Studies on thermoresponsive polymers:Phase behaviour,drug delivery and biomedical applications

The present review aims to highlight the applications of thermoresponsive polymers.Thermo-responsive polymers show a sharp change in properties upon a small or modest change in temperature.This behaviour can be utilized for the preparation of so-called‘smart’drug delivery systems,which mimic biological response behaviour to a certain extent.Such materials are used in the development of several applications,such as drug delivery systems,tissue engineering scaffolds and gene delivery.Advances in this field are particularly relevant to applications in the areas of regenerative medicine and drug delivery.This review addresses summary of the main applications of thermoresponsive polymers which are categorized based on their 3-dimensional structure;hydrogels,interpenetrating networks,micelles,films and particles.The physico-chemical behaviour underlying the phase transition is also discussed in brief.

Spectral Insights into Microdynamics of Thermoresponsive Polymers from the Perspective of Two-dimensional Correlation Spectroscopy

Generalized two-dimensional correlation spectroscopy （2DCOS） and its derivate technique, perturbation correlation moving window （PCMW）, have found great potential in studying a series of physico-chemical phenomena in stimuli-responsive polymeric systems. By spreading peaks along a second dimension, 2DCOS can significantly enhance spectral resolution and discern the sequence of group dynamics applicable to various external perturbation-induced spectroscopic changes, especially in infrared （IR）, near-infrared （NIR） and Raman spectroscopy. On the basis of 2DCOS synchronous power spectra changing, PCMW proves to be a powerful tool to monitor complicated spectral variations and to find transition points and ranges. This article reviews the recent work of our research group in the application of 2DCOS and PCMW in thermoresponsive polymers, mainly focused on liquid crystalline polymers and lower critical solution temperature （LCST）-type polymers. Details of group motions and chain conformational changes upon temperature perturbation can thus be elucidated at the molecular level, which contribute to the understanding of their phase transition nature.

Thermoresponsive dendronized copolymers for protein recognitions based on biotin-avidin interaction

Thermoresponsive biotinylated dendronized copolymers carrying dendritic oligoethylene glycol（OEG）pendants were prepared via free radical polymerization,and their protein recognitions based on biotin-avidin interaction investigated.Both first（PG1） and second generation（PG2） dendronized copolymers were designed to examine possible thickness effects on the interaction between biotin and avidin.Inherited from the outstanding thermoresponsive properties from OEG dendrons,these biotinylated cylindrical copolymers show characteristic thermoresponsive behavior which provides an envelope to capture avidin through switching temperatures above or below their phase transition temperatures（T_（cp）s）.Thus,the recognition of polymer-supported biotin with avidin was investigated with UV/vis spectroscopy and dynamic laser light scattering.In contrast to the case for PG1,the increased thickness for copolymer PG2 hinders partially and inhibits the recognition of biotin moieties with avidin either below or above its T_（cp）.This demonstrates the significant architecture effects from dendronized polymers on the biotin moieties to shift onto periphery of the collapsed aggregates,which should be a prerequisite for protein recognition.These kinds of novel thermoresponsive copolymers may pave a way for the interesting biological applications in areas such as reversible activity control of enzyme or proteins,and for controlled delivery of drugs or genes.

Preparation and Characterization of Thermoresponsive Hyperbranched Polyethylenimine with Plenty of Reactive Primary Amine Groups

Certain amount of primary amine （NH2） groups of hyperbranched polyethylenimine （HPEI） was first protected by Boc groups. Subsequently, the residual reactive amine groups were reacted with isobutyric anhydride to introduce isobutyramide （IBAm） groups to HPEI. Finally, Boc groups were deprotected to result in HPEI-IBAm-NH2 with 18% of primary amine terminals on the periphery and 80% of IBAm terminal groups （abbreviated as HPEI-IBAm0.80-NH2）. 1H-NMR characterization proved the successful preparation of the product in each step. Compared with its spatial isomer HPEI- IBAm0.8o without primary amine groups, IH-NMR spectra verified that more IBAm groups were located in the interior of HPEI-IBAm0.80-NH2. The further modification of HPEI-IBAmo.so-NH2 and HPEI-IBAmo.8o with p-nitrobenzaldehyde demonstrated that HPEI-IBAm0.so-NH2 was more reactive than HPEI-IBAm0.80 due to its possession of primary amines. Turbidimetry measurements showed that HPEI-IBAm0.80-NH2 was thermoresponsive in water. In the pH range of 9.5-10 its cloud point temperature （Top） was constant, and it increased obviously upon decreasing the pH below 9.5. The thermoresponsive HPEI-IBAmo.8 exhibited the similar trend, but the pH threshold to achieve the constant Top was around 8.5. Moreover, HPEI-IBAm0.8-NH2 showed higher Top and broader phase transition than HPEI-IBAm0.8. The mechanism leading to the different thermoresponsive properties between HPEI-IBAm0.8-NH2 and its spatial isomer HPEI-IBAm0.8 was discussed.

Construction of Self-Reporting Biodegradable CO_(2)-Based Polycarbonates for the Visualization of Thermoresponsive Behavior with Aggregation-Induced Emission Technology

Thermoresponsive polymers with simultaneous biodegradability and signal“self-reporting”outputs that meet for advanced applications are hard to obtain.To address this issue,we developed fluorescence signal“self-reporting”biodegradable thermoresponsive polycarbonates through the immortal copolymerization of CO_(2)and oligoethylene glycol monomethyl ether-functionalized epoxides in the presence of hydroxyl-modified tetraphenylethylene(TPE-OH).TPE-OH was used as chain transfer agent to afford well-defined polycarbonates with controlled molecular weight(6000—17000 g·mol^(–1))and aggregation-induced emission characteristics.Through temperature-dependent fluorescence intensity study,low critical solution transition of TPE-labeled polycarbonates were determined and the fine details of thermal-induced phase transition process were monitored.Further research indicated that temperature-controlled aggregation and dissociation of TPE moieties are the main reason for fluorescence intensity variations.We anticipate that this work could offer a method to visualize the thermal transition process of thermoresponsive polycarbonates and broaden their application fields as smart materials.

Influence of Aliphatic Amide Terminals on the Thermoresponsive Properties of Hyperbranched Polyethylenimines

Acetamide （C2）, propionamide （C3）, butyramide （C4）, isobutyramide （i-C4）, isovaleramide （i-C5） and trimethylacetamide （t-C5） groups each were introduced to the terminals of hyperbranched polyethylenimine （HPEI） through the amidation reaction between HPEI and the corresponding anhydride. Moreover, HPEIs terminated with two kinds of amides were also prepared. The first amide was fixed to be i-C4 with 52% degree of amidation （DA）, and the second amide varied from C2, C3, C4, i-C5 to t-C5. All the polymers were characterized by 1H-NMR. Turbidimetry measurements were performed for these polymers in water at different temperatures. With respect to the polymers bearing only one kind of amide group, except C2, all the other amide groups could render thermoresponsive properties to HPEI. The specific ordering of these amide groups to reduce the cloud point temperature （Top） was as follows： i-C5 〉 t-C5 〉 C4 〉 i-C4 〉 C3. Moreover, the more branched i-C4 and t-C5 were better groups than their less branched isomers C4 and i-C5 in the Tcp range of 12-51 ~C to render the sharper phase transition to the thermoresponsive polymers. As for the polymers bearing two kinds of amide groups, the further introduction of C2, C3, C4, i-C5 or t-C5 could effectively endow HPEI bearing 52% of i-C4 with thermoresponsive properties. The specific ordering of these second amide groups to reduce the Top was as follows： i-C5 〉 C4 〉 i-C4 〉 C3 〉 C2. C4, i-C5 and t-C5 were all effective second amide groups to prepare the thermoresponsive polymers with sharper phase transition.