CN1297318C - Prepn of core-shell type nano compound hydroxyapatiti-liposome particle - Google Patents

Prepn of core-shell type nano compound hydroxyapatiti-liposome particle Download PDF

Info

Publication number
CN1297318C
CN1297318C CNB021111316A CN02111131A CN1297318C CN 1297318 C CN1297318 C CN 1297318C CN B021111316 A CNB021111316 A CN B021111316A CN 02111131 A CN02111131 A CN 02111131A CN 1297318 C CN1297318 C CN 1297318C
Authority
CN
China
Prior art keywords
liposome
shell type
core
hydroxyapatite
type nano
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.)
Expired - Fee Related
Application number
CNB021111316A
Other languages
Chinese (zh)
Other versions
CN1374132A (en
Inventor
储茂泉
徐宇虹
刘书朋
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanghai Jiaotong University
Original Assignee
Shanghai Jiaotong University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Shanghai Jiaotong University filed Critical Shanghai Jiaotong University
Priority to CNB021111316A priority Critical patent/CN1297318C/en
Publication of CN1374132A publication Critical patent/CN1374132A/en
Application granted granted Critical
Publication of CN1297318C publication Critical patent/CN1297318C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Nanotechnology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Manufacturing Of Micro-Capsules (AREA)

Abstract

The present invention relates to a method for preparing kernel and shell type nanometer compound particles of hydroxyapatite and liposome, which belongs to the field of biomedical engineering. The method takes a water phase in liposome as a microreactor and takes inorganic compounds as raw materials to synthesize kernel and shell type nanometer compound particles of hydroxyapatite and liposome with a kernel and shell type microstructure characteristic in a bionic way, and drugs can be loaded in the compound particles. The surfaces of the compound particles are connected with compounds with specific biological functions for carrying out surface modification to the compound particles. The method has substantive characteristics and obvious progresses. The liposome is a drug carrier with very good application prospect, and can change the body distribution characteristics of drugs. A liposome film has good biocompatibility, and can generate specificity effects in a body through a plurality of reaction mechanisms. The hydroxyapatite embedded in the liposome and provided by the method can be more effectively applied to the fields of cancer treatment, drug transmission and bone defect repair.

Description

The preparation method of the core-shell type nano composite particle of hydroxyapatite and liposome
Technical field: what the present invention relates to is a kind of preparation method of nano-complex particle, and the preparation method of the core-shell type nano composite particle of particularly a kind of hydroxyapatite and liposome belongs to biomedical engineering field.
Background technology: hydroxyapatite is the important inorganic constituents in humans and animals skeleton and the tooth, is the focus of studying in the technical field of biological material in recent years.The hydroxyapatite of synthetic is a kind of ideal bone substitution material, and can be used as the biological chromatography post and as the carrier of medicine especially cancer therapy drug.Current, more the someone proposes, and hydroxy-apatite has toxic action to multiple cancerous cell when nanoscale, and this peculiar effect needs hydroxyapatite to possess certain scale effect.Yet, nanoparticle is very unstable, be easy to assemble sedimentation, and hydroxyapatite is embarrassed the inorganic compound of water-soluble and organic solvent, if will really develop nanometer hydroxyapatite in pharmaceutically application, need with nanotechnology with biology knowledge merge the requirement of using on preparation method commonly used at present and the not exclusively suitable biological medicine.By literature search, still find no identical report with theme of the present invention, especially also very insufficient for its research of antitumaous effect, mechanism and medication aspect.
Summary of the invention: the present invention is directed to the deficiencies in the prior art, the preparation method of the core-shell type nano composite particle of a kind of hydroxyapatite and liposome is provided, prepare the stable, monodispersed hydroxyapatite of the controlled and granularity of a kind of pattern and the core-shell type nano composite particle of liposome, nano-complex particle can be applied among the damaged reparation of oncotherapy and bone better.The present invention is a microreactor with water in the liposome, with inorganic compound is reaction raw materials, synthetic have the hydroxyapatite of core-shell type microstructure characteristics and the core-shell type nano composite particle of liposome according to the biomineralization principle is bionical, and connect on the core-shell type nano composite particle surface have special biological function chemical compound so that compound particle is carried out finishing.
With water in the liposome is nano-reactor, synthetic nano-complex particle with core-shell type microstructure characteristics, be self-assembled into liposome with the matrix material for the liposome membrane material, with inorganic compound is that raw material synthesizing inorganic nanoparticle is a hydroxyapatite, with the liposome is housing, with synthetic hydroxyapatite nano particle is nuclear, forms the nano-complex particle with core-shell type microstructure characteristics.
Preparation method of the present invention is: one or more ionic liposome turbid liquors of the question response of preparation embedding earlier, the weeding of grease plastid is outer not by the ion of the question response of embedding, another kind of or several solions that add question response then, adjust reaction condition, mix to stir, promptly obtain the core-shell type nano composite particle of hydroxyapatite and liposome.
Carry out the ionic liposome turbid liquor of embedding question response freezing melt and dissolved, refrigerated temperature range is 0 ℃～-180 ℃, melt and dissolved temperature range is 0 ℃～100 ℃, freezing melt and dissolved number of times is 0～20 time, the weeding of grease plastid is outer not by the ion of the question response of embedding then, add another kind of or several solions of question response again, mix, promptly obtain the core-shell type nano composite particle of hydroxyapatite and liposome to stir.
The pH scope of the core-shell type nano composite particle of preparation hydroxyapatite and liposome is 0～14, temperature range is 0 ℃-100 ℃, Ca in the hydroxyapatite and the molar ratio range of P are 0.5～3, in the core-shell type nano composite particle of hydroxyapatite and liposome, the molar ratio range of calcium constituent and lipid material is 0.001～50000, this nano-complex particle is to exist with the suspension state, and the continuous phase of suspension is the normal saline or the buffer of deionized water or distilled water or 0.9%.
The inorganic compound raw material of synthesizing hydroxylapatite nanoparticle is meant: CaHPO 4, CaCl 2, Ca (NO 3) 2, Ca 3(PO 4) 2, CaO, Ca 4P 2O 9, NaOH, KOH, NH 3H 2O, NH 4OH, said liposome are that granularity is nanometer liposome, submicron liposome and the micron liposome between 5 nanometers to 100 micron.
The lipid film of compound particle (shell) constitute phospholipid molecule, glycolipid molecule, mullet alcohol molecule, cation lipid molecule, detergent molecule and amphiphilic polymer etc. and combination in any thereof.
The said nano-complex particle of the present invention is an assembling thing, and its structure is: the nuclear of nano-complex particle is synthetic hydroxyapatite nano particle, and housing is a liposome, and can be that functional modification is carried out in substrate with the liposome membrane.
Can also drug loading in the core-shell type compound particle and other active substances, medicine can be before hydroxyapatite be synthetic, among or add afterwards.
Core-shell type nano composite particle is carried out finishing to be meant in the liposome preparation process and to add decorative material, or synthetic reaction finishes back adding decorative material, carry out functional modification on the core-shell type nano composite particle surface, method of modifying comprises physical absorption and chemical reaction.
The functional molecular of compound particle finishing is a hydrophilic polymer, hydrophobic polymer, and part, antibody, cytokine, polypeptide, nucleic acid etc., and combination in any, molecular weight are 50-50000 dalton.They and surface molecular act as physical action, biological agent, or chemical bond-linking, the degree of modification on surface is the 0-99% mol ratio.
The functional molecular that when liposome membrane material film forming, adds finishing, perhaps after having formed core-shell type nano-complex particle suspension, the functional molecular that in this suspension, adds finishing, said functional molecular is a biocompatiblity molecules, hydrophilic polymer molecules, the binding specificity molecule, molten film molecule etc., and combination in any.
Described hydroxyapatite-liposome compound particle has stable, monodispersed particle size distribution, can have molecular recognition function, the targeting target by specificity in conjunction with being combined into specific superparticle structure, can be by cytophagy, and promote that Cytoplasm transports.
The bionical synthesizing hydroxylapatite nanoparticle of the present invention, its process comprise processes such as supramolecular pre-organized, interface molecular recognition and organic substrate modulation.Among the present invention, the lipid film material at first is self-assembled into supramolecular ordered body in water be liposome, and this provides a kind of nano-reactor environment for inorganic nano-particle synthetic.When liposome formed, the head group of phospholipid had been discerned the ion of question response in the solution with coordinate bond or electrostatic attraction, adds other ion of question response then, and itself and liposome interior ion are reacted.
Hydroxyapatite nano particle pan coating one deck liposome bimolecular tunic, the association force that causes because of high surface between nanoparticle played weaken and shielding action, simultaneously because the sterically hindered effect of liposome bimolecular tunic, make synthetic nanoparticle be difficult to assemble, thereby can obtain the stabilized nano particle, realize that the surface from the synthesizing nano-particle to the nanoparticle coats one and goes on foot new departure of finishing.Reuse has the chemical compound of special biological function to modify on synthetic core-shell type nano composite particle surface, to reach the needs of biologically using.
The present invention has substantive distinguishing features and marked improvement, liposome is a kind of pharmaceutical carrier with good application prospect, can change the interior distribution character of body of medicine, and Cytoplasm conveying characteristic, and liposome membrane has good biocompatibility, can specific effect take place in vivo by multiple reaction mechanism, especially have obvious advantages in a lot of diseases in treatment of cancer.
The specific embodiment: in conjunction with three embodiment are provided below the content of the present invention:
Embodiment 1: the 500mg soybean lecithin that will accurately take by weighing is dissolved in the round-bottomed flask that fills chloroform, and the following rotary evaporation of room temperature decompression is waved clean chloroform and become thin film, adds then and uses NH 3H 2The concentration that O transfers to the 50mL of pH=10 is 0.5moLL -1Ca (NO 3) 2Aqueous solution soaks, and film is washed into the milky suspension.This liposome turbid liquor is slowly flow through sodium type cation exchange column, under nitrogen protection, spare until suspension near clear suspension is newborn repeatedly again with the high pressure dispersing emulsification machine.Successively with the microporous filter membrane extruding of φ 0.65 μ m, φ 0.4 μ m, φ 0.2 μ m and φ 0.1 μ m, filtrate is slowly flow through cation exchange column again then, and the gained liposome turbid liquor is collected in the test tube and is stored in 2 ℃ the refrigerator standby.
Get embedding Ca 2+Liposome turbid liquor 2mL, wherein 1mL is with 100 times of deionized water dilutions, 1mL is diluted to 100 times of also ultra-sonic dispersion with 4% Triton X-100 aqueous solution in addition, so that liposome dissolving discharges Ca wherein 2+, detect Ca in these two kinds of solution respectively with ICP then 2+Concentration, obtain the Ca in outer water of liposome and the whole liposome turbid liquor 2+Concentration.
With embedding Ca 2+Liposome turbid liquor place conical flask, according to the Ca that measures 2+Concentration is used NH to wherein dripping 3H 2O transfers to pH=10's (NH 4) 2HPO 4Aqueous solution makes Ca/P=1.60 (mol/mol), and magnetic agitation drips off the back and continues to stir 30min, obtains the core-shell type nano composite particle suspension of hydroxyapatite-liposome.
Embodiment 2: the 500mg soybean lecithin adding that will accurately take by weighing fills in the round-bottomed flask of chloroform, and after waiting to dissolve, the following rotary evaporation of room temperature decompression is waved most chloroform and become thin film, and the mol ratio that adds pH=2 and Ca and P then is 5: 3 Ca (NO 3) 2With (NH 4) 2HPO 4Mixed aqueous solution, soak, and film washed into the milky suspension, this suspension is slowly flow through cation exchange column, with the Ca of the outer aqueous phase of weeding of grease plastid 2+Breast is even transparent until suspension repeatedly to suspension with the high pressure dispersing emulsification machine under nitrogen protection then, uses the filtering with microporous membrane of φ 0.4 μ m, φ 0.2 μ m and φ 0.1 μ m more respectively, and filtrate is slowly flow through cation exchange column again, promptly gets embedding Ca 2+And HPO 4 2-Liposome turbid liquor.To embedding Ca 2+And HPO 4 3-Liposome turbid liquor in drip NH 3H 2O, until the pH=10.30 of suspension, the room temperature lower magnetic force stirs, and promptly obtains the core-shell type nano composite particle suspension of hydroxyapatite-liposome.
Embodiment 3: the core-shell type nano composite particle suspension by embodiment 1 or embodiment 2 prepare hydroxyapatite and liposome adds DSPE-PEG, stirring then.Promptly get the surperficial hydroxyapatite of being modified by DSPE-PEG and the core-shell type nano composite particle suspension of liposome.
Perhaps add DSPE-PEG when liposome membrane material film forming, 500mg soybean lecithin that soon accurately takes by weighing and an amount of DSPE-PEG are dissolved in the round-bottomed flask that fills chloroform, and rotary evaporation is waved clean chloroform and become thin film under the room temperature decompression, adds Ca (NO again 3) 2Aqueous solution (embodiment 1) or Ca (NO 3) 2With (NH 4) 2HPO 4Mixed aqueous solution (embodiment 2), press the core-shell type nano composite particle suspension of embodiment 1 or embodiment 2 preparation hydroxyapatite and liposome then respectively.

Claims (7)

1, the preparation method of the core-shell type nano composite particle of a kind of hydroxyapatite and liposome, it is characterized in that, preparation method is specially: one or more ionic liposome turbid liquors of the question response of preparation embedding earlier, the weeding of grease plastid is outer not by the ion of the question response of embedding, another kind of or several solions that add question response then, adjust reaction condition, mix, promptly obtain the core-shell type nano composite particle of hydroxyapatite and liposome to stir;
Or one or more ionic liposome turbid liquors of the question response of preparation embedding earlier, carry out the ionic liposome turbid liquor of embedding question response freezing melt and dissolved, refrigerated temperature range is 0 ℃～-180 ℃, melt and dissolved temperature range is 0 ℃～100 ℃, freezing melt and dissolved number of times is 0～20 time, the weeding of grease plastid is outer not by the ion of the question response of embedding then, another kind of or several solions that add question response again, mix to stir, promptly obtain the core-shell type nano composite particle of hydroxyapatite and liposome;
In the core-shell type nano composite particle process of preparation hydroxyapatite and liposome, Ca in the hydroxyapatite and the molar ratio range of P are 0.5～3, the molar ratio range of calcium constituent in the core-shell type nano composite particle of hydroxyapatite and liposome and lipid material is 0.001～50000, this nano-complex particle is to exist with the suspension state, and the continuous phase of suspension is the normal saline or the buffer of deionized water or distilled water or 0.9%.
2, the preparation method of the core-shell type nano composite particle of this hydroxyapatite according to claim 1 and liposome, it is characterized in that compound particle lipid film (shell) constitute phospholipid molecule, glycolipid molecule, mullet alcohol molecule, cation lipid molecule, detergent molecule and amphiphilic polymer and combination in any thereof.
3, according to the preparation method of the core-shell type nano composite particle of described this hydroxyapatite of claim 1 and liposome, it is characterized in that in compound particle bag connects one or more medicines or other bioactive substance, bag connects form and comprises and be embedded in the liposome among the water or among hydroxyapatite or be embedded in the liposome membrane or with outer liposome surface and combine.
4, the preparation method of the core-shell type nano composite particle of this hydroxyapatite according to claim 1 and liposome, it is characterized in that core-shell type nano composite particle is carried out finishing to be meant in the liposome preparation process and to add decorative material, or synthetic reaction finishes back adding decorative material, carry out functional modification on the core-shell type nano composite particle surface, method of modifying comprises physical absorption and chemical reaction.
5, the preparation method of the core-shell type nano composite particle of this hydroxyapatite according to claim 1 and liposome, the functional molecular that it is characterized in that the compound particle finishing is a hydrophilic polymer, hydrophobic polymer, part, antibody, cytokine, polypeptide, nucleic acid, and combination in any, molecular weight is 50-50000 dalton. they and surface molecular act as physical action, biological agent, or chemical bond-linking, the degree of modification on surface is the 0-99% mol ratio.
6, the preparation method of the core-shell type nano composite particle of this hydroxyapatite according to claim 1 and liposome, it is characterized in that when liposome membrane material film forming, adding the functional molecular of finishing, perhaps after having formed core-shell type nano-complex particle suspension, the functional molecular that in this suspension, adds finishing, said functional molecular is a biocompatiblity molecules, hydrophilic polymer molecules, binding specificity molecule, molten film molecule, and combination in any.
7, the preparation method of the core-shell type nano composite particle of this hydroxyapatite according to claim 1 and liposome, it is characterized in that the bionical synthesizing hydroxylapatite nanoparticle of the present invention, its process comprises supramolecular pre-organized, interface molecular recognition and organic substrate modulated process.
CNB021111316A 2002-03-22 2002-03-22 Prepn of core-shell type nano compound hydroxyapatiti-liposome particle Expired - Fee Related CN1297318C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CNB021111316A CN1297318C (en) 2002-03-22 2002-03-22 Prepn of core-shell type nano compound hydroxyapatiti-liposome particle

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CNB021111316A CN1297318C (en) 2002-03-22 2002-03-22 Prepn of core-shell type nano compound hydroxyapatiti-liposome particle

Publications (2)

Publication Number Publication Date
CN1374132A CN1374132A (en) 2002-10-16
CN1297318C true CN1297318C (en) 2007-01-31

Family

ID=4741416

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB021111316A Expired - Fee Related CN1297318C (en) 2002-03-22 2002-03-22 Prepn of core-shell type nano compound hydroxyapatiti-liposome particle

Country Status (1)

Country Link
CN (1) CN1297318C (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040180091A1 (en) * 2003-03-13 2004-09-16 Chang-Yi Lin Carbonated hydroxyapatite-based microspherical composites for biomedical uses
CN1693415B (en) * 2005-04-29 2011-04-13 同济大学 Hydroxy phosphorite of near infrared fluorescence quantum point mark and its preparation process and application
DE102005022953A1 (en) * 2005-05-19 2006-11-23 Chemische Fabrik Budenheim Kg Dietary supplements
US8383175B2 (en) * 2006-12-12 2013-02-26 Firmenich Sa Active ingredient delivery system with an amorphous metal salt as carrier
CN102614549B (en) * 2012-03-07 2014-04-02 北京化工大学 Ferroferric oxide calcium phosphate nuclear shell magnetic nanoparticle and preparation method thereof by biological mineralization method
CN102671244B (en) * 2012-06-04 2015-01-21 广州迈普再生医学科技有限公司 Micro/nano-fiber bone repairing scaffold and production method thereof
CN104208754B (en) * 2014-09-19 2016-08-24 北京大学口腔医院 A kind of piezoelectric activity bone-repairing composite material and preparation method thereof
CN105249477B (en) * 2015-09-09 2018-01-30 江南大学 A kind of preparation method of slightly solubility calcium and the compound calcium reinforcing agent of phosphatide
CN108939155B (en) * 2017-05-17 2021-09-28 上海交通大学 Magnesium-based tissue engineering material antibacterial coating and preparation method thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4767615A (en) * 1984-05-03 1988-08-30 Technology Unlimited, Inc. Dental therapy by vesicle delivery
US4906670A (en) * 1986-03-25 1990-03-06 Rohto Pharmaceutical Co., Ltd. Pharmaceutical composition for the treatment of periodontal disease
CN1308016A (en) * 2000-11-10 2001-08-15 中国科学院上海硅酸盐研究所 Preparation of low temperature sinterable hydroxyapatite powder

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4767615A (en) * 1984-05-03 1988-08-30 Technology Unlimited, Inc. Dental therapy by vesicle delivery
US4906670A (en) * 1986-03-25 1990-03-06 Rohto Pharmaceutical Co., Ltd. Pharmaceutical composition for the treatment of periodontal disease
CN1308016A (en) * 2000-11-10 2001-08-15 中国科学院上海硅酸盐研究所 Preparation of low temperature sinterable hydroxyapatite powder

Also Published As

Publication number Publication date
CN1374132A (en) 2002-10-16

Similar Documents

Publication Publication Date Title
CN101287674B (en) Method for making chromonic nanoparticles
CN101340984B (en) Hierachical chromonic structures
CN100377745C (en) Stabilized medicine preparation form with by porous kietyoite covering flavour
CN102036652B (en) Be suitable for the cholesteric nanostructured of chelating
WO2004024209A2 (en) Materials and methods for drug delivery and uptake
CN100460016C (en) Meso-porous nanometer particle of calcium phosphate, its preparation method and application
EP1289642B2 (en) Nanocapsules having a polyelectrolyte envelope
EP2400957B1 (en) A controlled release micro-capsule for osteogenic action
US20050163714A1 (en) Capsules of multilayered neutral polymer films associated by hydrogen bonding
CN1297318C (en) Prepn of core-shell type nano compound hydroxyapatiti-liposome particle
CN101340898A (en) Multilayered chromonic structures
CN100571779C (en) alginate nano capsule and preparation method thereof
CN1299685C (en) Fluorouracil medicine carrier microsphere and production thereof
JPH04504120A (en) Method for producing ligand receptor composition
Sun et al. Dopamine-mediated biomineralization of calcium phosphate as a strategy to facilely synthesize functionalized hybrids
CN1686087A (en) Nano-magnetic medicinal microglobule, its preparation method and application
Onyekuru et al. An investigation of alkaline phosphatase enzymatic activity after electrospinning and electrospraying
Zhang et al. Emerging delivery systems based on aqueous two-phase systems: A review
CN100566708C (en) A kind of preparation method of hepatic targeting drug microcapsule
CN102476037A (en) Nano composite particle with controllable morphology and monodispersed granularity
Nagaich et al. Lipid grafts of egg-box complex: a new supramolecular biovector for 5-fluorouracil delivery
CN1380132A (en) Liposome and inorganic material core-shell type nano composite particle and its preparation method and application
Callewaert et al. Serum albumin-alginate coated microspheres: Role of the inner gel in binding and release of the KRFK peptide
Bahadur et al. Department of Pharmaceutics, Himalayan Pharmacy Institute, Rangpo, East Sikkim, India
Mahajan et al. A SYSTEMATIC REVIEW ON NANOCAPSULE

Legal Events

Date Code Title Description
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
C17 Cessation of patent right
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20070131

Termination date: 20130322