CN104945571B - The preparation method of pH responsive polymer base Janus hollow nanospheres - Google Patents

The preparation method of pH responsive polymer base Janus hollow nanospheres Download PDF

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CN104945571B
CN104945571B CN201510340704.8A CN201510340704A CN104945571B CN 104945571 B CN104945571 B CN 104945571B CN 201510340704 A CN201510340704 A CN 201510340704A CN 104945571 B CN104945571 B CN 104945571B
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CN104945571A (en
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张国林
夏志佳
吴秋华
刘学
矣杰
宋溪明
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Liaoning University
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Abstract

The present invention relates to the preparation method of pH responsive polymer base Janus hollow nanospheres.Using Nano particles of silicon dioxide SNP as template, hydroxy kind initiator is introduced on its surface, using obtained SNP OH as initiator, stannous octoate is catalyst, triggers DL lactide ring-opening polymerisations, obtains SNP g PLA；SNP g PLA are modified using ɑ bromo isobutyl acylbromides, obtain SNP g PLA Br；Using DEAEMA as monomer, Me6TREN is ligand, and CuBr is catalyst, is merged by ATRP activity polies using EGDMA as crosslinking agent and polymeric layer is crosslinked, obtain SNP g PLA b cPDEAEMA.Finally silica template is performed etching with hydrofluoric acid, obtains target product.The product of the present invention, using Janus hollow structures loading and transport materials, realizes the material transmission of shell internal and external environment.

Description

The preparation method of pH responsive polymer base Janus hollow nanospheres
Technical field
The invention belongs to the field of chemical synthesis, has more particularly to one kind in Janus nanometers of pH responsive polymer bases The preparation method of empty ball.
Background technology
Janus materials refer to possess two kinds of different structures and the anisotropic material of chemical composition at the same time.This asymmetry Asymmetry on property, such as hydrophilic-hydrophobic, positive charge-negative electrical charge, polar-nonpolar and pattern, all imparts The special feature of Janus materials, can meet the needs under complicated environmental condition.
Janus hollow balls are suffered from because of the cavity body structure having inside it in fields such as chemistry, materialogy, biochemistries Important application, for example, it is miniature limited reactor, catalysis material, heat preserving and insulating material and biological medicine slow-release material, artificial thin Born of the same parents etc..Using hollow structure loading and transport materials, the material transmission of shell internal and external environment is realized, therefore external and internal compositions pass through Logical hollow ball is upper more advantageous in application.If the certain environment-responsive of the shell structurre for assigning Janus hollow balls, can To regulate and control the material transmission inside and outside shell according to the microenvironment residing for hollow nanosphere.
The content of the invention
The object of the present invention is to provide one kind using Janus hollow structures loading and transport materials, shell inner and outer ring is realized The preparation method with pH responsive polymer base Janus hollow nanospheres of the material transmission in border.
To achieve these goals, the technical solution adopted by the present invention is：A kind of Janus nanometers of pH responsive polymers base The preparation method of hollow ball, includes the following steps：
1) with Nano particles of silicon dioxide (SNP) for template, hydroxy kind initiator is introduced on its surface, obtains intermediate 1 (SNP-OH)；
2) with intermediate 1 (SNP-OH) for initiator, stannous octoate (Sn (Oct)2) it is catalyst, trigger DL- lactides (DL-LA) ring-opening polymerisation, obtains intermediate 2 (SNP-g-PLA)；
3) ATRP (atom transfer radical polymerization) is carried out with ɑ-bromo isobutyl acylbromide centering mesosome 2 (SNP-g-PLA) to change Property, obtain intermediate 3 (SNP-g-PLA-Br)；
4) with intermediate 3 (SNP-g-PLA-Br) for initiator, there is the methacrylic acid lignocaine second of pH responses Ester (DEAEMA) is monomer, three (2- dimethylaminoethyls) amine (Me6TREN) it is ligand, cuprous bromide (CuBr) is catalyst, By atom transfer radical polymerization (ATRP), and with ethylene glycol dimethacrylate (EGDMA) for crosslinking agent to polymer Layer is crosslinked, and obtains intermediate 4 (SNP-g-PLA-b-cPDEAEMA)；
5) intermediate 4 (SNP-g-PLA-b-cPDEAEMA) is used into hf etching at room temperature, obtains target product.
The preparation method of above-mentioned pH responsive polymer base Janus hollow nanospheres, the step 1) include as follows Step：
1.1) ethanol, ammonium hydroxide and deionized water are added in single-necked flask, stirred evenly, then instill positive silicic acid dropwise The ethanol solution of tetra-ethyl ester, when 30-40 DEG C of reaction 10-15 is small under magnetic agitation.Reaction mixture is centrifuged, to remove upper strata clear Liquid, collects white solid and obtains Nano particles of silicon dioxide (SNP).
1.2) Nano particles of silicon dioxide (SNP) is added in ethanol, ultrasonic disperse, then adds γ-aminopropyl three Ethoxysilane, N2Under protection, when 60-80 DEG C of magnetic agitation reaction 40-50 is small.Reaction mixture is centrifuged, to remove upper strata clear Liquid, collects solid and obtains the Nano-meter SiO_2 of surface amino groups modification2Microballoon (SNP-NH2)。
1.3) Nano particles of silicon dioxide and dimethylbenzene being modified surface amino groups mix, and ultrasonic disperse, adds hydroxy kind Initiator, vacuumizes, and leads to nitrogen, under nitrogen protection, when 60-65 DEG C of reaction 18-24 is small.Reaction mixture is centrifuged, is removed Supernatant, collects solid and obtains intermediate 1 (SNP-OH).
The preparation method of above-mentioned pH responsive polymer base Janus hollow nanospheres, the hydroxy kind initiator are Glycidol, the Nano-meter SiO_2 that surface amino groups are modified2The mass ratio of microballoon and glycidol is：2:0.8-1；It is preferred that 2:1.
The preparation method of above-mentioned pH responsive polymer base Janus hollow nanospheres, the step 2) include as follows Step：By intermediate 1, DL- lactides and dimethylformamide (DMF) in container, ultrasonic disperse, is added dropwise stannous octoate, takes out Vacuum, leads to nitrogen, under nitrogen protection, when 125-130 DEG C of reaction 45-50 is small, obtains intermediate 2 (SNP-g-PLA).
The preparation method of above-mentioned pH responsive polymer base Janus hollow nanospheres, intermediate 1 (SNP-OH) and DL- The mass ratio of lactide is：1:14-16；It is preferred that 1:16.
The preparation method of above-mentioned pH responsive polymer base Janus hollow nanospheres, the step 3) include as follows Step：By intermediate 2 (SNP-g-PLA) and dry CH2Cl2Mixing, ultrasonic disperse, added under ice-water bath triethylamine and ɑ- Bromo isobutyl acylbromide, react in ice-water bath 1-2 it is small when, then in react at room temperature 45-50 it is small when.Reaction mixture is centrifuged, is removed Supernatant is removed, solid is collected and obtains intermediate 3 (SNP-g-PLA-Br).
The preparation method of above-mentioned pH responsive polymer base Janus hollow nanospheres, intermediate 2 (SNP-g-PLA) with The mass ratio of ɑ-bromo isobutyl acylbromide is：1:16-20；It is preferred that 1:20.
The preparation method of above-mentioned pH responsive polymer base Janus hollow nanospheres, the step 4) include as follows Step：By intermediate 3 (SNP-g-PLA-Br), DEAEMA, EGDMA, Me6TREN is mixed with dry DMF, ultrasonic disperse, liquid Chilled nitrogen, vacuumizes, and melts, and circulating liquid nitrogen freezes-vacuumizing-and melts three times, adds CuBr, then to carry out liquid nitrogen frozen-pumping true Sky-thawing, the then tube sealing under the state that vacuumizes, when 70-75 DEG C of reaction 18-24 is small.Reaction mixture is centrifuged, removes supernatant Liquid, collects solid and obtains intermediate 4 (SNP-g-PLA-b-cPDEAEMA).
The preparation method of above-mentioned pH responsive polymer base Janus hollow nanospheres, intermediate 3 (SNP-g-PLA-Br) Mass ratio with DEAEMA is：1:14-16, preferably 1:16；The molar ratio of DEAEMA and EGDMA is：8-10:1, preferably 8:1.
The preparation method of above-mentioned pH responsive polymer base Janus hollow nanospheres, the concentration expressed in percentage by volume of hydrofluoric acid For 10%-50%.
Target product pH responsive polymer base Janus hollow nanospheres prepared by method using the present invention are hollow knot Structure, internal layer are hydrophobic degradable polylactic acid, and outer layer is the crosslinked polymethylacrylic acid diethylamino with pH responses Base ethyl ester.
Polylactic acid (PLA) has the fast characteristic of degradation rate and good biocompatibility, is degraded most in body End-product is CO2And H2O.There is extensive use in fields such as environmental protection, organizational project, Fracture internal fixaiion and medicine controlled releasings.
Polymethylacrylic acid lignocaine ethyl ester (PDEAEMA) is a kind of polymer with pH responses, and Pka is about 7.2, when pKa is less than 7.2, PDEAEMA is protonated, and for soluble weak cation electrolyte, hydrophily, polymerization is presented Thing chain is unfolded；When pKa is higher than 7.2, PDEAEMA deprotonations, are presented hydrophobic state, polymer chain is shunk, in intelligent section bar Have a wide range of applications in terms of material.
The beneficial effects of the invention are as follows：The SNP-OH obtained by Nano particles of silicon dioxide conducting modification of surface hydroxy group, can fit Trigger the lactone of ring-opening polymerisation for any hydroxyl, it is modified by ATRP, suitable for the controllable polymerization of most of monomers, such as first Base acrylate, acrylate and styrene etc..
From the point of view of building-up process, using silica as template, the ring-opening polymerisation grafting PLA after amino, hydroxyl modification；Pass through again ATRP initiators are modified, and pass through the PDEAEMA of ATRP polymerization and crosslinking with pH responses；Most etch to obtain with pH through HF afterwards The Janus hollow nanospheres of response.Scanning electron microscope and transmission electron microscope show that this method can obtain Janus hollow nanos Ball, illustrates the feasibility of the method.It is this that Janus hollow nanospheres are formed by PLA/PDEAEMA, since it is with pH responses Property, biological degradability and good biocompatibility, have good application prospect in the field such as drug delivery and controlled release.
From structure and principle, pH responsive polymer base Janus hollow nanospheres prepared by the present invention are hollow ball Shape material.Since inner side has degradability, hydrophobicity, good biocompatibility, outside has pH responses, and utilization is hollow Structure loads and transport materials, realizes the material transmission of shell internal and external environment, and the hollow ball of external and internal compositions perforation is upper more in application With advantage, so there is good application prospect in the field such as drug delivery and controlled release.
Brief description of the drawings
Fig. 1 a are the Zeta potential figures of SNP.
Fig. 1 b are SNP-NH2Zeta potential figure.
Fig. 2 is SNP (a), SNP-NH2(b), SNP-OH (c), SNP-g-PLA (d), SNP-g-PLA-Br (e) and SNP-g- The infrared spectrogram of PLA-b-cPDEAEMA1 (f).
Fig. 3 is the thermal gravimetric analysis curve figure of SNP (a), SNP-g-PLA (b) and SNP-g-PLA-b-cPDEAEMA1 (c).
Fig. 4 is SNP (a), SNP-g-PLA (b), SNP-g-PLA-b-cPDEAEMA1 (c), pH responsive polymer bases The scanning electron microscope (SEM) photograph of Janus hollow nanosphere PLA-b-cPDEAEMA1 (d).
Fig. 5 is SNP (a), SNP-g-PLA (b), SNP-g-PLA-b-cPDEAEMA1 (c), pH responsive polymer bases The transmission electron microscope picture of Janus hollow nanosphere PLA-b-cPDEAEMA1 (d).
Embodiment
The preparation of 1 pH responsive polymer base Janus hollow nanospheres PLA-b-cPDEAEMA1 of embodiment
(1) synthesis of SNP-OH
1st, the preparation of Nano particles of silicon dioxide (SNP)
42.6g ethanol, 25% ammonium hydroxide of 25g and 9.75g water are weighed respectively, are put into 250mL round-bottomed flasks, are stirred evenly. 7.7g tetraethyl orthosilicates (TEOS) and 30g ethanol are uniformly mixed, are placed in dropping funel, is instilled dropwise in round-bottomed flask, When the lower 35 DEG C of reactions 12 of magnetic agitation are small.After reaction, reaction mixture centrifuged, remove supernatant, white solid second Alcohol is 9 with water volume ratio:1 mixed solution washing three times, obtains 2.0g Nano particles of silicon dioxide (SNP).Product is put into vacuum Drying box, under the conditions of 50 DEG C it is dry 24 it is small when, it is spare.Synthetic route is as follows：
2nd, the Nano-meter SiO_2 that surface amino groups are modified2Microballoon (SNP-NH2) preparation
1.5g Nano particles of silicon dioxide (SNP) is weighed in 100mL three-neck flasks, adds 70mL absolute ethyl alcohols, ultrasound It is complete to disperseing.1.5g gamma-aminopropyl-triethoxy-silanes (APTES), N is added dropwise2Under protection, when 70 DEG C of reactions 48 are small. After reaction, reaction mixture centrifuged, remove supernatant, white solid is washed with ethanol and obtains 1.8g SNP-NH three times2。 Product is put into vacuum drying chamber, under the conditions of 50 DEG C it is dry 24 it is small when, it is spare.Synthetic route is as follows：
3rd, the Nano-meter SiO_2 of hydroxyl modification2The preparation of microballoon (SNP-OH)
Weigh 1.0g SNP-NH2In 50mL eggplant-shape bottles, 25mL anhydrous dimethyl benzene is added, ultrasound is complete to disperseing.Add 0.5g glycidols, vacuumize, and lead to N2, vacuumize repeatedly-lead to N2Three times, finally in N2Under protection, when 65 DEG C of reactions 24 are small.Instead After answering, reaction mixture is centrifuged, removes supernatant, white solid is washed three times with dimethylbenzene, then is washed with THF, weight This multiple operation three times, obtains 1.2g SNP-OH.Product is put into vacuum drying chamber, under the conditions of 50 DEG C it is dry 24 it is small when, it is spare.Synthesis Route is as follows：
(2) synthesis of SNP-g-PLA
0.1g SNP-OH, 1.4g DL- lactides are weighed in 50mL polymerization pipes, adds 15mL anhydrous DMFs, ultrasound is extremely divided Clear complete.36mg Sn (Oct) are added dropwise2, vacuumize, lead to N2, vacuumize repeatedly-lead to N2Three times, finally in N2Under protection, 125 DEG C React 48 it is small when.After reaction, reaction mixture centrifuged, remove supernatant, solid is washed with DMF, is centrifuged, is removed supernatant Liquid, repetitive operation is three times.Solid is washed with THF again, is centrifuged, is removed supernatant, repetitive operation is three times.Solid vacuum at 50 DEG C Drying 24 obtains 0.15g SNP-g-PLA when small.Product is put into vacuum drying chamber, under the conditions of 50 DEG C it is dry 24 it is small when, it is spare.Synthesis Route is as follows：
(3) synthesis of SNP-g-PLA-Br
0.1g SNP-g-PLA are weighed in 100mL round-bottomed flasks, add the anhydrous CH of 25mL2Cl2, ultrasound to being completely dispersed, 30min is stirred in ice-water bath, adds 1.5mL triethylamines, 1.5mL ɑ-bromo isobutyl acylbromide, continue at and 2 are reacted in ice-water bath Hour, then move on at room temperature reaction 48 it is small when.After reaction, reaction mixture centrifuged, remove supernatant.Solid is used CH2Cl2Washing, centrifugation, remove supernatant, and repetitive operation is three times.Solid is washed with THF again, is centrifuged, is removed supernatant, repeats to grasp Make three times, to obtain 0.12g SNP-g-PLA-Br.Product is put into vacuum drying chamber, under the conditions of 50 DEG C it is dry 24 it is small when, it is spare.Synthesis Route is as follows：
(4) preparation of SNP-g-PLA-b-cPDEAEMA1
0.1g SNP-g-PLA-Br are weighed in 50mL polymerization pipes, add 8mL anhydrous DMFs, 1.6g DEAEMA, 0.22g EGDMA、0.036g Me6TREN, ultrasound add liquid nitrogen frozen, vacuumize, melt completely to scattered, and repeated freezing-vacuumize- The circulation of thawing is three times.Then, 0.028g CuBr are added, then freeze-vacuumize-thaw cycle once, vacuumizing shape Tube sealing under state, when 70 DEG C of reactions 24 are small.After reaction, system is opened wide, terminates polymerization.Reaction mixture is centrifuged, in removing Clear liquid, solid are washed with THF, are centrifuged off supernatant, and repetitive operation three times, obtains 0.15g SNP-g-PLA-b-cPDEAEMA1. Product is put into vacuum drying chamber, under the conditions of 50 DEG C it is dry 24 it is small when, it is spare.Synthetic route is as follows：
(5) preparation of pH responsive polymers base Janus hollow nanospheres PLA-b-cPDEAEMA1
0.05g SNP-g-PLA-b-cPDEAEMA1 are weighed in 100mL centrifuge tubes, add 10mL ultra-pure waters, ultrasound is extremely Be completely dispersed, add 10mL 40%HF etch at room temperature 24 it is small when.Reaction mixture is centrifuged, removes supernatant, solid Washed three times with absolute ethyl alcohol again, obtain 0.01g pH responsive polymer base Janus hollow nanospheres PLA-b-cPDEAEMA1. Synthetic route is as follows：
(6) testing result
Under conditions of Fig. 1 a are pH=6, the Zeta potential figure of SNP, Fig. 1 b are SNP-NH2Zeta potential figure.Before modified SiO2The Zeta potential of nano-particle is -31mV, the SiO after amino modified2The Zeta potential of nano-particle is 17.5mV, Zeta potential is become just by negative.This is because in pH=6, SiO before modified2Nanoparticle surface has great amount of hydroxy group elecrtonegativity base Group, Zeta potential is negative；SiO after amino modified2Nanoparticle surface contains a large amount of amino and is protonated, and shows electropositive, Zeta potential be on the occasion of.
Fig. 2 is (a) SNP, (b) SNP-NH2, (c) SNP-OH, (d) SNP-g-PLA, (e) SNP-g-PLA-Br and (f) The infrared spectrogram of SNP-g-PLA-b-cPDEAEMA1.Wherein (a) is SiO2The infrared spectrum of nano-particle, 1100cm-1With 800cm-1Place belongs to antisymmetric stretching vibration and the symmetrical stretching vibration of Si-O-Si keys, 471cm-1Place belongs to Si-O-Si The flexural vibrations of key, absworption peak is the characteristic absorption peak of Nano particles of silicon dioxide at the above three.(b), (c) to be amino modified and SiO after hydroxyl modification2The infrared spectrum of nano-particle, 3000-2800cm-1Locate primary amine characteristic peak from scratch, illustrate successfully Modified SiO2Nano-particle.(d), (e), (f) are in 1730cm-1Place is absorbed as carbonyl absorption on PLA and PDEAEMA chains, shows SiO2Nanoparticle surface hydroxyl successfully triggers DL- lactide open loops, and ATRP initiators successfully trigger DEAEMA to polymerize, and obtain With pH response SNP-g-PLA-b-cPDEAEMA1 polymer.
Fig. 3 is the thermal gravimetric analysis curve figure of (a) SNP, (b) SNP-g-PLA and (c) SNP-g-PLA-b-cPDEAEMA1.It is bent Line (a) is SiO2The thermogravimetric curve of nano-particle (SNP), when temperature rises to 800 DEG C from room temperature, it loses weight and is 9.4%, the predominantly dehydration between the water and silanol of silicon ball surface absorption.Curve (b) is the SiO of PLA grafting2Nano-particle (SNP-g-PLA) thermogravimetric curve, loses 9.2% weight more relative to curve (a), shows that PLA is successfully grafted to SiO2 Nanoparticle surface.Curve (c) is the SiO of the crosslinked polymer overmold of outer layer2Nano-particle (SNP-g-PLA-b- CPDEAEMA1 thermogravimetric curve), 6.7% weight is lost relative to curve (b) more, shows to successfully synthesize outer layer crosslinking SNP-g-PLA-b-cPDEAEMA1 polymer.
Fig. 4 is (a) SNP, (b) SNP-g-PLA, (c) SNP-g-PLA-b-cPDEAEMA1 and (d) pH responsive polymers The scanning electron microscope (SEM) photograph of base Janus hollow nanospheres PLA-b-cPDEAEMA1.(a) it is SiO2Nano-particle, passes throughMethod is closed Into Nano particles of silicon dioxide size it is homogeneous, surface is smooth.(b) it is the SiO of PLA grafting2Nano-particle (SNP-g-PLA), Can significantly it be found out by (b), silicon ball surface becomes coarse, shows that PLA is successfully grafted to its surface.(c) it is crosslinked for outer layer The SiO of polymer overmold2Nano-particle (SNP-g-PLA-b-cPDEAEMA1), silicon ball surface is more coarse, and than more uniform, Show to trigger monomer polymerization and using EGDMA as crosslinking agent by ATRP initiators, it is crosslinked with pH sound to be successfully prepared outer layer The SNP-g-PLA-b-cPDEAEMA1 polymer of answering property.(d) for SNP-g-PLA-b-cPDEAEMA1 after hf etching, The obtained polymer matrix Janus hollow nanospheres PLA-b-cPDEAEMA1 with pH responses.It can be seen that carved through hydrofluoric acid After erosion, the hollow ball partial collapse of formation, has certain thickness, hollow cavity body structure is still presented.
Fig. 5 is (a) SNP, (b) SNP-g-PLA, (c) SNP-g-PLA-b-cPDEAEMA1 and (d) pH responsive polymers The transmission electron microscope picture of base Janus hollow nanospheres PLA-b-cPDEAEMA1.(a) it is SiO2Nano-particle, size is homogeneous, edge Smooth, (b) is grafted SiO for PLA2Nano-particle (SNP-g-PLA), can significantly be found out by (b), silicon ball edge roughness, table Bright PLA is successfully connected to silicon ball surface.(c) it is the SiO of the crosslinked polymer overmold of outer layer2Nano-particle (SNP-g-PLA-b- CPDEAEMA), from figure it will be seen that the polymeric layer of silicon ball surface cladding is obviously thickened, and than more uniform, show to hand over The PDEAEMA of connection successfully coats silicon ball.(d) for SNP-g-PLA-b-cPDEAEMA1 after hf etching, obtain Polymer matrix Janus hollow nanosphere PLA-b-cPDEAEMA1 with pH responses, partial collapse, its cavity diameter is about 400nm。
The preparation of 2 pH responsive polymer base Janus hollow nanospheres PLA-b-cPDEAEMA2 of embodiment
(1) synthesis of SNP-OH：With embodiment 1.
(2) synthesis of SNP-g-PLA：With embodiment 1.
(3) synthesis of SNP-g-PLA-Br：With embodiment 1.
(4) preparation of SNP-g-PLA-b-cPDEAEMA2
0.05g SNP-g-PLA-Br are weighed in 50mL polymerization pipes, add 6mL anhydrous DMFs, 0.5g DEAEMA, 0.11g EGDMA、0.036g Me6TREN, ultrasound add liquid nitrogen frozen, vacuumize, melt completely to scattered, and repeated freezing-vacuumize- The circulation of thawing is three times.Then, 0.042g CuBr are added, then freeze-vacuumize-thaw cycle once, vacuumizing shape Tube sealing under state, when 70 DEG C of reactions 24 are small.After reaction, system is opened wide, terminates polymerization.Reaction mixture is centrifuged, in removing Clear liquid, solid are washed three times with THF, and SNP-g-PLA-b-cPDEAEMA2 is obtained when vacuum drying 24 is small at 50 DEG C.Product passes through SEM, TEM, TGA etc. confirm.
(5) preparation of pH responsive polymers base Janus hollow nanospheres PLA-b-cPDEAEMA2：With embodiment 1.
The preparation of 3 pH responsive polymer base Janus hollow nanospheres PLA-b-cPDEAEMA3 of embodiment.
(1) synthesis of SNP-OH：With embodiment 1.
(2) synthesis of SNP-g-PLA：With embodiment 1.
(3) synthesis of SNP-g-PLA-Br：With embodiment 1.
(4) preparation of SNP-g-PLA-b-cPDEAEMA3
0.05g SNP-g-PLA-Br are weighed in 50mL polymerization pipes, add 6mL anhydrous DMFs, 0.8g DEAEMA, 0.11g EGDMA、0.045g Me6TREN, ultrasound add liquid nitrogen frozen, vacuumize, melt completely to scattered, and repeated freezing-vacuumize- The circulation of thawing is three times.Then, 0.028g CuBr are added, then freeze-vacuumize-thaw cycle once, vacuumize state Lower tube sealing, when 70 DEG C of reactions 24 are small.After reaction, system is opened wide, terminates polymerization.Reaction mixture is centrifuged, removes supernatant Liquid, solid are washed three times with THF, and SNP-g-PLA-b-cPDEAEMA3 is obtained when vacuum drying 24 is small at 50 DEG C.Product by SEM, TEM, TGA etc. confirm.
(5) preparation of pH responsive polymers base Janus hollow nanospheres PLA-b-cPDEAEMA2：With embodiment 1.
From the point of view of building-up process, using silica as template, the ring-opening polymerisation grafting PLA after amino, hydroxyl modification；Pass through again ATRP initiators are modified, and pass through PDEAEMA of the ATRP polymerization grafting with pH responses；Most etch to obtain with pH sound through HF afterwards The Janus hollow nanospheres of answering property.Scanning electron microscope and transmission electron microscope show that this method can obtain Janus hollow nanospheres, Illustrate the feasibility of the method.This Janus hollow nanospheres being made of PLA/PDEAEMA, since it is with pH responses Property, biological degradability and good biocompatibility, have good application prospect in the field such as drug delivery and controlled release.

Claims (5)

  1. The preparation method of 1.pH responsive polymer base Janus hollow nanospheres, it is characterised in that the pH responses polymerization Thing base Janus hollow nanospheres are hollow structure, and internal layer is hydrophobic degradable polylactic acid, and outer layer is with pH responses Crosslinked polymethylacrylic acid lignocaine ethyl ester, preparation method includes the following steps：
    1）Using Nano particles of silicon dioxide as template, hydroxy kind initiator is introduced on its surface, obtains intermediate 1；Specially：
    1.1）Ethanol, ammonium hydroxide and deionized water are added in single-necked flask, stirred evenly, then instills positive silicic acid tetrem dropwise The ethanol solution of ester, when 30-40 DEG C of reaction 10-15 is small under magnetic agitation, reaction mixture is centrifuged, removes supernatant liquor, receipts Collection white solid obtains Nano particles of silicon dioxide；
    1.2）Nano particles of silicon dioxide is added in ethanol, ultrasonic disperse, then adds gamma-aminopropyl-triethoxy silicon Alkane, N2 Under protection, when 60-80 DEG C of magnetic agitation reaction 40-50 is small, reaction mixture is centrifuged, removes supernatant liquor, is collected Solid obtains the Nano-meter SiO_2 of surface amino groups modification2Microballoon；
    1.3）The Nano-meter SiO_2 that surface amino groups are modified2Microballoon and dimethylbenzene mixing, ultrasonic disperse, add hydroxy kind initiator and shrink Glycerine, vacuumizes, and leads to nitrogen, under nitrogen protection, when 60-65 DEG C of reaction 18-24 is small, reaction mixture is centrifuged, in removing Clear liquid, collects solid and obtains intermediate 1；The Nano-meter SiO_2 that surface amino groups are modified2The mass ratio of microballoon and glycidol is：2: 0.8-1；
    2）By intermediate 1, DL- lactides and dimethylformamide in container, ultrasonic disperse, is added dropwise stannous octoate, vacuumizes, Logical nitrogen, under nitrogen protection, when 125-130 DEG C of reaction 45-50 is small, obtains intermediate 2；
    3）By intermediate 2 and CH2Cl2Mixing, ultrasonic disperse, adds triethylamine and ɑ-bromo isobutyl acylbromide, frozen water under ice-water bath When reaction 1-2 is small in bath, then when room temperature reaction 45-50 is small, reaction mixture is centrifuged, removes supernatant, collects solid Obtain intermediate 3；
    4）By intermediate 3, diethylaminoethyl methacrylate, ethylene glycol dimethacrylate, three（2- dimethylamino second Base）Amine is mixed with dimethylformamide, ultrasonic disperse, is added liquid nitrogen frozen, is vacuumized, and is melted；CuBr is added, adds liquid nitrogen Freezing, vacuumizes, and melts；Then the tube sealing under the state that vacuumizes, 70-75 DEG C reaction 18-24 it is small when, by reaction mixture from The heart, remove supernatant, collects solid and obtains intermediate 4；
    5）Intermediate 4 is used into hf etching at room temperature, obtains target product.
  2. 2. the preparation method of pH responsive polymers base Janus hollow nanospheres according to claim 1, its feature exist In：The mass ratio of intermediate 1 and DL- lactides is：1:14-16.
  3. 3. the preparation method of pH responsive polymers base Janus hollow nanospheres according to claim 1, its feature exist In：Step 3）In, the mass ratio of intermediate 2 and ɑ-bromo isobutyl acylbromide is：1:16-20.
  4. 4. the preparation method of pH responsive polymers base Janus hollow nanospheres according to claim 1, its feature exist In：Step 4）In, intermediate 3 and the mass ratio of diethylaminoethyl methacrylate are：1:14-16；Methacrylic acid diethyl The molar ratio of amino ethyl ester and ethylene glycol dimethacrylate is：8-10:1.
  5. 5. the preparation method of pH responsive polymers base Janus hollow nanospheres according to claim 1, its feature exist In：The concentration expressed in percentage by volume of hydrofluoric acid is 10%-50%.
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