Luận văn thạc sĩ Công nghệ hóa học: Nghiên cứu tạo hệ phân tán Nano Rutin

TRƯỜNG ĐẠI HỌC BÁCH KHOA PHAN THỊ MỸ TRANG NGHIÊN CỨU TẠO HỆ PHÂN TÁN NANO RUTIN Chuyên ngành: Công nghệ hóa học Mã số: 605275 LUẬN VĂN THẠC SĨ... +uQK ҦQK KѭӣQJ FӫD WӕF ÿӝ ÿӗQJ KyD

TRƯỜNG ĐẠI HỌC BÁCH KHOA

PHAN THỊ MỸ TRANG

NGHIÊN CỨU TẠO HỆ PHÂN TÁN NANO RUTIN

Chuyên ngành: Công nghệ hóa học Mã số: 605275

LUẬN VĂN THẠC SĨ

(Ghi rõ họ, tên, học hàm, học vị của Hội đồng chấm bảo vệ luận văn thạc sĩ) 1 Nguyễn Công Hào

2 Nguyễn Thị Phương Phong 3 Phan Thanh Sơn Nam 4 Lê Thị Hồng Nhan 5 Lê Thành Dũng Xác nhận của Chủ tịch Hội đồng đánh giá LV và Trưởng Khoa quản lý chuyên ngành sau khi luận văn đã được sửa chữa (nếu có)

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ABSTRACT This thesis focused on researching dispersions of nano rutin with rutin concentration of above 1%, use ethanol and cosurfactant to dissolve and disperse rutin In general, the particle size and stability of rutin suspension were affected by several factors such as types of surfactants, stables, rutin concentration, homogenization time, homogenization rate and homogenizers In presence of sodium stealoyl lactylate (SSL), size and stability of the dispersions were better than those using Tween 20 and Tween 80 To increase stability of dispersions of rutin, PVA 0.1% was used as a stable In addition, the size of rutin particles was also improved by changing the conditions of homogenization: high speed homogenizer SY (5.9 Pm), household blender Phillips (1.879 Pm) Especially, this size was also dramatically reduced in case of combining household blender and high pressure homogenizer APV in 5 cycle (830 nm for rutin 1% and 860 nm for rutin 5%) or high speed ball mill (400 nm for rutin 1% and 995 nm for rutin 5%) From the results obtained demonstrate to improve the concentration of rutin in dispersions while maintaining nanoscale is positive and promising applications in the future

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2.3.5 Phân tích hình thái h̩t b̹ng TEM (Transmission Electron Microscope) 29

2.3.6 Phân tích c̭u trúc 29

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LDS: Laser Difraction Spectrometry DNA : Deoxyribo Nucleic Acid

EPO : Erythropoietin

GSH : Glutathione

HPMC : Hydroxyl propyl methyl cellulose HPMCAS : hydroxyl propyl methyl cellulose acetate succinate IAR : Immediate Asthmatic Reaction

LAR : Late-Phase Asthmatic Reaction

LD: Light dynamic MDA : Malondialdehyde MePEG-b-PDLLA: Methanol Poly ethylene glycol ± b ± Poly D, L-lactic acid MePEG-b-PLA: Methanol Poly ethylene glycol ± b ± Poly L-lactic acid MLP: Magnitude of laser pathway

MnSOD : Manganous superoxide dismutase PACA: Polyalkylcyanoacrylate

PCL: 3RO\İ-caprolactone PCS: Photon Correlation Spectroscopy PEG : Poly ethylene glycol

PI: Polydispersity

PLA : Poly L-lactic acid

PLGA: Poly lactic-co-glycolic acid

PVA : Poly vinyl acetate

PVP :Poly vinyl pyrrolidone

QU : Quercetin

ROS : Reactive oxygen species

SDS: Sodium dedecyl sulfat SSL:Sodium stearoyl lactylate

XRD: X-ray diffraction

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Tuy nhiên, FNJQJQKѭQKLӅXGѭӧFOLӋXFyQJXӗQJӕFWKLrQQKLrQNKiFYLӋFPӣUӝQJSKҥP YL ӭQJGөQJFӫDUXWLQEӏKҥQFKӃ vì rutin kém tan WURQJQѭӟFGүQÿӃQ NKҧQăQJKҩSWKөYjRFѫWKӇUҩWtW9uYұ\YҩQÿӅÿDQJÿѭӧFFiFQKjNKRDKӑFTXDQWkPOjOjPFiFKQjRÿӇUXWLQÿѭӧFKҩSWKөPӝWFiFKWӕWQKҩW0ӝWWURQJQKӳQJJLҧLpháp ÿѭӧFÿѭDUDOjOjPJLҧPNtFKWKѭӟFKҥWUXWLQ[XӕQJNtFKWKѭӟFQDQR

+ѭӟQJQJKLrQFӭXWҥRKӋSKkQWiQQDQRFӫDUXWLQYүQFzQPӟLPҿFKѭDFyQKLӅXF{QJWUuQKQJKLrQFӭXWUrQWKӃJLӟLFNJQJQKѭWURQJQѭӟFYӅOƭQKYӵFQj\ĈӅWjL³1JKLrQFӭXWҥRKӋSKkQWiQnano UXWLQ´ÿѭӧFÿһWUDYӟLPөFWLrXOjQJKLrQFӭXWҥR KӋ SKkQ WiQ QDQR FӫD UXWLQ WURQJ QѭӟF YӟL QӗQJ ÿӝ WUrQ  Yj ÿiQK JLi NKҧQăQJFNJQJQKѭÿһFWtQKFӫDKӋ.ӃWTXҧQJKLrQFӭXÿҥWÿѭӧFWURQJOXұQYăQQj\OjFѫVӣFKRQKӳQJSKҫQQJKLrQFӭXVkXKѫQUӝQJ KѫQOLrQTXDQÿӃQӭQJGөQJFӫDrutin

&+ѬѪ1*: 7Ә1*48$1

Trong FKѭѫQJ Qj\ WUuQK Ej\ PӝW FiFK WәQJ TXDQ YӅ UXWLQ F{QJ QJKӋ QDQRFNJQJQKѭNӻWKXұWÿӇWҥRWLQKWKӇQDQRWKXӕF 3KҫQÿҫXWUuQKEj\YӅFҩXWU~FQJXӗQJӕF WtQK FKҩW Oê KyD Yj KRҥW WtQK VLQK KӑF FӫD UXWLQ 3KҫQ NӃ WLӃS ÿӅ FұS ÿӃQ NӻWKXұWÿӇWҥRYұWOLӋXFҩXWU~FQDQRYjSKkQORҥLYұWOLӋXQDQR&XӕLFQJOjPӝWVӕNӃWTXҧÿҥWÿѭӧFFӫDQKӳQJQJKLrQFӭXWҥRWLQKWKӇQDQRUXWLQJҫQÿk\

1.1 *,Ӟ,7+,ӊ89ӄ587,1

5XWLQ Oj KӧS FKҩW JO\FRVLGH WKXӝF Kӑ IODYRQRLG có mùi cDP EDR JӗP quercetin WKXӝFQKyPIODYRQRQHYjSKҫQÿѭӡQJUXWLQRVH &K~QJÿѭӧFELӃWÿӃQQKѭquercetin-3-rutinoside hay sorphorin và Oj PӝW WURQJ QKӳQJ GѭӧF OLӋX thiên nhiên UҩWFyJLiWUӏFXQJFҩSQKLӅXKRҥWFKҩWFyOӧLFKRVӭFNKӓHQKѭYLWDPLQ3[1] Tên FӫDchúng ÿLWӯWrQFӫD5XWDJUDYHROHQVPӝWORҥLFk\FNJQJFKӭDFKҩWUXWLQ

Tên IUPAC: [(3,4,5-trihydroxy-6methyl-oxan-2-yl)oxymethyl]oxan-2-yl]oxy-chromen-7-one

2-(3,4-dihydroxyphenyl)-4,5-dihydroxy-3-[3,4,5-trihyd-roxy-6-Công WKӭF&27H30O16

Hình 1 1: Công thͱc c̭u t̩o cͯa Rutin

5XWLQ Fy KjP OѭӧQJ FDR trong lúa mì, trong cây hoa hòe 1KұW EҧQ Sophora

Japonica L.), WURQJ KRD FӫD OXӕQJ KRD ÿҫX [XkQ Forsythia intermedia) Yj KRD ÿҫX

[XkQ7UXQJTXӕF (F suspensa) [1]

Ӣ9LӋW1DPQJXӗQFKtQKFӫDUXWLQOjKRDKzHSophora Japonica L Chúng

ÿѭӧFWuPWKҩ\QKLӅXӣ7KiL%uQK+j%ҳF1DP+j+ҧL'ѭѫQJ+ҧLSKzQJ1JKӋAn, và Tây Nguyên

1.1.1 7tQKFKҩWYұWOê và KyDKӑF

RXWLQWLQKNKLӃWOjWLQKWKӇKuQKNLPPjXYjQJKD\YjQJFKDQK FyNKӕLOѭӧQJSKkQWӱJPRO5XWLQNK{QJPLYjFyWKӇWUӣQrQVұPPjXGѭӟLWiFGөQJFӫDiQKViQJ7KѭӡQJJһSGҥQJUXWLQQJұPSKkQWӱQѭӟF1yFyWKӇJLҧLSKyQJPӝWSKkQWӱQѭӟFNKLÿѭӧFVҩ\NK{YӟLDFLGVXOIXULFÿһFYjOѭӧQJQѭӟFFzQOҥLVӁÿѭӧFORҥLUDEҵQJFiFKJLDQKLӋWÿӃQo

&WURQJiSVXҩWFKkQNK{QJKD\ NKRҧQJ160o&ӣiSVXҩWP{LWUѭӡQJ

ĈLӇPQyQJFKҧ\ӣo

C [2], khi QKLӋWÿӝ OrQÿӃQo&UXWLQVӁKRjQWRjQEӏSKkQKӫ\ Rutin kém EӅQPjXGѭӟLWiFGөQJiQKViQJ'Rÿy, QyFҫQÿѭӧFEҧRTXҧQWURQJOӑWӕLӣQѫLWKRiQJNKtWUiQKWLӃS[~FWUӵFWLӃSYӟi ánh sáng

5XWLQtWWDQWURQJQѭӟF- 0.0125 JOӣQKLӋWÿӝSKzQJ) Tuy nhiên, nó WDQWӕWWURQJPHWKDQROYjHWKDQRO [3-4]

5XWLQGӉEӏWKӫ\SKkQÿӇKuQKWKjQKTXHUFHWLQ48 [5], khi ly trích rutin WӯPӝWVӕWKӵFYұWăQÿѭӧFPүXOX{QOX{QFKӭD48ӣQKLӅXWӍOӋ

Quercetin FNJQJOjPӝWFKҩWR[LKyDPҥQK, ÿѭӧFWuPWKҩ\QKLӅXWURQJFk\ăQÿѭӧFQKѭ rutin

7tQKFKҩWTXDQWUӑQJQKҩWFӫD48OjFKҩWWҥRPLGүQ[XҩWWӯWKӵFYұWÿһFELӋWOjPLWKѫP

Hình 1 2: Công thͱc c̭u t̩o cͯa quercetin

Tên IUPAC: 2-(3,4- dihydroxyphenyl)- 3,5,7- trihydroxy- 4H- one

b &K͙QJXQJWK˱

4XHUFHWLQVҧQSKҭPWKӫ\SKkQFӫDUXWLQFNJQJ ÿѭӧF[HPOjPӝWFKҩWFKӕQJung WKѭWӕWYuYDLWUzӭFFKӃTXiWUuQKKuQKWKjQKJӕFWӵGRNK{QJPRQJPXӕQWURng FѫWKӇ9ӟLNӃWTXҧÿyTXHUFHWLQQJăQFKһQQKӳQJWiFQKkQJk\QJX\KҥLÿӃQWӃEjR (ÿһFELӋWOj'1$) ± QJX\rQQKkQFKtQKGүQÿӃQѭQJWKѭ[7]

Rutin và quercetin FyNKҧQăQJEҧRYӋWӃEjR'1$FKӕQJOҥL+2O2 ± gây ra VӵSKiKXӹ'1$WURQJFiFWӃEjRXQJWKѭPiXFӫDQJѭӡL [8]

c Kháng viêm

+RҥWÿӝQJkháng viêm FӫDFKҩWIODYRQRLGÿѭӧFNKҧRViWWUrQFKXӝWVai trò FӫDUXWLQWURQJEөQJFKXӝW (PJNJQJj\ӭFFKӃFҧJLDLÿRҥQFҩSWtQKYjPmQWtQKFӫDPүXWKtQJKLӋPkháng YLrPQj\ÿһFELӋWOj ӣJLDLÿRҥQPmQWtQK[9]

d 7iFGͭQJE̫RY͏WK̵Q

5XWLQNK{QJFKӍFyWiFGөQJ kháng oxi hóa FKӕQJXQJWKѭ Yj NKiQJ YLrPmà còn có tác dөQJ ÿһF ELӋW WURQJ EҧR YӋ WKұQ 7Kӱ QJKLӋP WUѭӟF WUrQ FKXӝW YӟLrutin JNJLSFKRWKҩ\NKҧQăQJOjPJLҧPVӵUӕLORҥQFKӭFQăQJWKұQPӝWFiFKÿiQJNӇJLҧPPӭFPDORQGLDOGHK\GH0'$FDRYjSKөFKӗLKRҥWÿӝQJ0Q62'ÿmVX\\ӃXFNJQJQKѭ PӭF JOXWDWKLRQH(GSH)1KӳQJSKiWKLӋQQj\ FKRWKҩ\ ROS là QJX\rQQKkQWURQJVӵWKLӃXPiXFөFEӝFҩSPiXOҥLJk\WәQWKѭѫQJWKұQYjUXWLQFyWiFÿӝQJEҧR YӋWKұQEҵQJFiFKӭFFKӃ526 YjFiFKRҥWÿӝQJFKӕQJVӵR[\KyD[10]

e 7iFGͭQJW͙Wÿ͙LYͣLE͏QKWL͋Xÿ˱ͥQJ

0ӝWORҥWFiFFKҩWJӗPQѭӟFNKRiQJDFLGDVFRUELFYjUXWLQWK~Fÿҭ\VӵWăQJcarbohydUDWFKX\ӇQKyDOLSLGQkQJFDRKjP OѭӧQJSODVPDFӫDDFLGDVFRUELFOjPJLҧPVӵFҫQWKLӃWWURQJYLӋFVӱGөQJWKXӕFKҥÿѭӡQJKX\ӃW[11]

f &K͙QJVX\͍Q

1JKLrQFӭXWUrQFKXӝWODQJQKҥ\FҧPYӟLDOEXPLQWUӭQJ2$ÿѭӧFWKӱYӟLFKҩWDHURVROL]H-2$NӃWTXҧFKRWKҩ\UXWLQFyWiFGөQJWӕWWURQJYLӋFÿLӅXWUӏӣJLDL

ÿRҥQ WӭF WKӡL ,$5 Yj JLDL ÿRҥQ FXӕL /$5 FӫD EӋQK VX\ӉQ TXD Vӵ ӭF FKӃ JLҧLSKyQJ KLVWLPLQH 3/$ Yj (32 OjP JLҧP YLӋF QҥS QHXWURSKLO Yj HRVLQRSKLO YjRSKәL[12]

1.1.3 ӬQJGөQJWURQJGѭӧFSKҭP

1KӡQKӳQJKRҥWWtQKUҩWFyJLiWUӏWURQJGѭӧFSKҭPQrQWӯOkXUXWLQÿmÿѭӧFVӱGөQJUӝQJUmLWURQJdòng WKXӕFÿLӅXWUӏ 7UrQWKӏWUѭӡQJWKXӕFFKӭDGѭӧFFKҩWUXWLQUҩWÿDGҥQJWӗQWҥLӣGҥQJEӝWGҥQJQѭӟFGҥQJYLrQQDQJ«QKѭQJSKәELӃQKѫQFҧYүQOjGҥQJYLrQEDR SKLP1KӳQJORҥLWKXӕFFKӭDGѭӧFFKҩWUXWLQFyWKӇVӱGөQJÿӇWUӏEӋQKWUƭJLmQWƭQK PҥFKVX\ӉQWKұQ«

Hình 1 3: Ͱng dͭng cͯa rutin trong G˱ͫc pẖm

1.2 &Ð1*1*+ӊ1$12

1.2.1 VұWOLӋXQDQR

&{QJQJKӋQDQREҳWÿҫXSKiWWULӇQWURQJEDWKұSNӹTXDQKѭQJF{QJQJKӋPӟLQj\ÿmÿҥWÿѭӧFVӵFK~êQKLӅXFҧWURQJYjQJRjLQѭӟF6iQJNLӃQF{QJQJKӋQDQRTXӕFJLDÿm[iFÿӏQKF{QJQJKӋQDQROj³1JKLrQFӭXFiFFҩSÿӝQJX\rQWӱSKkQWӱVLrXSKkQWӱYӟLNtFKWKѭӟFNKRҧQJ± QPÿӇWuPKLӇXYjWҥRUDYұWOLӋXFNJQJQKѭQJKLrQFӭXQKӳQJÿһFWtQKWtQKFKҩWYұWOê- VLQKKӑFÿӝFÿiRFӫDORҥLYұWOLӋXFyFҩXWU~FQKӓQKѭYұ\´

+LӋQQD\FQJYӟLF{QJQJKӋQDQRFiFNӻWKXұWÿDQJÿѭӧFQJKLrQFӭXYjSKiWWULӇQÿӇFyWKӇJLҧP NtFKWKѭӟFFiFSKҫQWӱQJX\rQYұWOLӋX&{QJQJKӋQj\NK{QJFKӍiSGөQJFKRYұWOLӋXPjQJj\FjQJPӣUӝQJUDFiFOƭQKYӵF\WӃVLQKKӑFPӻSKҭPGѭӧFSKҭP«

1.2.2 3KkQORҥL

'ӵDWUrQNtFKWKѭӟFQDQRFyWKӇSKkQORҥLYұWOLӋXQDQROjPEDORҥL[13]: ¾ Vұt liӋu nano 0-D bao gӗm vұt liӋu mà cҧ ba NtFKWKѭӟFÿӅu là kích WKѭӟc nano Các hҥt nano, tinh thӇ nano và chҩt keo thuӝc lӟp này

¾ Vұt liӋu nano 1-D: khác vӟi loҥi 0-D, chúng có mӝWNtFKWKѭӟc không phҧLQDQRĈLӇn hình là ӕng nano, dây nano, sӧi và sӧi nano

¾ Vұt liӋu nano 2-D chӍ có mӝt kích thѭӟF Oj QDQR ÿk\ Oj QKӳng lӟp nano, chҩt phӫ bӅ mһt nano, nano phim Nhӳng loҥi vұt liӋu khác, không có kích WKѭӟFQDQRÿѭӧc gӑi là vұt liӋu nano 3-D

Chúng VӁ WUӣ WKjQK PӝW WURQJ QKӳQJ ORҥL FKtQK FӫD WKXӕF GѭӟL QKLӅX KuQKWKӭFQKѭYLrQQpQYLrQQDQJ« tù\WKHROӧLtFKFӫDWKXӕFUҳQ9uYұ\WURQJWjLOLӋXQj\FK~QJW{LFKӍWұSWUXQJYjRORҥLYұWOLӋXQDQRWKXӕF-'FiFKҥWQDQRWLQKWKӇ

Hình 1 4: tFKWK˱ͣc các lo̩i v̵t li͏XQDQR/OjNtFKWK˱ͣc không ph̫LNtFKWK˱ͣc nano) [13]

1.2.3 7tQKFKҩWFӫDYұWOLӋXQDQR

1KӡNӻWKXұWYj F{QJQJKӋOjPJLҧPNtFKWKѭӟFKҥWFyNtFKWKѭӟFQDQRVӣKӳXQKLӅXWtQKFKҩWOêKyDÿӝFÿiR9jFNJQJGRYұ\PjFK~QJOjÿӕLWѭӧQJUҩWSKKӧSFKRVӵSKiWWULӇQFӫDKӋGүQWUX\ӅQWKXӕF

a) Di͏n tích b͉ m̿t và s͙ phân t͵ cͯa b͉ m̿t lͣn[14-15]

9ӟLWLQKWKӇUҳQKuQKFҫXFyÿѭӡQJNtQK GGLӋQWtFKEӅPһWWUrQPӝWÿѫQYӏÿRGLӋQWtFK Sg là:

7KHRF{QJWKӭFWUrQGLӋQWtFKEӅPһWFӫDYұWOLӋXVӁ WăQJOrQPӝWFiFKÿiQJNӇNKLYұWOLӋXÿѭӧFÿѭD[XӕQJNtFKWKѭӟFQDQR

Hình 1 5: Sӵ WăQJÿiQJNӃ diӋn tích bӅ mһt nhӡ giҧm kích cӥ hҥt [15].

b) ĈL͋m nóng ch̫y

VұWOLӋXFyNtFKWKѭӟFQDQRVӁ FyÿLӇPQyQJFKҧ\WKҩS JLҧP[XӕQJPѭӡLKD\hàng WUăPÿӝ, WKҩS KѫQYұWOLӋXOӟQ[16]

c) Kh̫ QăQJSKkQWiQ͝Qÿ͓nh d̩ng huy͉n phù

HҥWFyNtFKWKѭӟc micro dӉ bӏ kӃt tө và sa lҳng do trӑng lӵc Tuy nhiên, hҥt FyNtFKWKѭӟc nano sӁ dӉ dàng giӳ ӣ trҥQJWKiLOѫOӳng và khҧ QăQJSKkQWiQәn ÿӏnh dҥng huyӅQSKWăQJOrQ Có hiӋQWѭӧng này là do nhӡ FyNtFKWKѭӟc hҥt nhӓ, lӵc hҩp dүn lên hҥt nano sӁ nhӓ KѫQUҩt nhiӅu so vӟi hҥt lӟn

Vұn tӕc lҳQJYWKHRÿӏnh luұt Stoke là:

7URQJÿy g OjJLDWӕFWUӑQJWUѭӡQJ ( 9.8 m/s)

U OjNKӕLOѭӧQJULrQJFKҩWOӓQJ (997 kg/m3 YӟLQѭӟFӣ 25oC) P1 ÿӝQKӟWFKҩWOӓQJ (0.00089 Pa/VYӟLQѭӟFӣ 25oC)

Bên cҥnh ÿy, chuyӇQÿӝng nhiӋt (Brownian) FNJQJJySSKҫn duy trì trҥng thái Oѫ Oӳng cӫa hҥt HҥW NtFK WKѭӟF Gѭӟi 1000 nm sӁ NK{QJ ÿӭQJ \rQ Yu ÿӍnh cӫa chuyӇQÿӝng nhiӋt lӟQKѫQQKLӅu sӭc kéo lӵc hҩp dүn Vì thӃ, hӋ phân tán nano sӁ không lҳng và bӅn vӳQJKѫQFK~QJ dӉ dàng giӳ ӣ trҥQJWKiLOѫOӳng vӟi mұWÿӝ lӟn [14]

d) Ĉ͡ tan bão hòa, tính tan cͯa v̵t li͏XWăQJOrQNKLÿ˱D[X͙QJNtFKWK˱ͣc nano

.KLKҥWÿѭӧFÿѭD[XӕQJ NtFKWKѭӟFGѭӟL 1 ± 2 Pm, ÿӝ WDQ EmR KzD Oj PӝWKjP SKө WKXӝF YjR NtFK WKѭӟF KҥW Ĉӝ WDQ EmR KzD WăQJ OrQ ÿiQJ NӇ NKL NtFKWKѭӟFKҥWQKӓKѫQ 1000 nm [15, 17] 6R YӟL YұW OLӋX Fy NtFK WKѭӟF PLFUR KәQKӧSKҥWQDQRQKѭӣWUҥQJWKiLVLrXEmRKzD

7tQKWDQFӫDYұW OLӋXFyNtFKWKѭӟFQDQRFNJQJWăQJOrQUҩWQKLӅXVRYӟLYұWOLӋXOӟQKuQK'RÿyWLQKWKӇQDQRWKXӕFOjJLҧLSKiSKLӋXTXҧÿӇWăQJÿӝtan bão hòaWăQJWtQKWDQFӫDGѭӧFOLӋX

Hình 1 6: Hi͏u qu̫ cͯDÿ˱ͥng kính h̩t r̷n trong thí dͭ gi̫ ÿ͓nh v͉ tính tan

(S: tính tan ͧ b͉ m̿t cͯa h̩t; So: tính tan bên trong) [17]

Hình 1 7: S͹ gi̫n kho̫ng cách khu͇FKWiQKYjQK˱WK͇ WăQJJUDGLHQWQ͛QJÿ͡ (cs-cx)/h

và cu͙i cùng tăQJ t͙Fÿ͡ hòa tan dc/dt = D.A (cs-cx)/h [15]

e) Hi͏u qu̫ trên s͹ v̵n chuy͋n sinh h͕c

Hҥt nano FyNtFKWKѭӟc phù hӧp vӟi NtFKWKѭӟc các khe hӣ, lӛ trên tӃ bào hay mô, nên chúng dӉ dàng di chuyӇQ YjR Fѫ WKӇ FRQ QJѭӡL Yj ÿѭӧc hҩp thө mӝt

cách dӉ dàng Chính vì thӃ, hҥt nano ÿyQJ YDLWUzUҩt quan trӑng trong sӵ phát triӇn hӋ dүn truyӅn thuӕc (uӕQJKD\WLrPWƭQKPҥch) [17]

1.2.4 .ӻWKXұWFѫEҧQFӫDF{QJQJKӋQDQR

&yQKLӅXSKѭѫQJSKiSÿӇWҥRUDYұWOLӋXQDQRWURQJÿyKDLQJX\rQOêFѫEҧQlà: Top-down và Bottom-XS 7ӯ KDL QJX\rQ Oê Qj\ Fy WKӇ WLӃQ KjQK EҵQJ QKLӅXSKѭѫQJSKiSF{QJQJKӋYjNӻWKXұWÿӇFKӃWҥRYұWOLӋXFҩXWU~FQDQR[18]

Hình 1 8: (A) nguyên lý Bottom-up và (B) nguyên lý Top-down

1.2.4.1 Bottom-up (³EXLOG-XS´)

Bottom-up là quá trình OҳSJKpSFiFKҥWFӥSKkQWӱKD\QJX\rQWӱOҥLÿӇWKX

ÿѭӧFNtFKWKѭӟFQDQR 4XiWUuQKQj\ÿLWӯFiFSKkQWӱÿѭӧFKzDWDQYjNӃWWӫDEҵQJFiFKWKD\ÿәLVӵSKkQFӵFFӫDGXQJP{LKRһFORҥLEӓduQJP{LQJD\OұSWӭF

3KѭѫQJ SKiS Qj\ UҩW NKy WKӵF KLӋQ Yu GӉ WҥR UD NtFK WKѭӟF PLFUR và dung P{LVӱGөQJÿҳWWLӅQĈӗQJWKӡL TXiWUuQKQj\OҥLSKөWKXӝFYjRÿӝWDQFӫDWKXӕFWURQJGXQJP{LYjGXQJP{LWDQWURQJQѭӟF 7ӯÿyYLӋFWKӵFKLӋQF{QJQJKӋQDQRWKHR SKѭѫQJ SKiS ERWWRP-XS Fy WKӇ WҥR UD FiF KuQK WKiL YұW OLӋX Fy ӭQJ GөQJ UҩWQKLӅXWURQJF{QJQJKLӋS

a 3K˱˯QJSKiSÿ͛QJN͇WWͯD

Hình 1 9: &˯FK͇KuQKWKjQKYjSKiWWUL͋QK̩WQDQRWURQJGXQJG͓FK

7URQJSKѭѫQJSKiSNӃWWӫDWӯGXQJGӏFKNKLQӗQJÿӝFӫDFKҩWÿҥWÿӃQPӝWWUҥQJWKiLEmRKzDWӟLKҥQWURQJGXQJGӏFKVӁ[XҩWKLӋQÿӝWQJӝWQKӳQJPҫPNӃWWө&iF PҫP NӃWWөÿyVӁSKiWWULӇQWK{QJTXD TXiWUuQK NKX\ӃFKWiQFӫD YұWFKҩWWӯGXQJGӏFKOrQEӅPһWFӫDFiFPҫPFKRÿӃQNKLPҫPWUӣWKjQKKҥWQDQRKuQK,) ĈӇ WKX ÿѭӧF KҥW Fy ÿӝ ÿӗQJ QKҩW FDR QJѭӡL WD FҫQ SKkQ WiFK KDL JLDL ÿRҥQ KuQKWKjQKPҫPYjSKiWWULӇQPҫP7URQJTXiWUuQKSKiWWULӇQPҫPFҫQKҥQFKӃVӵKuQK WKjQKFӫDQKӳQJPҫPPӟLCó nKӳQJSKѭѫQJSKiSNӃWWӫDWӯGXQJGӏFK QKѭ ÿӗQJNӃWWӫDQKNJWѭѫQJSRO\ROSKkQO\QKLӋW

b 9LQKNJW˱˯QJ

9LQKNJWѭѫQJPLFURHPXOVLRQOjPӝWWURQJQKӳQJSKѭѫQJSKiSÿѭӧFGQJNKiSKәELӃQÿӇWҥRKҥWQDQR9ӟLQKNJWѭѫQJ³QѭӟF-trong-GҫX´FiFJLӑWGXQJGӏFKQѭӟFEӏEү\EӣLFiFSKkQWӱFKҩWKRҥWKyDEӅPһWWURQJGҫXFiFPLFHOOHĈk\OjPӝWGXQJGӏFKӣWUҥQJWKiLFkQEҵQJQKLӋWÿӝQJWURQJVXӕWYjÿҷQJKѭӟQJ'RVӵJLӟLKҥQYӅNK{QJJLDQFӫDFiFSKkQWӱFKҩWKRҥWKyDEӅPһWVӵKuQKWKjQKYjSKiWWULӇQFiFKҥWQDQREӏKҥQFKӃWҥRQrQFiFKҥWQDQRUҩWÿӗQJQKҩW.tFKWKѭӟFKҥWFyWKӇWӯ- 1QPYӟLÿӝVDLNKiFNKRҧQJ- 0.3 nm

Hình 1 10: H͏ QKNJW˱˯QJQ˱ͣc trong d̯u và d̯XWURQJQ˱ͣc

3KѭѫQJSKiSQj\ÿmÿѭӧFWKӃJLӟLӭQJGөQJWӯOkXGRNKҧQăQJÿLӅXNKLӇQNtFKWKѭӟFKҥWGӉGjQJ&ѫFKӃFӫDSKҧQӭQJ[ҧ\UDWURQJKӋYLQKNJWѭѫQJOjSKҧQӭQJKyDKӑFWҥRFiFFKҩWPRQJPXӕQVӁ[ҧ\UDNKLWDKzDWUӝQFiFKӋYLQKNJWѭѫQJQj\OҥLYӟLQKDX

c 3K˱˯QJSKiSVLrXWͣLK̩Q

'RWKXӕFFySKkQWӱQKҽYjNK{QJSKkQFӵFQrQGQJ&22 VLrXWӟLKҥQOjPGXQJP{LKzDWDQWKXӕF.KL[ҧiSVXҩWÿӝWQJӝWYӅiSVXҩWNKtTX\ӇQ&22 VLrXWӟLKҥQ WKjQK NKt &22 FzQ WKXӕF VӁ NӃW WLQK 4Xi WUuQK JLҧP iS ÿѭӧF WKӵF KLӋQ UҩWnKDQK OѭӧQJ WKXӕF KzD WDQ WURQJ GXQJ P{L VӁ NӃW WLQK Yj SKkQ WiQ WUӣ OҥL P{LWUѭӡQJNK{QJGXQJP{LYӟLNtFKWKѭӟFQDQR

1.2.4.2 Top-down

Top - GRZQQJKƭDOjGQJQăQJOѭӧQJFDRÿӇFKLDQKӓPӝWKӋWKӕQJOӟQFXӕLFQJWҥRUDPӝWÿѫQYӏFyNtFKWKѭӟFQDQR3KѭѫQJSKiSQj\FKӫ\ӃXÿѭӧFVӱGөQJÿӇÿLӅXFKӃWKXӕFGҥQJWLQKWKӇQDQR

a 3K˱˯QJSKiSQJKL͉n

Trong má\QJKLӅQELKәQKӧSKӋKX\ӅQSKÿѭӧF[D\WUӝQYӟLFiFELQJKLӅQFy NtFK WKѭӟF Wӯ  -  ȝP %L QJKLӅQ Fy WKjQK SKҫQ EDR JӗP WKӫ\ WLQK PXӕL]LULFRQL=UJӕPKRһFQKӵDSRO\VW\UHQHOLrQNӃWQJDQJ

.tFKWKѭӟFVҧQSKҭPSKөWKXӝFYjRÿӝFӭQJ ÿӝGzQFӫDQJX\rQOLӋXYjELQJKLӅQ1JRjLUDOӵFQJKLӅQYjWKӡLJLDQQJKLӅQ FNJQJOj\ӃXWӕTX\ӃW ÿӏQKOӟQÿӃQNtFKWKѭӟFKҥW

b Ĉ͛ng hoá áp sṷt cao

&yKDLNӻWKXұWFѫEҧQVӱGөQJSKѭѫQJSKiSÿӗQJKRiiSVXҩWFDR - ĈӗQJKRiWURQJQѭӟF

- ĈӗQJKRiWURQJP{LWUѭӡQJNK{QJFyQѭӟFKRһFYӟLQѭӟFKRjWUӝQYӟLGXQJGӏFK

¾ ˰XÿL͋P

- 'ӉWҥRKҥWNtFKWKѭӟFQKӓ - KhônJJk\ăQPzQYұWOLӋX - ĈѭӧFӭQJGөQJWURQJÿLӅXFKӃWKXӕFFyÿӝKRjWDQNpPWURQJQѭӟFKD\WURQJFiFGXQJP{LKӳXFѫ

¾ 1K˱ͫFÿL͋P

- 7KLӃWEӏÿҳWWLӅQOjPWăQJJLiWKjQKVҧQ[XҩW

c 3K˱˯QJSKiSVLrXkP

&{QJQJKӋVLrXkPÿѭӧF[HPOjFyWiFGөQJQKѭTXiWUuQKÿӗQJQKҩWVӵQKNJKyDVӵSKkQWiQYjVӵQJKLӅQKҥWWURQJPӝWWKӡLJLDQGjL

7iFGөQJQJKLӅQKҥWVyQJVLrXkP[HQNӁWҥRUDFKXNǤiSVXҩWFDRYjFKXNǤiSVXҩWWKҩS7URQJFKXNǤiSVXҩWWKҩSFѭӡQJÿӝVyQJVLrXkPFDRWҥRUDFiFERQJEyQJFKkQNK{QJQKӓYj EӏEӇWURQJFKXNǤiSOӵFFDRWҥRUDVӵVӫLEӑWERQJEyQJ&iFKҥWNtFKWKѭӟFOӟQFyWKӇ[yLPzQEӅPһWGRVӵVӫLEӑWERQJEyQJWURQJFKҩWOӓQJ[XQJTXDQKYjJLҧPNtFKWKѭӟFKҥWGRYDFKҥPJLӳDFiFKҥWKRһFVӵVӫLEӑWKuQKWKjQKWUrQEӅPһW

6ӵQKNJ KyDVyQJVLrXVӁODQWӓDWURQJGXQJ GӏFKYjWҥRUDiSOӵFOӟQFKӫ\ӃX GR KLӋX ӭQJ VӫL EӑW ERQJ EyQJ Jk\ UD FiF FKҩW OӓQJ VӁ ÿѭӧF FKLD WKjQK FiFPҧQKYӥYj[HQNӁYӟLQKDX

&iF\ӃXWӕҧQKKѭӣQJÿӃQKLӋXTXҧVLrXkPFѭӡQJÿӝYjWҫQVӕVLrXkPWKӡLgian siêu âm

d K͇t hͫSSK˱˯QJSKiSN͇t tͭ YjSK˱˯QJSKiSÿ͛ng hóa

7URQJSKѭѫQJSKiSNӃWWөFiFKҥWWLQKWKӇVDXNKLNӃWWӫDFyWKӇWLӃSWөFSKiWWULӇQ NtFK WKѭӟF QӃX KӋ NK{QJ ÿӗQJ QKҩW ӃW KӧS YӟL SKѭѫQJ SKiS ÿӗQJ KyD ÿӇSKkQWiQÿӅXFiFKҥWWLQKWKӇNӃWWLQK WURQJGXQJGӏFKNӃWWLQK0һWNKiFNtFKWKѭӟFFӫDFiFKҥWVDXNӃWWLQKFyWKӇӣGҥQJPLFURKRһFQDQRQrQNKLWLӃSWөFÿѭDYjRÿӗQJKyDWKuGӉGjQJWҥRUDFiFKҥWFyNtFKWKѭӟFGҥQJQDQRYjÿӗQJQKҩW

1.2.4.3 .ӃWKӧSÿӗQJWKӡLERWWRP-up và Top-down

.ӃWKӧSQKӳQJѭXÿLӇPFӫDFiFSKѭѫQJSKiSPӝWSKѭѫQJSKiS PӟLNӃWKӧSÿӗQJ WKӡL KDL SKѭѫQJ SKiS Wop-down và bottom-up ÿѭӧF iS GөQJ 9t Gө, nghiên FӭXNANOEDGE FӫDF{QJW\Baxter EDR JӗPKDLEѭӟFULrQJELӋW 4Xi WUuQK NӃWWӫDÿѭӧFWLӃQKjQKYjNtFKWKѭӟFFӫDWKXӕFVӁJLҧPÿiQJNӇQKӡÿӗQJKyDiSVXҩWcao

Hình 1 11: Piston-gap method (A) and jet-stream method (B) [19]

1.2.5 +X\ӅQSKQDQR

&yUҩWQKLӅXWKӇFҩXWҥRFӫDFiFKҥWQDQRWURQJWKXӕFQKѭQDQRWLQKWKӇKӋQKNJQDQRQDQRFDSVXOHQDQRVSKHUHYjOLSRVRPH0ӛLORҥLWKuÿһFWUѭQJFKRQKӳQJSKѭѫQJSKiSNKiFQKDXÿӇWҥRUDVҧQSKҭP[15]

1.2.5.1 +ӋQDQRWLQKWKӇ

1KӳQJKҥWWLQKWKӇQDQRÿLӇQKuQKÿѭӧFÿLӅXFKӃEҵQJFiFKÿLӅXNKLӇQVӵNӃWWLQKYjTXiWUuQKJLҧP EӟWNtFKFӥKҥWQăQJOѭӧQJFDRcó kích WKѭӟF”QP

Quy WUuQKVҧQ[XҩWQDQRWLQKWKӇ EDRJӗPQJKLӅQѭӟWÿӗQJKRiiSVXҩWFDRKD\NӃWKӧSJLӳDTXiWUuQKNӃWWLQKYjVӵFKLDQKӓSKkQWӱEҵQJFiFKÿӗQJNӃWWӫa và ÿӗQJKRi4X\ WUuQKQj\FyEѭӟF

- &KXҭQEӏYjSKDORmQJQJX\rQOLӋX - ӃWWLQKÿӇWҥRUDKӛQKӧSFyQKӳQJKҥWFKҩWUҳQQKӓOLWLQKӳQJKҥWQj\NK{QJӗQÿӏQKYjGӉSKkQKXӹ

- ĈӗQJKRiiSVXҩWFDRQKӳQJKҥWQj\VӁEӏSKiYӥYjәQÿӏQK 1JRjLFiF\ӃXWӕNӻWKXұWWiFÿӝQJÿӃQNtFKWKѭӟFFӫDKҥWQDQRWLQKWKӇQKѭiS VXҩW QKLӋW ÿӝ Vӕ FKX NǤ ÿӗQJ KyD WUҥQJ WKiL WLQK WKӇ Yj ÿӝ FӭQJ QJX\rQOLӋX«KӋQDQRWLQKWKӇSKҧLFyÿӝәQÿӏQKFDREҵQJFiFKWKrPYjRKӋFiFFKҩWKRҥWÿӝQJEӅPһWFKҩWWăQJÿӝQKӟWFKҩWәQÿӏQKFKҩWFKӕQJWҥRPҫPWLQKWKӇ«

- &iF FKҩW KRҥW ÿӝQJ EӅ PһW WKѭӡQJ Vӱ GөQJ QKѭ ODXryl glucoside, decyl glucoside, sodium cocoamphoacetate, polyglyceryl-3 methylglucose distearate, cetearyl glucoside, Inulin lauryl carbamate, lecithin and deravatives, phospholipid, polyethylene glycol, polypropylene glycol, polysorbate (Tween20, 80)

- &KҩW WăQJ ÿӝ QKӟW FDUER[\PHWK\OFHOOXORVH VLOLFLXP GLR[LGH [DQWKDQJXP HWK\OFHOOXORVH SRO\FU\ODWHV FDUERSRO DOXPLQLXP PRQRVWHDUDWH OLSLG UҳQcarnauba wax, beeswax

- &KҩWOjPEӅQQKѭ39$39S\UROLGRQHSROR[DPHUSRO\PHÿӗQJSRO\PHFӫDSRO\R[\HWK\OHQe và polyoxypropylene oxide

- &KҩW FKӕQJ NӃW WLQK VRGLXP FLWUDWH VRGLXP K\GURJHQ SKRVSKDWHdiphosphate, sodium pyrophosphate

- &iF FKҩW FKӕQJ SKiW WULӇQ WLQK WKӇ 393 FHOOXORVH GHULYDWLYHV +30&(hydroxyl propyl methyl cellulose), HPMCAS (hydroxyl propyl methyl cellulose acetate succinate) [17]

Hình 1 13: +uQKG̩QJYjWtQKFK̭WFͯDQDQRVSKHUH

Hình 1 14: Quá trình k͇t tinh nanosphere

x ĈLӅXFKӃQDQRVSKHUH 1DQRVSKHUHFyWKӇÿѭӧFÿLӅXFKӃEҵQJKDLSKѭѫQJSKiSWUrQW\WKXӝFYjRWӯQJORҥLSRO\PHUVӱGөQJ3KѭѫQJSKiSSKәELӃQOjWKD\WKӃGXQJP{LYjNӃWWLQKGҥQJQDQRKzDWDQSRO\PHUSRO\DON\OF\DQRDFU\ODWH3$&$WURQJGXQJP{LKӳXFѫGXQJP{LWDQWURQJQѭӟFVDXÿyFKRYjRGXQJGӏFKQѭӟFFyFKӭDFKҩWKRҥWÿӝQJEӅPһW.KLÿyGXQJ P{LKӳXFѫVӁ NKXӃFK WiQTXDSKDQѭӟFSRO\PHUVӁEӏ NӃW

WLQKYjWKXӕFÿѭӧFEDREӑFWURQJQDQRVSKHUH[17]

b Nanocapsule

1DQRFDSVXOHOjGҥQJWURQJÿyWKXӕFWӗQWҥLWURQJO}LFӫDFiFSKҫQWӱQKѭOjGXQJ GӏFK UҳQ KRj WDQ KRһF KRj WDQ WURQJ GҫX Yj SRO\PHUVRPHU SRO\PHUQDQRFDSVXOHVYjSRO\PHUVRPHÿӅXOjGҥQJNHRKӋWKӕQJEӑQJYӟLWKXӕFEӏEDREӑFErQ WURQJ &iF SRO\PHU WKѭӡQJ Vӱ GөQJ QKѭ 3/$ 3/*$ Yj 3&/ KD\ FiFFRSRO\PHUFӫD3(*Yj3/$

Hình 1 15: +uQKG̩QJ và tính ch̭t cͯa nanocapsule.