Tun-Fun Way

Preparation of thermo- and pH-responsive star copolymers via ATRP and its use in drug release application

A star-shaped copolymer, poly(N-isopropylacrylamide-co-itaconamic acid (poly(NIPAAm-co-IAM)), being pH- and thermo-dual-responsive, was synthesized by atomic transfer radical polymerization (ATRP) and characterized in this work. The lower critical solution temperature (LCST) of the star copolymer increases with the molar fraction of IAM. The particle size decreases as the temperature increases but increases as the pH value increases. Transmission electron microscopy (TEM) reveals that the star-shaped copolymer has a near-spherical core-shell structure that favors drug delivery. The star copolymer can be used in drug encapsulation as well as drug release. The star copolymer has different drug release rates in environments of different pH, and thus it can carry drugs in an acidic (gastric) environment and release the drugs in a neutral or less acidic (intestinal) environment.

Synthesis and characterization of hyperbranched copolymers hyper-g-(NIPAAm-co-IAM) via ATRP

A hyperbranched copolymer, hyperbranched-g-(N-isopropylacrylamide-co-itaconamic acid) (“hyperbranch-g-(NIPAAm-co-IAM)”), serving as a pH- and thermo-responsive material, was synthesized via atomic transfer radical polymerization (ATRP) and characterized in this study. A macroinitiator was prepared from a commercially available hyperbranched polymer, “hyperbranched bis-(methylol)propionic acid (bis-MPA) polyester-16-hydroxyl, generation 2” (hyperbranch-OH) and used as a core structure of the hyperbranched copolymer. The hyperbranch-OH has 16 hydroxyl groups; among them, 12 arms were derived from substitution of the hydroxyl groups with poly(NIPAAm-co-IAM) by ATRP. The polydispersity index (PDI) of the newly synthesized hyperbranched copolymer can be controlled to be less than 1.4. The hyperbranched copolymer shows more significant size change as the environmental pH value changes, compared to the linear random poly(NIPAAm-co-IAM). The particle size decreases with temperature but increases with the pH value. As the molar fraction of IAM in the hyperbranched copolymer increases, the lower critical solution temperature (LCST) increases. Hyperbranch-g-(NIPAAm-co-IAM) with a molar ratio of NIPAAm/IAM equaling to 3:1 shows a LCST of the aqueous solution close to the body temperature, indicating potential use in biomedical applications such as drug release.

A study of thermal stability of polyester containing phenyl phosphonate unit for flame retardant fiber

Abstract Phenyl phosphonic acid (PPA) was chosen as a comonomer to manufacture flame retardant polyester fiber. The yield based on PPA is less than 55% by a conventional polyester formation process. Different factors which might affect the yield of the copolymerization were investigated. The phosphorus residues in the reactor during the process of polymerization were monitored. It is found that the phosphorus residues decrease sharply in the high vacuum stage. This indicates that factors which increase the molecular weight of the prepolymer containing phenyl phosphonate unit will promote the yield of the copolymerization. In order to get an insight into the low yield of the copolymerization, the compounds containing phenyl phosphonate unit, bis(2-naphtholyloxyethyl) phosphonate (BNEP) and bis( p -methoxycarbonyl phenyl) phosphonate (BMPP) were synthesized for model studies. The preliminary results showed that these compounds decompose significantly above 240 °C. This suggests that the low yield of the PPA polymerization process may be attributed to the thermal instability of the OP bond in the phenyl phosphonate unit at the polymerization temperature.

Synthesis and Drug Delivery Application of Thermo- and pH-Sensitive Hydrogels: Poly(β-CD-co-N-Isopropylacrylamide-co-IAM)

Copolymerization of N-isopropylacrylamide (NIPAM), itaconamic acid (IAM; 4-amino-2-methylene-4-oxobutanoic acid) and β-cyclodextrin was investigated in this study. β-cyclodextrin was at first modified by reacting with allyl glycidyl ether to substitute its OH end groups with moieties containing double bonds to facilitate the subsequent radical copolymerization with NIPAM and IAM. It was reported that poly(NIPAM-IAM) can respond to the change of temperature as well as pH value. In this study, the structure of β-cyclodextrin was introduced to poly(NIPAM-IAM) copolymers because of its cavity structure capable of encapsulating a variety of drug molecules. The tri-component copolymers, poly(CD-NIPAM-IAM), were synthesized with different monomeric ratios of NIPAM/IAM/β-CD and the hydrogels of the tri-component copolymers were also synthesized by additionally adding N,N′-methylenebisacrylamide as a cross-linking agent. The results show that the lower critical solution temperature (LCST) of the copolymer (or hydrogel) increases as the molar fraction of IAM increases. The transmission electron microscopic (TEM) images of linear copolymers (no cross-linking) show that molecules undergo self-assembly to have a distinct core–shell structure, compared to poly(CD-NIPAM) which contains no IAM. On the other hand, the scanning electron microscopic (SEM) images of hydrogels show that the pores gradually become sheet-like structures as the molar fraction of IAM increases to enhance the water absorption capacity. In order to exhibit the thermal and pH sensitivities of poly(CD-NIPAM-IAM) as the drug carrier, the drug release of the newly synthesized hydrogels at 37 °C and different pH values, pH = 2 and pH = 7.4, was investigated using atorvastatin which was used primarily as a lipid-lowering drug. The drug release experimental result shows that poly(CD-NIPAM-IAM) as a drug carrier was pH-sensitive and has the largest release rate at pH = 7.4 at 37 °C, indicating it is useful to release drugs in a neutral or alkaline (intestinal) environment.

Synthesis and Characterization of pH and Thermo Dual-Responsive Hydrogels with a Semi-IPN Structure Based on N-Isopropylacrylamide and Itaconamic Acid

A series of semi-interpenetrating polymer network (semi-IPN) hydrogels were synthesized and investigated in this study. Linear copolymer poly(N-isopropylacrylamide-co-itaconamic acid) p(NIPAM-co-IAM), which is formed by copolymerization of N-isopropylacrylamide (NIPAM) and itaconamic acid (IAM, 4-amino-2-ethylene-4-oxobutanoic acid), was introduced into a solution of NIPAM to form a series of pH and thermo dual-responsive p(NIPAM-co-IAM)/pNIPAM semi-IPN hydrogels by free radical polymerization. The structural, morphological, chemical, and physical properties of the linear copolymer and semi-IPN hydrogels were investigated. The semi-IPN hydrogel showed high thermal stability according to thermal gravimetric analyzer (TGA). Scanning electronic microscopy (SEM) images showed that the pore size was in the range of 119~297 µm and could be controlled by the addition ratio of the linear copolymer in the semi-IPN structure. The addition of linear copolymer increased the fracture strain from 57.5 ± 2.9% to 91.1 ± 4.9% depending on the added amount, while the compressive modulus decreased as the addition increased. Moreover, the pH and thermo dual-responsive properties were investigated using differential scanning calorimetry (DSC) and monitoring the swelling behavior of the hydrogels. In deionized (DI) water, the equilibrium swelling ratio of the hydrogels decreased as the temperature increased from 20 °C to 50 °C, while it varied in various pH buffer solutions. In addition, the swelling and deswelling rates of the hydrogels also significantly increased. The results indicate that the novel pH-thermo dual-responsive semi-IPN hydrogels were synthesized successfully and may be a potential material for biomedical, drug delivery, or absorption application.

Thermal analysis and melt spinnability of poly(acrylonitrile-co-methyl acrylate) and poly(acrylonitrile-co-dimethyl itaconate) copolymers

This work investigated the cyclization possibility and melt spinnability of carbon fiber precursors, poly(acrylonitrile-co-methyl acrylate) (AN/MA) and poly(acrylonitrile-co-dimethyl itaconate) (AN/DMI). The onset temperature of cyclization of the AN/DMI copolymer is lower than that of the AN/MA copolymer and also the polyacrylonitrile (PAN) homopolymer. The enthalpy (ΔH) of the AN/DMI copolymer is about 3–4 times that of the PAN homopolymer and about 1.8 times that of the AN/MA copolymer, indicating that the degree of cyclization of the AN/DMI copolymer is relatively higher. The melt dwell time of the AN/DMI copolymer is increased to about 3–5 times that of the AN/MA copolymer, especially when synthesized with a feed molar ratio of AN/DMI = 85/15. The AN/DMI copolymer (AN/DMI = 85/15) has the longest melt dwell time, 24.8 min, at the lowest melting temperature, 190oC, among all the PAN-related copolymers synthesized herein. Furthermore, the AN/DMI copolymer (AN/DMI = 85/15) can be rapidly cyclized at the cyclization temperature of 260℃, which is 25℃ lower than that of the AN/MA copolymer (AN/MA = 85/15). In short, this work demonstrates that the carbon fiber precursor made by the AN/DMI copolymer (AN/DMI = 85/15) will be superior to that of the AN/MA copolymer (AN/MA = 85/15) with respect to the melt spinnability and cyclization at low temperature.

Study of theThermo-/pH-Sensitivity of Stereo-Controlled Poly(N-isopropylacrylamide-co-IAM) Copolymers via RAFT Polymerization

In this work, a smart copolymer, Poly(nipam-co-IAM) was synthesized by copolymerization of N-isopropylacrylamide (nipam) and itaconamic acid (IAM) through reversible addition-fragmentation chain-transfer (RAFT) polymerization. Poly(nipam-co-IAM) has been studied previously synthesized via radical polymerization without stereo-control, and this work used cumyl dithiobenzoate and Ytterbium(III) trifluoromethanesulfonate as RAFT and stereo-control agents, respectively. The stereo-control result in this work shows that tacticity affects the lower critical solution temperature (LCST) and/or the profile of phase separation of Poly(nipam-co-IAM). In the pH 7 and pH 10 buffer solutions, the P(nipam-co-IAM) copolymer solutions showed soluble–insoluble–soluble transitions, i.e., both LCST and upper critical solution temperature (UCST) transitions, which had not been found previously, and the insoluble to soluble transition (redissolved behavior) occurred at a relatively low temperature. The insoluble to soluble transition of P(nipam-co-IAM) in alkaline solution occurred at a temperature of less than 45 °C. However, the redissolved behavior of P(nipam-co-IAM) was found only in the pH 7 and pH 10 buffer solutions and this redissolved behavior was more prominent for the atactic copolymers than in the isotactic-rich ones. In addition, the LCST results under our experimental range of meso content did not show a significant difference between the isotactic-rich and the atactic P(nipam-co-IAM). Further study on the soluble-insoluble-soluble (S-I-S) transition and the application thereof for P(nipam-co-IAM) copolymers will be conducted.