Synthesis and Characterization of Stimuli-Responsive Chitosan-Based Nanoparticles
Date Issued
2010
Date
2010
Author(s)
Chuang, Chung-Yang
Abstract
In this research, chitosan-based stimuli-responsive nanoparticles were prepared by different polymerization method. Structure, morphology, environmental sensitive behavior and application in drug release were studied in this research.
In the first part, polyelectrolyte complex particles of chitosan-poly(acrylic acid) (CS-PAA) through polymerization of acrylic acid (AA) in the presence of chitosan (CS). The prepared CS-PAA complex particles had positive zeta potential and dispersed very well in the aqueous solution. Structure and morphology of complex particles were investigated with the changes in the feeding molar ratio of glucosamine unit in CS to AA monomer. It was found at a molar ratio of 1.0/1.1, a hollow structure in complex particles was observed after polymerization. The synthesized complex particles were environmentally sensitive in which their mean diameter could change with the pH value of medium. Moreover, the complex particles showed a continuous release of the encapsulated doxycycline hyclate up to 8 days. These complex particles with environmentally sensitive properties are expected to be utilized in the hydrophilic drug delivery system.
In the second part, thermo- and pH-responsive chitosan-based nanoparticles were synthesized via the surfactant-free emulsion polymerization. The thermal/pH dual responsive properties of these nanoparticles were designed by the addition of a pH sensitive monomer, acrylic acid (AA), to be copolymerized with N-isopropylacrylamide (NIPAAm) in a chitosan (CS) solution. The molar ratio of CS/AA/NIPAAm in the feed was changed to investigate its effect on structure, morphology, thermo- and pH-responsive properties of the nanoparticles. It was found that CS-PAA-PNIPAAm nanoparticles could be well dispersed in the aqueous solution and carried positive charges on the surface. The addition of thermal-sensitive NIPAAm monomer affected the polymerization mechanism and interactions between CS and AA. The particle size of the nanoparticles was found to be varied with the composition of NIPAAm monomer in the feed. The synthesized nanoparticles exhibited stimuli-responsive properties, and their mean diameter thus could be manipulated by changing pH value and temperature of the environment. The nanoparticles showed a continuous release of the encapsulated doxycycline hyclate up to 10 days during an in-vitro release experiment. The environmentally responsive nanoparticles are expected to be utilized in many fields such as drug delivery system.
In the third part, thermo- and pH-responsive chitosan-based porous nanoparticles were prepared by the temperature-dependent self assembly method. The chitosan-graft-poly(N-isopropylacrylamide) (CS-g-PNIPAAm) copolymer solution was prepared through polymerization of N-isopropylacrylamide (NIPAAm) monomer in the presence of chitosan (CS) solution using cerium ammounium nitrate as the initiator. Then, CS-g-PNIPAAm solution was diluted by deionized water and heated to 40℃ for CS-g-PNIPAAm self-assembly. After that, CS-g-PNIPAAm assembled to form micelles in which shell layer was CS. Crosslinking agent was used to reinforce the micelle structure to form nanoparticle. The molar ratio of CS/NIPAAm in the feed mixture was changed to investigate its effect on structure, morphology, thermo- and pH-responsive properties of the nanoparticles. TEM images showed that a porous structure of nanoparticles was developed. The synthesized nanoparticles carried positive charges on the surface and exhibited stimuli-responsive properties, and their mean diameter thus could be manipulated by changing pH value and temperature of the environment. The nanoparticles showed a continuous release of the encapsulated doxycycline hyclate up to 10 days during an in-vitro release experiment. These porous particles with environmentally sensitive properties are expected to be utilized in hydrophilic drug delivery system.
In the fourth part, stimuli-responsive porous/hollow nanoparticles were prepared by the self assembly of CS-based graft copolymers. The chitosan-graft-poly(N-isopropylacrylamide) (CS-g-PNIPAAm) copolymer solution was prepared through polymerization of N-isopropylacrylamide (NIPAAm) monomer in the presence of chitosan (CS) solution using cerium ammounium nitrate as the initiator. Then, CS-g-PNIPAAm copolymers were dissolved in acetic acid aqueous solution and heated to 40℃ for CS-g-PNIPAAm self-assembly. After that, CS-g-PNIPAAm assembled to form micelles and crosslinking agent was used to reinforce the micelle structure to form nanoparticles. The molecular weight of grafted PNIPAAm on CS chains was changed to investigate its effect on structure, morphology, thermal- and pH-responsive properties of the nanoparticles. TEM images showed that a porous or hollow structure in the interior of nanoparticles was developed. The synthesized nanoparticles carried positive charges on the surface and exhibited stimuli-responsive properties, and their mean diameter thus could be manipulated by changing pH value and temperature of the environment. The nanoparticles showed a continuous release of the encapsulated doxycycline hyclate up to 10 days during an in-vitro release experiment. These porous/hollow particles with environmentally sensitive properties are expected to be utilized in drug release.
In the fifth part, the model of drug release behavior of CS-based nanoparticles was developed from Fick’s second law. According to the structure and the release environment of nanoparticles, the theoretical relationship between drug release amount and release time for different structure CS-based nanoparticles was developed. Compared with experiment results, the range of diffusivity for encapsulated-drug in the nanoparticles was evaluated.
Subjects
chitosan
acrylic acid
N-isopropylacrylamide
stimuli-responsive
controlled release
nanoparticles
self-assembly
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-99-D95549003-1.pdf
Size
23.53 KB
Format
Adobe PDF
Checksum
(MD5):ae1fb5d99858354ad875890e98952a63