CN103006567A - Preparation method of hydrophilic-drug-entrapped chitosan-PLGA (poly(lactic-co-glycolic acid)) composite nanoparticles - Google Patents
Preparation method of hydrophilic-drug-entrapped chitosan-PLGA (poly(lactic-co-glycolic acid)) composite nanoparticles Download PDFInfo
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- CN103006567A CN103006567A CN2012105793551A CN201210579355A CN103006567A CN 103006567 A CN103006567 A CN 103006567A CN 2012105793551 A CN2012105793551 A CN 2012105793551A CN 201210579355 A CN201210579355 A CN 201210579355A CN 103006567 A CN103006567 A CN 103006567A
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Abstract
The invention provides a preparation method of novel hydrophilic-drug-entrapped chitosan-PLGA (poly(lactic-co-glycolic acid)) composite nanoparticles. The preparation method comprises the following steps: carrying out covalent crosslinking on chitosan and PLGA to obtain a polymer; carrying out ultrasonic treatment to obtain a hydrophilic-drug-carried self-assembled nano system; and carrying out ultracentrifugation, washing with deionized water, drying and the like to obtain the hydrophilic-drug-entrapped chitosan-PLGA composite nanoparticles. Compared with the traditional preparation technique, the invention eliminates the restriction and influence of the emulsification method on the hydrophilic drug entrapment, has the advantages of short preparation period, less drug loss, wide adaptability to hydrophilic drug entrapment, simple preparation technique, low manufacturing cost and the like, and is convenient to operate, thereby having favorable application prospects in research and development in the aspects of drug entrapment, drug release and the like.
Description
Technical field:
The present invention relates to organic nano medicine carrying field, be specially the preparation method that a kind of bag carries the chitosan-polylactic acid hydroxyacetic acid nanoparticle of hydrophilic medicament.
Background technology:
Chitosan (Chitosan) is by a kind of macromolecule glucosamine of the chitin in the dried small shrimps Carapax Eriocheir sinensis through obtaining after deacetylated.Chitosan has the characteristics such as good biocompatibility, biocidal property, degradability, it is applied on the various medical accessories on a large scale, as can be used as the main material that operation suture thread, artificial skin, burn-healing paste, chitosan also can prepare behind modifying and decorating becomes the carrier material that other have different effectiveness, such as hydrogel, micro materials, nano material etc.Polylactic-co-glycolic acid (PLGA) is equally as a kind of macromolecule organic material, have good biocompatibility, nontoxic, good encystation and the performance of film forming, be widely used in pharmacy, medical engineering material and modernized industrial field, and formally included into American Pharmacopeia as pharmaceutic adjuvant.
In recent years, the bag that has been successfully applied various medicines based on the PLGA micro-nano grain of rice of chitin modified modification carry and slow release on.This modifying and decorating generally is based on emulsified solvent volatilization technology and sets up, and the emulsion rule be search time the earliest, a kind of method for preparing micro-nano ball by emulsifying that range of application is the widest.Yet, in the existing research invention, no matter be the PLGA of unmodified or the PLGA micro-nano ball of chitin modified modification, they are multiplex in preparation fat-soluble medicine microball preparation, carry paclitaxel, camptothecine, dexamethasone, risperidone etc. as being used for bag, be used for wrapping the report that carries hydrophilic medicament less; The common methods that chitosan-PLGA carries the preparation of fat-soluble nanoparticle is: fat-soluble medicine is dissolved in the organic facies is stated from the blank PLGA nanoparticle by emulsion method bag, then utilize chitosan to its finishing, prepare the chitosan that is loaded with dewatering medicament-PLGA nanometer medicine-carried system.But in the emulsification method that adopts, PLGA and pharmaceutical aqueous solution form relatively difficulty of colostrum, and preparation process is complicated, easily causes drug loss in preparation process, causes drug efficiency low.Therefore, set up and a kind of the hydrophilic medicament bag carried simply, can effectively wrap carry hydrophilic medicament chitosan-PLGA composite Nano medicine carrying microgranule is significant.
Summary of the invention:
The preparation method that the purpose of this invention is to provide the chitosan that a kind of bag carries hydrophilic medicament-PLGA the Drug-loaded Nanoparticles is to remedy the deficiency of prior art.
The Drug-loaded Nanoparticles of the present invention is by medicine carrying and matrix composition, wherein different types of hydrophilic medicament is as the medicine carrying of nanoparticle, with biodegradable chitosan-PLGA copolymer as matrix, prepare target product with supersound process, namely carry the self-assembly chitosan of hydrophilic medicament-PLGA nanoparticle.Its concrete steps are: prepare chitosan-PLGA copolymer by the EDC catalysis process, copolymer and hydrophilic medicament are scattered in the deionized water, through supersound process, obtain being loaded with the self-assembling nano particles of hydrophilic medicament, ultracentrifugation, deionized water wash, drying namely obtains the chitosan that bag of the present invention carries hydrophilic medicament-PLGA the Drug-loaded Nanoparticles.
The present invention is used for base case polysaccharide-PLGA that bag carries hydrophilic medicament, all has widely material compatibility for chitosan and PLGA.The molecular weight of the chitosan of selecting-PLGA pharmaceutical carrier is between 20000～300000Da.The hydrophilic medicament that adopts can be one or more in doxorubicin hydrochloride, mitoxantrone hydrochloride, 5-fluorouracil, daunorubicin and the epirubicin.The present invention has removed emulsification method to restriction and impact that the hydrophilic medicament bag carries, has reduced drug loss, and the bag carrier of hydrophilic medicament is had widely adaptability, have easy to operate, the advantage such as preparing technique process is easy and cheap for manufacturing cost.
Significance of the present invention is to be different from fully the preparation of conventional chitosan-PLGA drug-carried nanometer, do not adopt traditional emulsifying technology, but by ultrasonic self-assembling method the hydrophilic medicament bag is stated from chitosan-PLGA nanoparticle, make the chitosan that carries hydrophilic drugs-PLGA drug-carried nanometer, improved chitosan-PLGA the bag of hydrophilic drugs is carried efficient.Owing to having adopted ultrasonic self-assembling technique, product to have preferably drug loading and envelop rate, have good research and development application prospect at drug encapsulation and drug release etc. aspect many, therefore, the technology of the present invention has good potentiality of economical exploit.
The specific embodiment
Be described more specifically content of the present invention below in conjunction with example:
At first adopting chitosan and PLGA is raw material, both copolymers of preparation under EDC catalysis, and the substitution value of PLGA is 5%～30% in the copolymer.The molecular weight of copolymer is at 20000～300000Da.
Under the neutrallty condition, hydrophilic medicament doxorubicin hydrochloride, mitoxantrone hydrochloride, 5-fluorouracil, daunorubicin or epirubicin are dissolved in the deionized water of chitosan-containing-PLGA copolymer, wherein the mass ratio of copolymer and medicine was 1～100: 1, with 20～80w power ultrasonic 2～8 minutes.12000 rev/mins of ultracentrifugations removed supernatant in 15 minutes, and washed with de-ionized water is fallen free drug, and centrifugal collecting precipitation is drying to obtain target product.
Embodiment 1:
Taking by weighing 1 part of molecular weight and be the 20000Da substitution value and be 5% chitosan-PLGA copolymer is scattered in the deionized water, under stirring condition, add 1 part of doxorubicin hydrochloride, 20w power ultrasonic 2 minutes, 12000 rev/mins centrifugal 15 minutes, supernatant discarded, washed with de-ionized water is fallen free drug, and centrifugal collecting precipitation is drying to obtain the chitosan that carries doxorubicin hydrochloride-PLGA nanoparticle.
Embodiment 2:
Taking by weighing 20 parts of molecular weight and be the 100000Da substitution value and be 15% chitosan-PLGA copolymer is scattered in the deionized water, under stirring condition, add 2 parts of mitoxantrone hydrochlorides, 50w power ultrasonic 5 minutes, 12000 rev/mins centrifugal 15 minutes, supernatant discarded, washed with de-ionized water is fallen free drug, and centrifugal collecting precipitation is drying to obtain the chitosan that carries mitoxantrone hydrochloride-PLGA nanoparticle.
Embodiment 3:
Taking by weighing 100 parts of molecular weight and be the 200000Da substitution value and be 30% chitosan-PLGA copolymer is scattered in the deionized water, under stirring condition, add 1 part of 5-fluorouracil, 80w power ultrasonic 8 minutes, 12000 rev/mins centrifugal 15 minutes, supernatant discarded, washed with de-ionized water is fallen free drug, and centrifugal collecting precipitation is drying to obtain the chitosan that carries 5-fluorouracil-PLGA nanoparticle.
Embodiment 4:
Taking by weighing 50 parts of molecular weight and be the 300000Da substitution value and be 25% chitosan-PLGA copolymer is scattered in the deionized water, under stirring condition, add 1 part of daunorubicin, 20w power ultrasonic 8 minutes, 12000 rev/mins centrifugal 15 minutes, supernatant discarded, washed with de-ionized water is fallen free drug, and centrifugal collecting precipitation is drying to obtain the chitosan that carries daunorubicin-PLGA nanoparticle.
Embodiment 5:
Taking by weighing 100 parts of molecular weight and be the 100000Da substitution value and be 25% chitosan-PLGA copolymer is scattered in the deionized water, under stirring condition, add 5 parts of epirubicins, 50w power ultrasonic 5 minutes, 12000 rev/mins centrifugal 15 minutes, supernatant discarded, washed with de-ionized water is fallen free drug, and centrifugal collecting precipitation is drying to obtain the chitosan that carries epirubicin-PLGA nanoparticle.
Embodiment 6:
Taking by weighing 80 parts of molecular weight and be the 200000Da substitution value and be 15% chitosan-PLGA copolymer is scattered in the deionized water, under stirring condition, add 1 part of doxorubicin hydrochloride, 80w power ultrasonic 8 minutes, 12000 rev/mins centrifugal 15 minutes, supernatant discarded, washed with de-ionized water is fallen free drug, and centrifugal collecting precipitation is drying to obtain the chitosan that carries doxorubicin hydrochloride-PLGA nanoparticle.
Claims (5)
1. preparation method that bag carries the chitosan-polylactic acid hydroxyacetic acid composite nano particle of hydrophilic medicament, it is characterized in that described the Drug-loaded Nanoparticles is by medicine carrying and matrix composition, wherein different types of hydrophilic medicament is as the medicine carrying of nanoparticle, with biodegradable chitosan-polylactic acid co-glycolic acid as matrix, prepare target product with supersound process, namely carry the self-assembly chitosan of hydrophilic medicament-polylactic-co-glycolic acid nanoparticle.Its concrete steps are: prepare the chitosan-polylactic acid co-glycolic acid by the EDC catalysis process, copolymer and hydrophilic medicament are scattered in the deionized water, through supersound process, obtain being loaded with the self-assembled nanometer system of hydrophilic medicament, behind the ultracentrifugation, remove free drug with deionized water wash, drying namely obtains the chitosan-polylactic acid hydroxyacetic acid nanoparticle that bag of the present invention carries hydrophilic medicament.
2. the preparation method of the chitosan-polylactic acid hydroxyacetic acid composite nano particle of as claimed in claim 1 year hydrophilic medicament, the substitution value that it is characterized in that PLGA in the prepared chitosan-polylactic acid co-glycolic acid is 5%～30%, and molecular weight of copolymer is at 20000～300000Da.
3. the preparation method of the chitosan-polylactic acid hydroxyacetic acid composite nano particle of as claimed in claim 1 year hydrophilic medicament, the mass ratio that it is characterized in that described chitosan-polylactic acid co-glycolic acid and hydrophilic medicament is 1～100: 1.
4. the preparation method of the chitosan-polylactic acid hydroxyacetic acid composite nano particle of as claimed in claim 1 year hydrophilic medicament is characterized in that described ultrasonic power is 20～80w, and ultrasonic time is 2～8 minutes.
5. the preparation method of the chitosan-polylactic acid hydroxyacetic acid composite nano particle of as claimed in claim 1 year hydrophilic medicament is characterized in that described hydrophilic medicament can be one or more in doxorubicin hydrochloride, mitoxantrone hydrochloride, 5-fluorouracil, daunorubicin and the epirubicin.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104001178A (en) * | 2014-05-19 | 2014-08-27 | 中山大学 | Polylactic acid-hydroxyacetic acid copolymer nano-drug carrier as well as preparation method and application thereof |
| CN105060508A (en) * | 2015-09-14 | 2015-11-18 | 湖州道场污水处理有限公司 | Biological sewage-treatment complex microbial inoculant and preparation method thereof |
| WO2020223158A1 (en) * | 2019-04-30 | 2020-11-05 | The Medical College Of Wisconsin, Inc. | Trans-tympanic membrane delivery platform and uses thereof |
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| CN101366700A (en) * | 2008-09-19 | 2009-02-18 | 浙江大学 | Hydrophilic medicament dual-microsphere formulation and preparation method thereof |
| CN101969934A (en) * | 2007-12-13 | 2011-02-09 | 国立大学法人九州大学 | Drug-containing nanoparticles |
| US20110142947A1 (en) * | 2009-06-08 | 2011-06-16 | Leo Rubin | Novel formulations |
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| CN101969934A (en) * | 2007-12-13 | 2011-02-09 | 国立大学法人九州大学 | Drug-containing nanoparticles |
| CN101366700A (en) * | 2008-09-19 | 2009-02-18 | 浙江大学 | Hydrophilic medicament dual-microsphere formulation and preparation method thereof |
| US20110142947A1 (en) * | 2009-06-08 | 2011-06-16 | Leo Rubin | Novel formulations |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104001178A (en) * | 2014-05-19 | 2014-08-27 | 中山大学 | Polylactic acid-hydroxyacetic acid copolymer nano-drug carrier as well as preparation method and application thereof |
| CN105060508A (en) * | 2015-09-14 | 2015-11-18 | 湖州道场污水处理有限公司 | Biological sewage-treatment complex microbial inoculant and preparation method thereof |
| WO2020223158A1 (en) * | 2019-04-30 | 2020-11-05 | The Medical College Of Wisconsin, Inc. | Trans-tympanic membrane delivery platform and uses thereof |
| US11197820B2 (en) * | 2019-04-30 | 2021-12-14 | The Medical College Of Wisconsin, Inc. | Trans-tympanic membrane delivery platform and uses thereof |
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Application publication date: 20130403 |