors, is completely dissolved in
It by pH to 7.4 or so after in distilled water, is mixed with 250 μ L carriers (CTs), 200 μ L WQ9-2 enzyme solution (1mg/ is then added
ML, bacterial strain Bacilluscereus WQ9-2 (CN102021125A), the white WQ9-2 that lays eggs, which have, catalyzes and synthesizes hydrogelator
Performance), be uniformly mixed and be placed in 37 DEG C of incubators, react 4h.
Fig. 4 is that sample SEM figure, the SEM after sample vacuum freeze drying is lyophilized in micro-molecular hydrogel-carrier complex carrier
It can be used for observing after gelator winds aggregation by way of self assembly and be formed by tridimensional network.It can from figure a
To see that the three-dimensional framework of hydrogel is cross-linked to form porous structure by dendritic structure.About 10-30 μm of skeleton size, in this way
Porous stent structure on the one hand provide skeletal support for gel and on the other hand can scheme b partial enlargement (i.e. figure b) with load drug
It can be seen that carrier is loaded in gel voids structure and the size of carrier is 100nm or so.
Micro-molecular hydrogel-carrier in vitro transdermal test: operating method adds up release with carrier in vitro transdermal test
Rate calculated result is as shown in Figure 5: the transdermal result of micro-molecular hydrogel-carrier 12h is about 12%, shows micro-molecular hydrogel
The skin penetration rate of carrier may be slowed down as storage cavern.
Claims (8)
1. micro-molecular hydrogel-nanoparticle combination drug carrier, it is characterised in that: including drug-carrying nanometer particle and small molecule water-setting
Glue, drug-carrying nanometer particle are dispersed in micro-molecular hydrogel；There is cell-penetrating peptide in drug-carrying nanometer particle surface modification.
2. micro-molecular hydrogel according to claim 1-nanoparticle combination drug carrier, it is characterised in that: the load medicine
Nanoparticle is selected from liposome, solid lipid nano granule, nano-emulsion, micro emulsion, vesica, dendrimers, micella, polymer nanoparticle
Or inorganic nano-particle.
3. micro-molecular hydrogel according to claim 1-nanoparticle combination drug carrier, it is characterised in that: the load medicine
The drug of nanoparticle institute load is selected from small-molecule drug or biopharmaceutical macromolecular drug.
4. micro-molecular hydrogel according to claim 1-nanoparticle combination drug carrier, it is characterised in that: the cell
Cell-penetrating peptide is selected from TD, TAT, T2,11R or R8H3.
5. micro-molecular hydrogel according to claim 1-nanoparticle combination drug carrier, it is characterised in that: described small point
Gelator of the sub- hydrogel by molecular weight lower than 2000 ordered arrangement self-assemble under non-covalent bond effect is formed.
6. micro-molecular hydrogel described in claim 1-nanoparticle combination drug carrier answering in skin/mucoadhesive delivery system
With.
7. a kind of micro-molecular hydrogel-carrier combination drug carrier, it is characterised in that: by load medicine carrier and small molecule water-setting
Glue composition carries medicine carrier and is dispersed in micro-molecular hydrogel；
The load medicine carrier is made of phosphatide, NaTDC, tween, and load taxol or coumarin 6, passes carrying medicine
It passs body surface face and is modified with cell-penetrating peptide, which is eight poly arginines, three polyhistidyl of Stearate Modified；
The micro-molecular hydrogel is by gel precursors fluorenylmethyloxycarbonyl-phenylalanine and phenylalanine-phenylalanine-dihydroxyphenyl third
Propylhomoserin is made.
8. micro-molecular hydrogel according to claim 7-carrier combination drug carrier preparation method, feature exist
In: the following steps are included:
Step 1, carrier is prepared by film dispersion method: phosphatide, NaTDC, tween, taxol/coumarin 6 is dissolved in
In organic solvent, rotary evaporation in vacuo removes organic solvent, and distilled water hydration is added, filters after ultrasound, obtains carrier；
Step 2, there is cell-penetrating peptide in load medicine carrier surface modification: carrier is incubated with cell-penetrating peptide solution in 4 DEG C altogether
40 min to obtain the final product；
Step 3, micro-molecular hydrogel-carrier combination drug carrier preparation: by gel precursors fluorenylmethyloxycarbonyl-phenylalanine
It is dissolved in distilled water with alanine-phenylalanine-dihydroxyphenylalanine, adjusts pH to 7.4, carrier is added, enzyme is then added
Liquid, be placed in after mixing 37 DEG C of incubators react 4 h to get.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811025663.3A CN109077994B (en) | 2018-09-04 | 2018-09-04 | Small molecular hydrogel-nanoparticle composite drug carrier and application thereof in skin/mucosa drug delivery system |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811025663.3A CN109077994B (en) | 2018-09-04 | 2018-09-04 | Small molecular hydrogel-nanoparticle composite drug carrier and application thereof in skin/mucosa drug delivery system |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109077994A true CN109077994A (en) | 2018-12-25 |
| CN109077994B CN109077994B (en) | 2021-11-30 |
Family
ID=64840858
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811025663.3A Active CN109077994B (en) | 2018-09-04 | 2018-09-04 | Small molecular hydrogel-nanoparticle composite drug carrier and application thereof in skin/mucosa drug delivery system |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109077994B (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109998994A (en) * | 2018-02-13 | 2019-07-12 | 四川大学 | Flexible lipidosome and preparation method thereof comprising drug |
| CN111568855A (en) * | 2020-06-08 | 2020-08-25 | 山东大学 | Preparation method of injectable hydrogel and application of injectable hydrogel in postoperative tumor treatment |
| CN111686075A (en) * | 2019-03-15 | 2020-09-22 | 四川大学 | In-situ hydrogel composition taking nano-micelle as cross-linking agent and application thereof |
| CN113559054A (en) * | 2021-05-14 | 2021-10-29 | 南京工业大学 | Active oxygen scavenging/responding allosteric self-assembly hydrogel and application thereof |
| CN113908138A (en) * | 2021-09-08 | 2022-01-11 | 四川大学华西医院 | Glioma antibody pharmaceutical composition and preparation method thereof |
| CN114107397A (en) * | 2021-11-19 | 2022-03-01 | 深圳市大鳄生物科技股份有限公司 | Delivery system, complex and drug for delivering negatively charged nucleic acids |
| CN114948852A (en) * | 2022-05-26 | 2022-08-30 | 深圳先进技术研究院 | Microneedle system for diagnosis and treatment of brain diseases and preparation method thereof |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101711874A (en) * | 2008-10-08 | 2010-05-26 | 广州暨南大学医药生物技术研究开发中心 | Application of cell penetrating peptide Tat-mediated growth factor in transdermal transfer |
| CN102091036A (en) * | 2011-01-10 | 2011-06-15 | 中国药科大学 | Compound liposome containing anti-tumor drugs and preparation method and application thereof |
| CN102174078A (en) * | 2011-01-10 | 2011-09-07 | 中国药科大学 | Application of tumor cell membrane selectively penetrating peptide |
| CN102406609A (en) * | 2011-12-01 | 2012-04-11 | 天津医科大学口腔医院 | Lidocaine hydrochloride polymeric liposome for topical anesthesia and preparation method |
| CN102743338A (en) * | 2012-05-09 | 2012-10-24 | 中国药科大学 | Oral composite nano-carrier based on cell-permeable peptide, preparation method and use thereof |
| CN103655455A (en) * | 2012-09-11 | 2014-03-26 | 上海交通大学医学院附属第九人民医院 | Nanoscale carrier loading 5-fluorouracil gel and preparation method thereof |
| CN105310983A (en) * | 2014-08-03 | 2016-02-10 | 孙仁 | Rupturable PEG modified adriamycin liposome preparation method |
| CN106177986A (en) * | 2016-08-16 | 2016-12-07 | 国家纳米科学中心 | A kind of lipopolymer medicine-carried nano particles and its preparation method and application |
| CN107088184A (en) * | 2017-04-21 | 2017-08-25 | 南京工业大学 | Orient Enzymatic reac tion system and its application in micro-molecular hydrogel is prepared |
| KR101813560B1 (en) * | 2016-06-24 | 2018-01-31 | 주식회사 바이오에프디엔씨 | Topical formulation with Skin Physiological Activity Composed of Cell Permeable Growth Factors |
| CN107815470A (en) * | 2017-10-11 | 2018-03-20 | 江苏大学 | A kind of preparation method of the compound gene activation support of liposome/gel |
| CN107998070A (en) * | 2017-12-12 | 2018-05-08 | 南京中医药大学 | A kind of composite phospholipid carrier and its application in percutaneous drug administration preparation is prepared |
-
2018
- 2018-09-04 CN CN201811025663.3A patent/CN109077994B/en active Active
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101711874A (en) * | 2008-10-08 | 2010-05-26 | 广州暨南大学医药生物技术研究开发中心 | Application of cell penetrating peptide Tat-mediated growth factor in transdermal transfer |
| CN102091036A (en) * | 2011-01-10 | 2011-06-15 | 中国药科大学 | Compound liposome containing anti-tumor drugs and preparation method and application thereof |
| CN102174078A (en) * | 2011-01-10 | 2011-09-07 | 中国药科大学 | Application of tumor cell membrane selectively penetrating peptide |
| CN102406609A (en) * | 2011-12-01 | 2012-04-11 | 天津医科大学口腔医院 | Lidocaine hydrochloride polymeric liposome for topical anesthesia and preparation method |
| CN102743338A (en) * | 2012-05-09 | 2012-10-24 | 中国药科大学 | Oral composite nano-carrier based on cell-permeable peptide, preparation method and use thereof |
| CN103655455A (en) * | 2012-09-11 | 2014-03-26 | 上海交通大学医学院附属第九人民医院 | Nanoscale carrier loading 5-fluorouracil gel and preparation method thereof |
| CN105310983A (en) * | 2014-08-03 | 2016-02-10 | 孙仁 | Rupturable PEG modified adriamycin liposome preparation method |
| KR101813560B1 (en) * | 2016-06-24 | 2018-01-31 | 주식회사 바이오에프디엔씨 | Topical formulation with Skin Physiological Activity Composed of Cell Permeable Growth Factors |
| CN106177986A (en) * | 2016-08-16 | 2016-12-07 | 国家纳米科学中心 | A kind of lipopolymer medicine-carried nano particles and its preparation method and application |
| CN107088184A (en) * | 2017-04-21 | 2017-08-25 | 南京工业大学 | Orient Enzymatic reac tion system and its application in micro-molecular hydrogel is prepared |
| CN107815470A (en) * | 2017-10-11 | 2018-03-20 | 江苏大学 | A kind of preparation method of the compound gene activation support of liposome/gel |
| CN107998070A (en) * | 2017-12-12 | 2018-05-08 | 南京中医药大学 | A kind of composite phospholipid carrier and its application in percutaneous drug administration preparation is prepared |
Non-Patent Citations (5)
| Title |
|---|
| J. X. XU等: "Enzymatic formation of a novel cell-adhesive hydrogel based on small peptides with a laterally grafted L-3,4-dihydroxyphenylalanine group", 《NANOSCALE》 * |
| TIANYUE JIANG等: "Enhanced Transdermal Drug Delivery by Transfersome-Embedded Oligopeptide Hydrogel for Topical Chemotherapy of Melanoma", 《ACS NANO》 * |
| TIANYUE JIANG等: "Gel–Liposome-Mediated Co-Delivery of Anticancer Membrane-Associated Proteins and Small-Molecule Drugs for Enhanced Therapeutic Efficacy", 《ADVANCED FUNCTIONAL MATERIALS》 * |
| 吴青青: "姜黄素脂质体和脂质体凝胶的制备及其经皮给药研究", 《万方学位论文》 * |
| 杨秀丽等: "紫杉醇纳米脂质体凝胶剂的制备及体外透皮研究", 《中国现代应用药学》 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109998994A (en) * | 2018-02-13 | 2019-07-12 | 四川大学 | Flexible lipidosome and preparation method thereof comprising drug |
| CN109998994B (en) * | 2018-02-13 | 2021-12-07 | 四川大学 | Flexible liposome containing medicine and preparation method thereof |
| CN111686075A (en) * | 2019-03-15 | 2020-09-22 | 四川大学 | In-situ hydrogel composition taking nano-micelle as cross-linking agent and application thereof |
| CN111686075B (en) * | 2019-03-15 | 2021-09-17 | 四川大学 | In-situ hydrogel composition taking nano-micelle as cross-linking agent and application thereof |
| CN111568855A (en) * | 2020-06-08 | 2020-08-25 | 山东大学 | Preparation method of injectable hydrogel and application of injectable hydrogel in postoperative tumor treatment |
| CN111568855B (en) * | 2020-06-08 | 2022-02-08 | 山东大学 | Preparation method of injectable hydrogel and application of injectable hydrogel in postoperative tumor treatment |
| CN113559054A (en) * | 2021-05-14 | 2021-10-29 | 南京工业大学 | Active oxygen scavenging/responding allosteric self-assembly hydrogel and application thereof |
| CN113908138A (en) * | 2021-09-08 | 2022-01-11 | 四川大学华西医院 | Glioma antibody pharmaceutical composition and preparation method thereof |
| CN114107397A (en) * | 2021-11-19 | 2022-03-01 | 深圳市大鳄生物科技股份有限公司 | Delivery system, complex and drug for delivering negatively charged nucleic acids |
| CN114948852A (en) * | 2022-05-26 | 2022-08-30 | 深圳先进技术研究院 | Microneedle system for diagnosis and treatment of brain diseases and preparation method thereof |
| CN114948852B (en) * | 2022-05-26 | 2024-05-17 | 深圳先进技术研究院 | Microneedle system for brain disease diagnosis and treatment and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109077994B (en) | 2021-11-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109077994A (en) | Micro-molecular hydrogel-nanoparticle combination drug carrier and its application in skin/mucoadhesive delivery system | |
| Dymek et al. | Liposomes as biocompatible and smart delivery systems–the current state | |
| Yan et al. | A pH-responsive drug-delivery platform based on glycol chitosan–coated liposomes | |
| US8715736B2 (en) | Nanoparticle formulations for skin delivery | |
| Ariga et al. | Layer-by-layer self-assembled shells for drug delivery | |
| JP5405527B2 (en) | Novel preparation of pharmacological drug, its production method and use | |
| EP2288336B1 (en) | Nanostructures suitable for sequestering cholesterol | |
| US9066885B2 (en) | Advanced functional biocompatible polymeric matrix containing nano-compartments | |
| JPH08509230A (en) | Cyclodextrin liposome encapsulating pharmaceutical compound and use thereof | |
| CN104415338B (en) | Active targeting type antineoplastic and preparation method thereof | |
| WO2020103832A1 (en) | Method for preparing flexible lipidosome | |
| Chaudhary | Aquasomes; A new approach for delivering therapeutics: an overview | |
| CN107638388B (en) | Asiatic acid chitosan deoxycholic acid graft micelle and preparation method thereof | |
| CN101953792A (en) | Irinotecan nano circulating liposome and preparation method thereof | |
| CN105722530A (en) | Designed peptides for tight junction barrier modulation | |
| Gupta et al. | Bilosomes: a novel platform for drug delivery | |
| Ye et al. | Functionalized multiwalled carbon nanotube-ethosomes for transdermal delivery of ketoprofen: Ex vivo and in vivo evaluation | |
| CN103990136B (en) | Transdermal drug delivery system, preparation method and application thereof | |
| Sallam et al. | Colloidal delivery of drugs: present strategies and conditions | |
| CN113368257A (en) | Preparation method of nanoparticle composition delivery system | |
| CN102188379A (en) | Preparation method of drug-carrying liposome | |
| CN110759974B (en) | Phospholipid-polyethylene glycol-rabies virus derived peptide polymer, and preparation method and application thereof | |
| Charumathy et al. | Recent update on liposome-based drug delivery system | |
| Wang et al. | Preparation and properties of semi-self-assembled lipopeptide vesicles | |
| CN102091332B (en) | Self-assembly system based on hydrophilic polymer and medicine and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |