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Synthesis and characterization of poly(N-isopropylacrylamide-co-L-lactide) for biodegradable stimuli-responsive drug delivery system.
 Yoon Jung Cho, Su Jin Jung, Ja Won Kim, So Ryong Lim and Hong Sung Kim
Dept. of Biomaterials Science, Pusan National University
ABSTRACT
RESULTS AND DISCUSSION
A biodegradable temperature-sensitive copolymers, Poly(N-isopropyl acrylamide -co-L-lactide), were prepared by simultaneous polymerization of N-isopropylacrylamide with L-lactide. The structure of copolymers was inspected by FT-IR spectroscopy, 1H-NMR and 13C-NMR. Sol-gel transitions of the copolymers were investigated in the aqueous solution of pH 7.0 and pH 1.2. Their solution showed reversible changes in optical properties: clear below a lower critical solution temperature(LCST) and opaque above the LCST. The properties of the copolymers were characterized by XRD, DSC and contact angle measurement.
Structure analysis of the copolymers
1H-NMR spectroscopy
FT-IR spectroscopy
INTRODUCTION
Biodegradable thermo-sensitive polymer
Thermo-sensitive polymer has been on the focus of many studies because of their ability to change according to environmental stimuli.
Aqueous solutions of thermo-sensitive polymer exhibits a lower critical solution temperature(LCST) which alter the molecular interactions between polymer chains or between a polymer chain and solutes.
This thermally reversible phase transition is a consequence of the macromolecular transition from a hydrophilic to a hydrophobic structure in aqueous solutions.
Biodegradable property required for drug delivery system.
Figure 2. 1H-NMR-spectrum of poly(N-isopropylacrylamide -co-L-lactide); mole rate of NIPAAm/L-lactide =50/50
Figure 1. FT-IR spectra of poly(N-isopropylacrylamide-co-L-lactide); C0 L-lactide ratio 0%, C1 30%, C2 50% and C3 70%
▶ In this study
- Biodegradable temperature responsive materials have been prepared by simultaneously copolymerizing the two monomer.
The structure and property of the copolymer were confirmed and it was determined the dependence of the sol-gel transition and LCST
Methylene oxide in main chain which was formed by bonding methylene of N-isopropyl crylamide to oxide of L-lactide at δ=3.3(h).
The copolymer is compo sed with the N-isoproylacryl amide/L-lactide alternative chain segment and PNIPAAm chain segment.
N-isopropylacrylamide segment : amideⅠ(C=O) 1649cm-1, amideⅡ (N-H) 1541cm-1, methyl group in -CH(CH3)2 1386cm-1
L-Lactide segment : carboxyl in L-lactide C=O 1764cm-1
EXPERIMENTAL
Copoolymerization
▶Almost carbon belong to two component peak from methine carbon(C-H)
▶ Carbon proton of the methylene CH3 δ=23ppm, C-O groups δ=72ppm, C=O groups δ=167ppm
Monomer : N-isopropylacrylamide, L-lactide
Initiator : Benzoyl peroxide
Solvent : Toluene
Polymerization time : 4 hour
Reprecipitation : Ethanol, Diethyl ether
Figure 3. 13C-NMR-spectrum of poly(N-isopropylacrylamide -co-L-lactide); mole rate of NIPAAm/L-lactide=30/70
Thermal analysis
Crystalline analysis
Surface energy
Code
Copolymers (mole %)
NIPAAm
L-lactide C0
100 C1 70 30 C2 50 C3
Surface energy
(mN/m) C0
77.15 C1
80.36 C2
83.36 C3
87.78
materials
Poly(N-isopropylacrylamide-co-L-lactide)
Table 1 Contact angle and surface energy of poly(N-isopropylacrylmaide-co-L-lactide)
Figure 5. XRD patterns of poly(N-isopropylacryl amide-co-L-lactide); (a) NIPAAm/L-lactide=100:0 (b) NIPAAm/L-lactide=50:50
Figure 4. DSC thermogram of poly(N-isopropylacryl maide-co-L-lactide)
▶ The intermolecular interaction of PNIPAAm chains were interfered by L-lactide. The amorphous phase of the copolymers is seemed to be loosen.
N-isopropylacrylamide segment
▶ The intermolecular bonding of the copolymer is considered to be getting weaker with increasing of L-lactide proportion.
▶ The microstructure of the copolymer were considered to exist only the crystalline phase of PNIPAAm.
represents to have a thermally reversible property
exhibits a lower critical solution temperature(LCST) :32℃
L-lactide segment
Sol-gel transition
has the hydrophobic segment for micelle-forming
well known as a biodegradable polymer
Instrumental analysis
Fourier Transformation infrared spectroscopy (FT-IR)
- IRAffinity-1, Shimadzu corp, Japan.
- wavelength range of to by the KBr pellet technique.
Nuclear Magnetic resonance spectroscopy (NMR)
- 1H-NMR & 13C-NMR
- Joel JNM-al 400 FT-system spectrometer at 300MHz
29℃
31℃
Figure 7. Photographs of poly(N-isopropylacrylamide-co-L-lactide) near LCST; C0, C1, C2 and C3 from left side in each images
▶ As the hydrophobic ratio was increased by L-lactide, temperature of reversible phase transition was changed.
Figure 6. Sol-gel transition of poly(N-isopropylacrylamide-co-L-lactide) (a) in pH 7.0 and (b) in pH 1.2
Differential scanning calorimetry (DSC)
- Q20 V24.2 build 116 at a scanning rate of 5℃/min
X-ray diffraction analysis
- DMAX 2000V vertical diffractometer, Rigaku corp, Japan
- monochromatic Cuka radiation at 40kV, 30mA, and a scan speed 10°/min
[1] Chang Kwon Han and You Han Bae, Inverse thermally-reversible gelation of aqueous N-isopropylacrylamide copolymer solutions, Polymer, 1997; 97:
[2] M.S. Jones, Effect of pH on the lower critical solution temperatures of random copolymers of N-isopropylcrylamide and acrylic acid, european polymer journal, 1999;35:
[3] Young-Sung Kim, Min-Ae Bae, and Koo-Sik Yoon+, Synthesis and characterization of poly(N-isopropylacrylamide) containing polydimethylsiloxane. Korean Chemical Society. 2001;45:
[4] You YZ, Hong CY, Wang WP, Lu WQ and Pan CY, Preparation and characterization of thermally responsive and biodegradable block copolymer comprised of PNIPAAM and PLA by combination of ROP and RAFT methods, Macromolecules, 2004; 37:
[5] Minoo-Rabeeh-Hobabi, Davooud Hassanzadeh, Shirzad Azarmi and A.A. Entezami., Effect of synthesis method and buffer composition on the LCST of a smart copolymer of N-isopropylacrylamide and acrylic acid, POLYMERS FOR ADVANCED TECHNOLOGIES. 2007;18:
For biodegradable stimuli-responsive polymer, poly(N-isopropylacrylamide-co-L-lactide) was prepared by simultaneous polymerization.
The structure of copolymers is composed with the NIPAAm/L -lactide alternative chain segment and PNIPAAm chain segment.
The microstructure of the copolymers was only the crystalline phase of PNIPAAm
With increasing of L-lactide proportion, the intermolecular bonding of the copolymer chains is getting weaker and the surface energy of the copolymers increased
The reversible sol-gel transition of the copolymer was occurred on the range of 29~37℃. Depending on the ratio of L-lactide, transition temperature can be controlled.
CONCLUSION
REFERENCES
Contact angle meter
- AMS2001C-1, Mirero system, Korea
- Surface energy measurement using Ethylene Glycol.
Sol-gel transition
- Temperature increasing was carried out at 1℃ intervals from 25 to 40℃.
- The gelation temperature was determined in cloud, solid, dissolution point.
Department of Biomaterial Sciences ( kr) ac.