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Agglutinin-modified drug delivery system from nose to brain

A delivery system and lectin technology, applied in the field of chemical pharmaceuticals, can solve the problems of non-specificity and location, unsatisfactory residence time, increase the absorption of drug carriers, etc., so as to increase the amount of brain entry, reduce the effect of treatment and diagnosis, and reduce the Effects of systemic toxicity

Inactive Publication Date: 2006-10-04
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the adhesion function of these bioadhesive materials is often based on their interaction with mucus in the nasal cavity, such as electrostatic interaction, which is often not specific and site-selective, and cannot selectively increase the ability to mediate drugs into the brain. Absorption of Drug Carriers by Olfactory Mucosa
At the same time, due to the rapid renewal of mucus in the nasal cavity, usually there are multiple renewals within an hour, the effect of prolonging the residence time of the drug delivery system in the nasal cavity based on the bioadhesion of mucus is not effective. very ideal

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1: Construction of lectin-modified nanoparticle drug delivery system and its influencing factors

[0035] 1) Thihydration of wheat germ agglutinin (WGA): Dissolve different amounts of WGA in 1ml of sodium borate solution with pH=8.0, add excess thiolation reagent 2-iminothiolane hydrochloride (2-IT), and stir magnetically at low speed for 1 hour. The desalting column separates the thiolated protein and the unreacted thiolated reagent. The degree of sulfhydrylation of WGA measured by Ellman's reagent was between 0.2-5mol thiol / mol protein.

[0036] 2) Preparation of PEGylated nanoparticles (NP): Add 50 μl of distilled water to 1 ml containing different proportions of monomethoxypolyethylene glycol-polylactic acid (MPEG-PLA), maleimide-polyethylene glycol-polylactic acid ( In the dichloromethane solution of Mal-PEG-PLA) block copolymer, 220W continuous ultrasonication for 30s was used to prepare w / o type colostrum. Add colostrum into 2ml of 1% sodium cholate sol...

Embodiment 2

[0040] Example 2: Targeting evaluation of lectin-modified nanoparticles loaded with fluorescent probe 6-coumarin in rat brain

[0041] 1) The fluorescent probe-loaded 6-coumarin WGA-NP, Ume agglutinin-modified nanoparticles (UEA-NP) and lentil bean agglutinin-modified nanoparticles (DBA-NP) were prepared respectively according to the method of Example 1.

[0042] 2) The number average particle diameters of WGA-NP, UEA-NP, DBA-P and NP measured by Zeta Potential / Particle Sizer NICOMPTM 380ZLS and loaded with 6-coumarin are 80-90nm, 84-95nm, 80-94nm respectively and 70-80nm.

[0043] 3) The in vitro leakage of 6-coumarin loaded on NP and lectin-modified nanoparticles was measured under the conditions of pH7.4 and pH4.0PBS sink respectively. The results showed that the leakage of 6-coumarin contained in the two media Both are low (not more than 4% in 24 hours), so 6-coumarin is an ideal fluorescent probe, which can be used to trace the transport of nanoparticles in rats.

[004...

Embodiment 3

[0057] Example 3: Preparation of a drug delivery system loaded with the cerebral vasodilator nimodipine

[0058] 1) Thiolation of lectin: Weigh an appropriate amount of lectin, add HEPES solution (pH 7.4) to dissolve and dilute to make a 0.2-5mg / ml solution, add appropriate amount of S-acetyl-thioglycolic acid-N-succinimide (SATA) dimethyl sulfoxide solution, stirred for 30 min, and ultrafiltered to remove dimethyl sulfoxide. An appropriate amount of hydroxylamine was added to each milliliter of lectin solution to react for 30 minutes to obtain thiolated lectin. The degree of thiolation of lectin determined by Ellman's reagent is between 0.2-5 mol thiol / mol protein.

[0059] 2) Preparation of Nimodipine-loaded nanoparticles by phase separation-dialysis

[0060] Dissolve 0.2g of MPEG-PLA, 0.02g of maleimide-PEG-PLA block copolymer and 0.1g of nimodipine in 6ml of DMF, slowly add it dropwise into 14ml of water while stirring, put the obtained emulsion into a dialysis bag, and ...

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Abstract

This invention belongs to chemistry pharmaceutical field and relates to a medication transfer system, especially relates to an agglutinin masked medication-load transfer mechanism transferring from nose to brain. This invention comprises medication carrier nanograin, vesicle or lipid body surface finish agglutinin. By using the transfer system, resort time of medication-load system on nasal mucosa can be prolonged, dielectric mucosa absorb the medication-load system and selectively deliver small molecular chemistry medication, diagnosis medication, polypeptide proteins and gene medication into brain. This invention can deliver more medication into brain and relatively decrease medication in outer tissue, so it can depress toxic action at every pore while toning up prevention, cure and diagnosis effect of backbone diseases.

Description

technical field [0001] The invention belongs to the field of chemical pharmacy and relates to a drug delivery system, in particular to a lectin-modified drug delivery system through the nose into the brain. technical background [0002] The blood-brain barrier (BBB) ​​is a layer of barrier system between blood and brain tissue. It is composed of polarized brain capillary endothelial cells through complex intercellular tight junctions. It is very important for maintaining the relative stability of the brain environment. , but it is also the main barrier for drugs to enter the brain tissue for prevention, treatment and diagnosis. [0003] In order to achieve drug delivery in the brain, a variety of brain targeted drug delivery strategies have been applied, such as drug esterification modification and chemical delivery system, carrier, receptor and adsorption-mediated brain targeted drug delivery system, nasal cavity medication etc. Among them, only nasal administration is a ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K9/14A61K9/00A61K38/16A61K47/34A61P25/00
Inventor 高小玲蒋新国陶炜兴张奇志陆伟
Owner FUDAN UNIV
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