Summary of the invention
The objective of the invention is to provide a kind of propylene glycol amine derivative cationic-liposome nano-particle and preparation method thereof, can realize nucleic acid drug transhipment in the born of the same parents outside born of the same parents in the hope of this propylene glycol amine derivative cationic-liposome nano-particle.
Propylene glycol amine derivative cationic-liposome nano-particle of the present invention is iodate 2,3-dialkoxy-1-(
N,
N,
N-trimethyl) third ammonium or bromination 2,3-dialkoxy-1-(
N,
N-dimethyl-
N-(2-ethoxy)) third ammonium, said alkoxyl is n-octyl, dodecyl, n-tetradecane base, n-hexadecyl, AI3-06523 base.
The method for preparing of said propylene glycol amine derivative cationic-liposome nano-particle comprises the steps:
(1) with the epoxychloropropane being raw material, is catalyst with a hydration p-methyl benzenesulfonic acid, and water is solvent and reactant, and the back hydrolysis open loop obtains colourless liquid 3-chloro-1,2-propylene glycol through column chromatographic isolation and purification;
(2) in the presence of sodium hydroxide, the colourless liquid 3-chloro-1 that step (1) is obtained, the 2-propylene glycol with
N,
N-dimethylamine hydrochloride carries out the tertiary amine reaction, through column chromatographic isolation and purification handle obtain yellow liquid 3-(
N,
N-dimethyl amido)-1,2-propylene glycol;
(3) being solvent with the oxolane, is catalyst with the sodium hydride, 3-(
N,
N-dimethyl amido)-1,2-propylene glycol and alkyl bromide back flow reaction obtain 2 through the column chromatographic isolation and purification processing, 3-dialkoxy-1-(
N,
N-dimethyl) propylamine;
(4) step (3) obtain 2,3-dialkoxy-1-(
N,
N-dimethyl) propylamine and iodomethane carry out quaternary ammonium salinization reaction, get white solid through the re-crystallizing in ethyl acetate purification process, after the supersonic oscillations aqueous dispersion, obtain corresponding propylene glycol amine derivative cationic-liposome TMA-Apd nano-particle.
The method for preparing of said propylene glycol amine derivative cationic-liposome nano-particle is characterized in that this method for preparing comprises the steps:
(1) with the epoxychloropropane being raw material, is catalyst with a hydration p-methyl benzenesulfonic acid, and water is solvent and reactant, and the back hydrolysis open loop obtains colourless liquid 3-chloro-1,2-propylene glycol through column chromatographic isolation and purification;
(2) in the presence of sodium hydroxide, the colourless liquid 3-chloro-1 that step (1) is obtained, the 2-propylene glycol with
N,
N-dimethylamine hydrochloride carries out the tertiary amine reaction, through column chromatographic isolation and purification handle obtain yellow liquid 3-(
N,
N-dimethyl amido)-1,2-propylene glycol;
(3) being solvent with the oxolane, is catalyst with the sodium hydride, 3-(
N,
N-dimethyl amido)-1,2-propylene glycol and alkyl bromide back flow reaction obtain 2 through the column chromatographic isolation and purification processing, 3-dialkoxy-1-(
N,
N-dimethyl) propylamine;
(4) step (3) obtain 2,3-dialkoxy-1-(
N,
N-dimethyl) propylamine and 1-bromoethanol carry out quaternary ammonium salinization reaction, get white solid through the re-crystallizing in ethyl acetate purification process, after the supersonic oscillations aqueous dispersion, obtain propylene glycol amine derivative cationic-liposome HEDMA-Apd nano-particle.
The rate of charge of said step (1) is the epoxychloropropane of mol ratio 1:0.002:4.3: a hydration p-methyl benzenesulfonic acid: water; 100 ℃ of back flow reaction 6h concentrate, and the column chromatography for separation eluant is the petroleum ether of volume ratio 2:1: ethyl acetate makes 3-chloro-1, the 2-propylene glycol.
The rate of charge of said step (2) is the 3-chloro-1 of mol ratio 1:5.5:5.5,2-propylene glycol: dimethylamine hydrochloride: sodium hydroxide; Stirring at normal temperature reaction 12h, the column chromatography for separation eluant is the ethyl acetate of volume ratio 10:1: methanol, purification obtain yellow liquid 3-(
N,
N-dimethyl amido)-1,2-propylene glycol.
The rate of charge of said step (3) be mol ratio 1:2:4 3-(
N,
N-dimethyl amido)-1,2-propylene glycol: sodium hydride: alkyl bromide; With the oxolane is solvent, 65
oC 24 h that reflux, the column chromatography for separation eluant is the ethyl acetate of volume ratio 1:1: petroleum ether, yellow liquid 2,3-dialkoxy-1-(
N,
N-dimethyl) propylamine, said alkyl bromide are n-Octyl Bromide, dodecyl bromide, n-tetradecane base bromine, n-hexadecyl bromine, AI3-06523 base bromine.
The rate of charge of said step (4) is 2 of mol ratio 1:10,3-dialkoxy-1-(
N,
N-dimethyl) propylamine: iodomethane; With the acetonitrile is solvent, and 81 ℃ of backflow 15h get white solid iodate 2 through re-crystallizing in ethyl acetate, 3-dialkoxy-1-(
N,
N,
N-trimethyl) third ammonium obtains cationic-liposome TMA-Apd nano-particle after the supersonic oscillations aqueous dispersion.
The rate of charge of said step (4) is 2 of mol ratio 1:5,3-dialkoxy-1-(
N,
N-dimethyl) propylamine: 1-bromoethanol; With the acetonitrile is solvent, and 81 ℃ of backflow 12h get white solid bromination 2 through re-crystallizing in ethyl acetate, 3-dialkoxy-1-(
N,
N-dimethyl-
N-(2-ethoxy)) third ammonium obtains cationic-liposome HEDMA-Apd nano-particle after the supersonic oscillations aqueous dispersion.
Said acetonitrile consumption is: 1g2,3-dialkoxy-1-(
N,
N-dimethyl) propylamine uses the 20ml acetonitrile, and not enough 1g is by 1g.
Major advantage propylene glycol amine derivative cationic-liposome nano-particle of the present invention has advantages such as structural stability is good, size is moderate, narrow diameter distribution, surface charge is moderate, preparation cost is cheap, can satisfy the basic demand that the DNA transport vehicle should possess.And cost of material is cheap, synthetic operation is simple and easy, the propylene glycol amine derivative cationic-liposome of ability efficient production different structure.Various cationic-liposomes are behind the water ultra-sonic dispersion, and the mean diameter of gained cationic-liposome nano-particle, PDI distribution, Zeta surface potential and pH value are seen table 1.Data show in the table, and the mean diameter of gained cationic-liposome nano-particle is 60-220nm; The PDI value is little, and particle size distribution is concentrated relatively; Most cationic-liposome nano-particle have higher surface potential (40-60 mv) and moderate pH value.Above-mentioned each physical parameter shows that the aminoacid cationic-liposome nano-particle of gained has the potentiality through electrostatic interaction combination and transporter gene class medicine.
The mean diameter of cationic-liposome, PDI distribution, Zeta surface potential and pH value after table 1 aqueous dispersion
The specific embodiment
Further set forth content of the present invention below in conjunction with embodiment, the code name of each propylene glycol amine derivative cationic-liposome is listed in table 2 respectively with corresponding chemical constitution.The mean diameter of cationic-liposome, PDI distribution, Zeta surface potential and pH value are listed in table 2 after each propylene glycol amine derivative cationic-liposome aqueous dispersion.
The preparation of embodiment 1. propylene glycol amine derivative cationic-liposome TMA-Apd-C12 nano-particle:
In 100 mL round-bottomed flasks, add epoxychloropropane (23.6 g, 260.0 mmol), a hydration p-methyl benzenesulfonic acid (0.10 g, 0.58 mmol) and water (20 mL) successively, back flow reaction.TLC (petroleum ether: ethyl acetate=1:1) detects, react 6 h after, react no significant change, stopped reaction is cooled to room temperature, reactant liquor becomes glassy yellow, and is concentrated.Through column chromatography (eluant: petroleum ether: ethyl acetate=2: 1) separate, get colourless liquid 3-chloro-1, the 2-propylene glycol
In 50 mL round-bottomed flasks, add 3-chloro-1,2-propylene glycol (2.6 g, 24.0 mmol) and water (15 mL).Reaction mixture is cooled to 0 ° of C with ice-water bath, stirs slowly to add sodium hydroxide (5.0 g, 120.0 mmol) down.After finishing, after the question response mixeding liquid temperature rises to room temperature, remove ice-water bath.Add dimethylamine hydrochloride (10.0 g, 123.4 mmol), use rubber stopper seal, stirring at normal temperature 12 h.(ethyl acetate: methanol=5: 1) detect, the raw material fundamental reaction is complete for TLC.In reaction system, add water (10 mL), with chloroform (40 mL/ time) extraction 3 times, merge organic facies, organic facies use anhydrous sodium sulfate drying, filters, and is concentrated.Residue through column chromatography (eluant: ethyl acetate: methanol=10: 1) separate, yellow liquid 3-(
N,
N-dimethyl amido)-1,2-propylene glycol
In 50 mL round-bottomed flasks, add
N,
N-dimethyl amido-1,2-propylene glycol (2.0 g, 17.0 mmol) and oxolane (20 mL).Reaction mixture is cooled to 0 ° of C with ice-water bath, stirs down slowly to add sodium hydride (1.6 g, 68.0 mmol) in batches, and after finishing, the question response mixeding liquid temperature rises to room temperature, removes ice-water bath.Slowly drip dodecyl bromide (8.5 g, 34.0 mmol), 24 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, water and ethyl acetate extraction, organic facies is used anhydrous sodium sulfate drying, filters, and concentrates.Residue through column chromatography (eluant: petroleum ether: ethyl acetate=1: 1) separate, glassy yellow liquid 2,3-two n-dodecane Oxy-1s-(
N,
N-dimethyl) propylamine
In 50 mL round-bottomed flasks, add 2,3-two n-dodecane Oxy-1s-(
N,
N-dimethyl) propylamine (1.0 g, 2.2 mmol) and acetonitrile (20 mL).Stir down and drip iodomethane (3.1 g, 21.8 mmol), 15 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, get yellow solid, use acetic acid ethyl dissolution, be cooled to room temperature, the adularescent solid is separated out, and filters, and gets white solid iodate 2,3-two n-dodecane Oxy-1s-(
N,
N,
N-trimethyl) third ammonium
Get iodate 2,3-two n-dodecane Oxy-1s-(
N,
N,
N-trimethyl) third ammonium (6.0 mg, 0.01 mmol), (10 mL) gets cationic-liposome TMA-Apd-C12 nano-particle through ultrasonic dispersing with redistilled water; Record mean diameter 60.64 nm with Zetasizer Nano ZS appearance; PDI distributes 0.426, surface potential+53.4 mv, pH=5.8.
The preparation of embodiment 2. propylene glycol amine derivative cationic-liposome HEDMA-Apd-C12 nano-particle:
In 50 mL round-bottomed flasks, add 2,3-two n-dodecane Oxy-1s-(
N,
N-dimethyl) propylamine (0.3 g, 0.7 mmol) and acetonitrile (20 mL) stir dripping bromine ethanol (0.4 g, 3.5 mmol) down, and 12 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, get yellow solid, use acetic acid ethyl dissolution, be cooled to room temperature, the adularescent solid is separated out, and filters, and gets white solid bromination 2,3-two n-dodecane Oxy-1s-(
N,
N-dimethyl-
N-(2-ethoxy)) third ammonium
Get bromination 2,3-two n-dodecane Oxy-1s-(
N,
N-dimethyl-
N-(2-ethoxy)) third ammonium (5.8 mg; 0.01 mmol); (10 mL) gets cationic-liposome HEDMA-Apd-C12 nano-particle through ultrasonic dispersing with redistilled water, records mean diameter 97.88 nm with Zetasizer Nano ZS appearance, and PDI distributes 0.360; Surface potential+49.9 mv, pH=5.4.
The preparation of embodiment 3. propylene glycol amine derivative cationic-liposome TMA-Apd-C8 nano-particle:
In 50 mL round-bottomed flasks, add
N,
N-dimethyl amido-1,2-propylene glycol (2.3 g, 20.4 mmol) and oxolane (40 mL).Reaction mixture is cooled to 0 ° of C with ice-water bath, stirs down slowly to add sodium hydride (2.0 g, 81.6 mmol) in batches, and after finishing, the question response mixeding liquid temperature rises to room temperature, removes ice-water bath.Slowly drip normal octane base bromine (7.9 g, 40.8 mmol), 24 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, water and ethyl acetate extraction, organic facies is used anhydrous sodium sulfate drying, filters, and concentrates.Residue through column chromatography (eluant: petroleum ether: ethyl acetate=1: 1) separate, glassy yellow liquid 2,3-two normal octane Oxy-1s-(
N,
N-dimethyl) propylamine
In 50 mL round-bottomed flasks, add 2,3-two normal octane Oxy-1s-(
N,
N-dimethyl) propylamine (1.1 g, 3.2 mmol) and acetonitrile (20 mL).Stir down and drip iodomethane (4.5 g, 32.0 mmol), 15 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, get crocus liquid.Through column chromatography (eluant: ethyl acetate: methanol=5: 1) separate, white solid iodate 2,3-two normal octane Oxy-1s-(
N,
N,
N-trimethyl) third ammonium
Get iodate 2,3-two normal octane Oxy-1s-(
N,
N,
N-trimethyl) third ammonium (4.9 mg, 0.01 mmol), (10 mL) gets cationic-liposome TMA-Apd-C8 nano-particle through ultrasonic dispersing with redistilled water; Record mean diameter 105.1 nm with Zetasizer Nano ZS appearance; PDI distributes 0.416, surface potential+51.3 mv, pH=5.4.
The preparation of embodiment 4. propylene glycol amine derivative cationic-liposome HEDMA-Apd-C8 nano-particle:
In 50 mL round-bottomed flasks, add 2,3-two normal octane Oxy-1s-(
N,
N-dimethyl) propylamine (1.1 g, 3.2 mmol) and acetonitrile (20 mL) stir dripping bromine ethanol (2.0 g, 16.0 mmol) down, and 12 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, get yellowish-brown liquid.Through column chromatography (eluant: ethyl acetate: methanol=2: 1) separate, white solid bromination 2,3-two normal octane Oxy-1s-(
N,
N-dimethyl-
N-(2-ethoxy)) third ammonium
Get bromination 2,3-two normal octane Oxy-1s-(
N,
N-dimethyl-
N-(2-ethoxy)) third ammonium (4.7 mg; 0.01 mmol); (10 mL) gets cationic-liposome HEDMA-Apd-C8 nano-particle through ultrasonic dispersing with redistilled water, records mean diameter 162.6 nm with Zetasizer Nano ZS appearance, and PDI distributes 0.456; Surface potential+57.4 mv, pH=5.4.
The preparation of embodiment 5. propylene glycol amine derivative cationic-liposome TMA-Apd-C14 nano-particle:
In 50 mL round-bottomed flasks, add
N,
N-dimethyl amido-1,2-propylene glycol (1.8 g, 15.9 mmol) and oxolane (20 mL).Reaction mixture is cooled to 0 ° of C with ice-water bath, stirs down slowly to add sodium hydride (1.5 g, 63.6 mmol) in batches, and after finishing, the question response mixeding liquid temperature rises to room temperature, removes ice-water bath.Slowly drip n-tetradecane base bromine (8.8 g, 31.8 mmol), 24 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, water and ethyl acetate extraction, organic facies is used anhydrous sodium sulfate drying, filters, and concentrates.Residue through column chromatography (eluant: petroleum ether: ethyl acetate=1: 1) separate, faint yellow solid 2,3-two n-tetradecane Oxy-1s-(
N,
N-dimethyl) propylamine
In 50 mL round-bottomed flasks, add 2,3-two n-tetradecane Oxy-1s-(
N,
N-dimethyl) propylamine (0.8g, 1.7 mmol) and acetonitrile (20 mL).Stir down and drip iodomethane (2.4 g, 17.0 mmol), 15 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, get yellow solid, use acetic acid ethyl dissolution, be cooled to room temperature, the adularescent solid is separated out, and filters, and gets white solid iodate 2,3-two n-tetradecane Oxy-1s-(
N,
N,
N-trimethyl) third ammonium
Get iodate 2,3-two n-tetradecane Oxy-1s-(
N,
N,
N-trimethyl) third ammonium (6.5 mg, 0.01 mmol), (10 mL) gets cationic-liposome TMA-Apd-C14 nano-particle through ultrasonic dispersing with redistilled water; Record mean diameter 82.26 nm with Zetasizer Nano ZS appearance; PDI distributes 0.392, surface potential+46.7 mv, pH=5.4.
The preparation of embodiment 6. propylene glycol amine derivative cationic-liposome HEDMA-Apd-C14 nano-particle:
In 50 mL round-bottomed flasks, add 2,3-two n-tetradecane Oxy-1s-(
N,
N-dimethyl) propylamine (1.0 g, 1.9 mmol) and acetonitrile (20 mL) stir dripping bromine ethanol (1.2 g, 9.5 mmol) down, and 12 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, get yellow solid, use acetic acid ethyl dissolution, be cooled to room temperature, the adularescent solid is separated out, and filters, and gets white solid bromination 2,3-two n-tetradecane Oxy-1s-(
N,
N-dimethyl-
N-(2-ethoxy)) third ammonium
Get bromination 2,3-two n-tetradecane Oxy-1s-(
N,
N-dimethyl-
N-(2-ethoxy)) third ammonium (6.4 mg; 0.01 mmol); (10 mL) gets cationic-liposome HEDMA-Apd-C14 nano-particle through ultrasonic dispersing with redistilled water, records mean diameter 137.4 nm with Zetasizer Nano ZS appearance, and PDI distributes 0.397; Surface potential+44.6 mv, pH=5.8.
The preparation of embodiment 7. propylene glycol amine derivative cationic-liposome TMA-Apd-C16 nano-particle:
In 50 mL round-bottomed flasks, add
N,
N-dimethyl amido-1,2-propylene glycol (1.9 g, 16.8 mmol) and oxolane (20 mL).Reaction mixture is cooled to 0 ° of C with ice-water bath, stirs down slowly to add sodium hydride (1.6 g, 67.2 mmol) in batches, and after finishing, the question response mixeding liquid temperature rises to room temperature, removes ice-water bath.Slowly drip n-hexadecyl bromine (10.3 g, 33.6 mmol), 24 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, water and ethyl acetate extraction, organic facies is used anhydrous sodium sulfate drying, filters, and concentrates.Residue through column chromatography (eluant: petroleum ether: ethyl acetate=1: 1) separate, white solid 2,3-two hexadecane Oxy-1s-(
N,
N-dimethyl) propylamine
In 50 mL round-bottomed flasks, add 2,3-two hexadecane Oxy-1s-(
N,
N-dimethyl) propylamine (0.7 g, 1.2 mmol) and acetonitrile (20 mL).Stir down and drip iodomethane (1.7 g, 12 mmol), 15 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, get yellow solid, use acetic acid ethyl dissolution, be cooled to room temperature, the adularescent solid is separated out, and filters, and gets white solid iodate 2,3-two hexadecane Oxy-1s-(
N,
N,
N-trimethyl) third ammonium
Get iodate 2,3-two hexadecane Oxy-1s-(
N,
N,
N-trimethyl) third ammonium (7.1 mg, 0.01 mmol), (10 mL) gets cationic-liposome TMA-Apd-C16 nano-particle through ultrasonic dispersing with redistilled water; Record mean diameter 227.1 nm with Zetasizer Nano ZS appearance; PDI distributes 0.277, surface potential+42.4 mv, pH=5.8.
The preparation of embodiment 8. propylene glycol amine derivative cationic-liposome HEDMA-Apd-C16 nano-particle:
In 50 mL round-bottomed flasks, add 2,3-two hexadecane Oxy-1s-(
N,
N-dimethyl) propylamine (0.9 g, 1.6 mmol) and acetonitrile (20 mL) stir dripping bromine ethanol (1.0 g, 8.0 mmol) down, and 12 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, get yellow solid, use acetic acid ethyl dissolution, be cooled to room temperature, the adularescent solid is separated out, and filters, and gets white solid bromination 2,3-two hexadecane Oxy-1s-(
N,
N-dimethyl-
N-(2-ethoxy)) third ammonium
Get bromination 2,3-two hexadecane Oxy-1s-(
N,
N-dimethyl-
N-(2-ethoxy)) third ammonium (6.9 mg; 0.01 mmol); (10 mL) gets cationic-liposome HEDMA-Apd-C16 nano-particle through ultrasonic dispersing with redistilled water, records mean diameter 203.5 nm with Zetasizer Nano ZS appearance, and PDI distributes 0.411; Surface potential+51.8 mv, pH=5.4.
The preparation of embodiment 9. propylene glycol amine derivative cationic-liposome TMA-Apd-C18 nano-particle:
In 50 mL round-bottomed flasks, add
N,
N-dimethyl amido-1,2-propylene glycol (2.8 g, 24.8 mmol) and oxolane (50 mL).Reaction mixture is cooled to 0 ° of C with ice-water bath, stirs down slowly to add sodium hydride (2.4 g, 99.2 mmol) in batches, and after finishing, the question response mixeding liquid temperature rises to room temperature, removes ice-water bath.Slowly drip AI3-06523 base bromine (16.5 g, 49.6 mmol), 24 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, water and ethyl acetate extraction, organic facies is used anhydrous sodium sulfate drying, filters, and concentrates.Residue through column chromatography (eluant: petroleum ether: ethyl acetate=1: 1) separate, white solid 2,3-two AI3-06523 Oxy-1s-(
N,
N-dimethyl) propylamine
In 50 mL round-bottomed flasks, add 2,3-two AI3-06523 Oxy-1s-(
N,
N-dimethyl) propylamine (0.9 g, 1.4 mmol) and acetonitrile (20 mL).Stir down and drip iodomethane (2.0 g, 14 mmol), 15 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, get yellow solid, use acetic acid ethyl dissolution, be cooled to room temperature, the adularescent solid is separated out, and filters, and gets white solid iodate 2,3-two AI3-06523 Oxy-1s-(
N,
N,
N-trimethyl) third ammonium
Get iodate 2,3-two AI3-06523 Oxy-1s-(
N,
N,
N-trimethyl) third ammonium (7.7 mg, 0.01 mmol), (10 mL) gets cationic-liposome TMA-Apd-C18 nano-particle through ultrasonic dispersing with redistilled water; Record mean diameter 170.6 nm with Zetasizer Nano ZS appearance; PDI distributes 0.398, surface potential+57.5 mv, pH=5.4.
The preparation of embodiment 10. propylene glycol amine derivative cationic-liposome HEDMA-Apd-C18 nano-particle:
In 50 mL round-bottomed flasks, add 2,3-two AI3-06523 Oxy-1s-(
N,
N-dimethyl) propylamine (0.8 g, 1.3 mmol) and acetonitrile (20 mL) stir dripping bromine ethanol (0.8 g, 6.5 mmol) down, and 12 h reflux.TLC (ethyl acetate) detects, and the raw material fundamental reaction is complete.Concentrate, get yellow solid, use acetic acid ethyl dissolution, be cooled to room temperature, the adularescent solid is separated out, and filters, and gets white solid bromination 2,3-two AI3-06523 Oxy-1s-(
N,
N-dimethyl-
N-(2-ethoxy)) third ammonium
Get bromination 2,3-two AI3-06523 Oxy-1s-(
N,
N-dimethyl-
N-(2-ethoxy)) third ammonium (7.5 mg; 0.01 mmol); (10 mL) gets cationic-liposome HEDMA-Apd-C18 nano-particle through ultrasonic dispersing with redistilled water, records mean diameter 215.9 nm with Zetasizer Nano ZS appearance, and PDI distributes 0.320; Surface potential+40.1 mv, pH=5.4.
The chemical constitution of the various cationic-liposomes of table 2