Temperature/pH-induced morphological regulations of shell cross-linked graft copolymer assemblies

Shell cross-linked (SCL) assemblies are prepared from the thermally induced three-layered, onion-like micelles of graft copolymers comprising acrylic acid (AAc) and 2-methacryloylethyl acrylate (MEA) as the backbone units and poly(N-isopropylacrylamide) (PNIPAAm) and monomethoxy poly(ethylene glycol) (mPEG) as the grafts via radical polymerization of the MEA residues within the AAc-rich interfacial layers in the aqueous phase of pH 5.0 at 60 °C. The resulting nanosized SCL assemblies exhibit versatile structural regulations in a fully reversible manner in response to changes in pH and temperature. At 20 °C, SCL assemblies retain the morphology of vesicle-like hollow microspheres with pH-controlled water influx and particle size. At pH 7.0, SCL assemblies remain invariant in both vesicular structure and size irrespective of the temperature increase beyond the coil-to-globule phase transition of PNIPAAm grafts occurring primarily in a highly individual manner. When the temperature increases from 20 to 60 °C at pH 5.0, the hollow particle size is greatly reduced, accompanied by the development of hydrophobic, impermeable PNIPAAm lumens attached to the inside surfaces of the interfacial gel layers. In addition, SCL assemblies undergo a dramatic thermally induced transformation from the vesicle-like to micelle-like morphology by virtue of yielding hydrophobic PNIPAAm inner cores at pH 3.0. The thermally evolved morphology of SCL assemblies is governed by the vesicle structure in response to the effect of pH on the AAc ionization within the interfacial gel layers at ambient temperature.     

Poly(ethoxytriethyleneglycol acrylate) cryogels as novel sustained drug release systems for oral application

Novel temperature sensitive cryogels of poly(ethoxytriethyleneglycol acrylate) (PETEGA), with in situ entrapped active substance, are synthesized employing the UV irradiation technique and tested as matrix for controlled release of the hydrophilic drug verapamil hydrochloride. PETEGA cryogels are non-toxic materials and, due to the macroporous structure, exhibit a reversible, ultra-rapid volume phase transition at temperature ca. 31 °C. Carriers based on PETEGA cryogels possess sustained release of verapamil hydrochloride over a period of more than 8 h, which is attributed to the hydrophobic state of the polymer network at physiological temperature and the method of drug immobilization. Drug release characteristics of PETEGA cryogels are compared with another cryogel systems, based on polyacrylamide (PAAm), poly(N-isopropylacrylamide) (PNIPAAm) and poly(2-hydroxyethyl methacrylate) (PHEMA), obtained via the same method.     

Toward an understanding of thermoresponsive transition behavior of hydrophobically modified N-isopropylacrylamide copolymer solution

Poly(N-isopropylacrylamide-co-vinyl laurate)(PNIPAAm-co-VL) copolymers were prepared at various feed ratios via conventional radical random copolymerization. The formation, composition ratios and molecular weight of copolymers were examined. The thermoresponsive behaviors of PNIPAAm and PNIPAAm-co-VL solutions at low and high concentrations were intensively investigated by turbidity measurement, Micro-DSC, temperature-variable state fluorescence, ¹H NMR and dynamic light scattering (DLS). Several important results were obtained that (1) incorporation of PVL results in much lower and broader LCST regions of the copolymer solutions, and facilitates the formation of hydrophobic microdomains far below LCST, causing a pronounced aggregation in solutions (2) temperature-variable ¹H NMR spectra shows that during the phase transition, the ‘penetration’ of PNIPAAm into the hydrophobic core is a process accompanied with a transition of isopropyl from hydration to dehydration as well as a self-aggregation of hydrophobic chains at different temperature stages (3) according to the ¹H NMR spectra of polymer solutions obtained at varied temperatures, the microdomains from hydrophobic VL moieties have a different accessibility for isopropyl groups and the entire chains during phase transition (4) temperature-variable DLS demonstrates that the temperature-induced transition behavior of copolymers is supposedly divided into three stages: pre-LCST aggregation (<20 °C), coil-globule transition at LCST (20-25 °C) and post-LCST aggregation (>25 °C).     

Mixed micelles from methoxy poly(ethylene glycol)–polylactide and methoxy poly(ethylene glycol)–poly(sebacic anhydride) copolymers as drug carriers

mPEG–PLLA (poly l-lactic acid) is synthesized by ring-opening polymerization of lactide and conjugation with mPEG. Sebacic acid is modified with acetic anhydride and condensed with mPEG to form mPEG–PSA (poly sebacic anhydride). The micelles formed by mPEG–PLLA are characterized by slow degradation and low drug encapsulation efficiency; on the contrary, mPEG–PSA micelles are characterized by rapid degradation but high encapsulation efficiency. They can merge into spherical micelles (Φ = 140 nm) by self-assembly in water. The mixed micelles can successfully encapsulate a typical hydrophobic drug (curcumin), and significantly improve its solubility. Experimental results show that the mixed micelles have the features of high encapsulation efficiency and slow degradation.     

Phase behavior of poly(N-isopropylacrylamide) in water-methanol cononsolvent mixtures and its relevance to membrane formation

The phase behavior of poly (N-isopropylacrylamide) (PNIPAAm) in solutions composed of water and methanol was studied at 25 °C. The pair of solvents used to dissolve PNIPAAm has been selected for the purpose to perform a cononsolvent system. From the observed phase behavior, PNIPAAm was soluble in either water or methanol individually but liquid-liquid demixing was observed in water/methanol mixtures. Flory-Huggins formalism including three binary interaction parameters and one ternary interaction parameter was used to analyze the phase behavior of the cononsolvent system. The mechanism of cononsolvency and its relation with the ternary interaction parameter were discussed. In addition, the use of two solvents serving as a cononsolvent system, replacing the traditional solvent-nonsolvent pair, for the membrane formation was investigated. Regardless of water or methanol being used as the solvent, it showed a rapidly precipitating system and macrovoid morphology due to liquid-liquid demixing was obtained. Trend expected on the basis of the phase diagram was in reasonable agreement with the observed membrane morphology. Therefore, the principles of membrane formation established for the ternary systems with nonsolvent-solvent-polymer can be extended to a cononsolvent-polymer system.     

Synthesis of star poly(N-isopropylacrylamide) by β-cyclodextrin core initiator via ATRP approach in water

Star poly(N-isopropylacrylamide) (PNIPAAm) based on a β-cyclodextrin (β-CD) core macroinitiator was synthesized by means of atomic transfer radical polymerization (ATRP) in water using copper(I)/2,2bipyridyl complex as a catalytic system at temperature above the lower critical solution temperature (LCST) of the PNIPAAm. The macroinitiator was prepared by the transesterification reaction of the (β-CD) with 2-bromopropionyl bromide. The LCST of the samples upshifts slightly when the absolute molecular mass of the star PNIPAAm increases. Over the phase transition, the solutions became bluish opalescent due to formation of a heterogeneous phase system consisting of collapsed polymer particles in water. Atomic force microscopy and dynamic light scattering analyses indicated two populations of self-assembled polymer structure: a larger population and a smaller population. The smaller size suggests to self-assembly of polymer micelles and the large one corresponds to aggregates of polymer micelles or star polymers coupled. Polydispersity of the star PNIPAAm ranged from 1.60 to 4.04 within 15 h of reaction, which was attributed to the collapse of the PNIPAAm chains at temperature above the LCST that causes a decrease of the polymer reactivity. This was also attributed to the star–star coupling that generates twice the value of the polydispersity for any time before 15 h of polymerization.     

Fabrication of star-shaped, thermo-sensitive poly(N-isopropylacrylamide)-cholic acid-poly(?-caprolactone) copolymers and their self-assembled micelles as drug carriers

Novel star-shaped copolymers, comprised of a thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAm) segment and three hydrophobic poly(?-caprolactone) (PCL) arms were fabricated. The copolymers were prepared by stannous octoate (Sn(Oct)₂) catalyzed ring-opening polymerization of ?-caprolactone (CL) using cholic acid functionalized PNIPAAm as the macroinitiator. The lower critical solution temperatures (LCST) of the copolymer solutions are attractively close to the nominal physiologic temperature at around 37 °C. The in vitro cytotoxicity test indicated no apparent cytotoxicity. The amphiphilic star-shaped copolymers were capable of self-assembling into spherical micelles in water at room temperature, and they possessed low critical micelle concentrations (CMCs) of 3 ∼ 8 mg/L in aqueous solution determined by fluorescence spectroscopy using pyrene as a probe. Transmission electron microscopy (TEM) measurement showed that the micelles exhibited a spherical shape with a size range of 30 ∼ 75 nm in diameter. In addition, the anticancer drug, methotrexate (MTX) can be loaded effectively in the polymeric micelles and its release was temperature-stimulated, which suggests that these materials have good potential as “intelligent” drug carriers.     

A infrared spectroscopic study on the mechanism of temperature-induced phase transition of concentrated aqueous solutions of poly(N-isopropylacrylamide) and N-isopropylpropionamide

FTIR in combination with perturbation correlation moving window (PCMW) technique was applied to study the phase transition of concentrated aqueous solutions of Poly(N-isopropylacrylamide) (PNIPAM) and its small molecular model compound N-isopropylpropionamide(NIPPA). It was found that lower critical solution temperature (LSCT) of 40% NIPPA/D₂O solution was 39 °C which was higher by ca. 8 °C than that of PNIPAM, and that NIPPA exhibited much wider temperature ranges of phase transition from 30 to 50 °C while PNIPAM underwent the phase separation in a narrow temperature range (29.1-33.1 °C). Moreover, we utilized two-dimensional correlation infrared spectroscopy (2DIR) analysis to reveal that the presence of main chains didn't affect the sensitivity and changing sequence of different groups, but did have a strong effect on the size of aggregation and formation of hydrogen bonds between carbonyl groups and water molecules. Without the interference of hydrophobic main chains, the carbonyls of NIPPA (1600 cm⁻¹) could interact with more water than those of PNIPAM (1627 cm⁻¹) below LSCT, which was the reason of the slower and milder phase transition taking place in NIPPA system.     

Thermal transitions of poly(N-isopropylmethacrylamide) in aqueous solutions

Thermal transitions of poly(N-isopropylmethacrylamide) (PIPMAm) in aqueous solutions were studied in a wide temperature range from −100 to 60 °C. The solutions of different polymer weight fractions (c=0.03-1) were investigated in cooling and heating scans of differential scanning calorimetry; four qualitatively different kinds of thermograms were identified in dependence of the fraction, c. The transitions are explained in a thermodynamic framework based on the phase diagram of the system. This diagram provides a complete understanding of thermal transitions in aqueous PIPMAm solutions as a function of c, in particular the existence of non-crystallizable water and the temperature induced phase transition that is due to the hydrophobic interaction in PIPMAm solutions.     

Influence of charge density on rheological properties and dehydration dynamics of weakly charged poly(N-isopropylacrylamide) during phase transition

It is well-known that introduction of charged groups to poly(N-isopropylacrylamide) (PNIPAM) raises its phase transition temperature. However, the influence of charged groups on structural evolution and dehydration dynamics of weakly charged PNIPAM during phase transition still lacks systematic investigation. In the current study, armed with rheometer and two-dimensional Fourier transform infrared spectrometer (2D-FTIR), we investigated on mesoscopic and microscopic scales the phase transition of sodium poly(N-isopropylacrylamide-co-2-acrylamido-2-methylpropanesulfonate), abbreviated as poly(NIPAM-co-NaAMPS), with charge density of 1–10%. At ambient temperature, scaling exponent of poly(NIPAM-co-NaAMPS) varies from that of neutral polymer to polyelectrolytes as charge density increases. Above phase transition temperature, mesoscopic structure of poly(NIPAM-co-NaAMPS) varies from network of physical gel to viscoelastic liquid containing branched aggregates with increase of charge density, indicating increasing hindrance to intra/inter-chain association due to electrostatic repulsion. On a molecular level, poly(NIPAM-co-NaAMPS) exhibits distinctive microdynamic sequence of dehydration during phase transition, in contrast to neutral PNIPAM. In particular, sulfonate groups decouple the cooperative dehydration of alkyl and carbonyl groups, resulting in their distinctive phase transition temperature as well as temperature range. In analogy to hydration of proteins, it is proposed that the microdynamic sequence, implying the hydration stability of each group, is closely related to the density of hydration layer as well as influence of electrostatic field generated by charged groups. For poly(NIPAM-co-AMPS) with charge density of 3%, there still remains 72.3% of hydrogen bonds between carbonyl group and water at 60 °C, meanwhile a highly hydrated network forms with network strands 1–2 times as long as the copolymer chain length.     

pH/temperature sensitive poly(ethylene glycol)-based biodegradable polyester block copolymer hydrogels

Novel pH and temperature sensitive biodegradable block copolymers composed of poly(ethylene glycol) (PEG), polyglycolide (GA), ?-caprolactone (CL) and sulfamethazine oligomers (OSMs) were synthesized by ring opening polymerization and 1,3-dicyclohexyl-carbodiimide (DCC) mediated coupling reactions. Their physicochemical properties in aqueous media were characterized by ¹H NMR spectroscopy and gel permeation spectroscopy. The sol-gel phase transition behavior of OSM-PCGA-PEG-PCGA-OSM block copolymers was investigated both in solution and injection to PBS buffer at pH 7.4 and 37 °C. Aqueous solutions of OSM-PCGA-PEG-PCGA-OSM changed from a sol to a gel phase with increasing temperature and decreasing pH. The sol-gel transition properties of these block copolymers are influenced by the hydrophobic/hydrophilic balance of the copolymers, block length, hydrophobicity, stereoregularity of the hydrophobic components within the block copolymer, and the ionization of the pH functional groups in the copolymer, which depends on the environmental pH. Degradation of the triblock and pentablock copolymers at 37 °C (pH 7.4), and at 0 °C and 5 °C both at pH 8.0, was investigated. It was demonstrated here using the in vitro test method, that the anticancer agent paclitaxel (PTX) could be loaded and released by the pH and temperature sensitive OSM-PCGA-PEG-PCGA-OSM block copolymer, such that this could be used as a suitable matrix for subcutaneous injection in drug delivery systems.     

Microscopic implication of rapid shrinking of comb-type grafted poly(N-isopropylacrylamide) hydrogels

The shrinking mechanism of comb-type grafted poly(N-isopropylacrylamide) gel was investigated by small-angle X-ray scattering (SAXS). The SAXS reveals that the microdomain structure with characteristic spacing of 460 Å is developed in the comb-type grafted poly(N-isopropylacrylamide) gel during the shrinking process. These observations suggest that the freely mobile characteristics of the grafted chains are expected to show the rapid dehydration to make tightly packed globules with temperature, followed by the subsequent hydrophobic intermolecular aggregation of the dehydrated graft chains. The dehydrated grafted chains created the hydrophobic cores, which enhance the hydrophobic aggregation of the networks. These aggregations of the NIPA chains contribute to an increase in void volume, which allow the gel having a pathway of water molecules by the phase separation.     

A study of hydrogel thermal-dynamics using Fourier transform infrared spectrometer

A rapid and reliable method was presented for studying hydrogel dynamics/kinetics. Two temperature-sensitive hydrogels, poly-N-isopropylacrylamide (poly(NIPAAm)) and the copolymer of N,N-diethylacrylamide and sodium methacrylate (molar ratio=97:3, poly(NDEAAm-co-MAA)) were synthesized. The thermal-behaviors of the gels were studied through the absorbance intensities of both swollen water and gel frame components, and the peak positions of amide band along heating/cooling pathways under dynamic Fourier transform infrared (FTIR) probing. The results showed that the lower critical solution temperature (LCST) of poly(NIPAAm) is about 33-35 °C, which is consistent with reported value of ∼34 °C. Compared to poly(NIPAAm), poly(NDEAAm-co-MAA) has relatively continuous volume phase transition, starting at ∼35 °C and a better thermal-reversibility with similar swelling and deswelling profiles over a larger temperature range (10-80 °C for poly(NDEAAm-co-MAA) vs. 10-33 °C for poly(NIPAAm)). The H-bonding water along phase transition was also studied, showing a less reversibility of poly(NIPAAm) compared to poly(NDEAAm-co-MAA). In addition, FTIR spectrometer was also used to study the volume changes of poly(NDEAAm-co-MAA) under variations in environmental salinity.     

Synthesis and thermo-responsive behavior of fluorescent labeled microgel particles based on poly(N-isopropylacrylamide) and its related polymers

Poly(N-isopropylacrylamide) (PNIPAM) microgel particles labeled with 3-(2-propenyl)-9-(4-N,N-dimethylaminophenyl)phenanthrene (VDP) as an intramolecular fluorescent probe were prepared by emulsion polymerization. The thermo-responsive behavior of the VDP-labeled PNIPAM microgel particles dispersed in water was studied by turbidimetric and fluorescence analyses. The transition temperature of the VDP-labeled PNIPAM microgel particles in water determined by turbidimetric analysis was ca. 32.5 °C. The wavelength at the maximum fluorescence intensity of the VDP units linked directly to the microgel particles dramatically blue-shifted around the transition temperature. In addition it gradually blue-shifted even below the transition temperature where there was no change observed in the turbidity. These findings suggest that the gradual shrinking of microgel particles occurs with increasing temperature and the subsequent dramatic shrinking results in the increasing in the turbidity. The transition temperatures of VDP-labeled poly(N-n-propylacrylamide) and poly(N-isopropylmethacrylamide) microgel particles determined by turbidimetric analysis were ca. 23 and ca. 42.5 °C, respectively, and their thermo-responsive behavior was similar to that for the VDP-labeled PNIPAM system. In these three systems the microenvironments around the fluorescent probes above the transition temperatures became more hydrophobic than those below the transition temperature, and the estimated values of microenvionmental polarity around the VDP units on their collapsed states were almost the same.     

Hydroxyl end-functionalized poly(2-isopropyl oxazoline)s used as nano-sized colloidal templates for preparation of hollow polymeric nanocapsules

Hollow polymeric nanocapsules with a thermosensitive membrane are prepared and characterized. They reversibly change their dimensions during temperature variations below and above the transition of the membrane. The nanocapsules were prepared by three steps: (i) well-defined mesoglobules prepared from an LCST polymer (hydroxyl end functionalized poly(2-isopropyl-2-oxazoline), PiPOZ-OH) were coated with a thermo-sensitive cross-linked shell formed via seeded radical copolymerization of N-isopropylacrylamide (NIPAM) and N,N′-bis-methylene acrylamide to produce core–shell nanoparticles (ii), which were subjected to extensive dialysis below the LCSTs of both the core-forming PiPOZ-OH and shell-forming PNIPAM to remove the core (iii). The use of a core-forming polymer of low molecular weight (<8900 g mol⁻¹), narrow dispersity (<1.15) and relatively low T_g (52–68 °C) is beneficial as far as the effectiveness of the removal of the cores is concerned. The inherent immiscibility between PiPOZ-OH and PNIPAM as well as the specific raspberry-like structure of the core–shell particles also contributed for enhancement of the core removal effectiveness.     

Synthesis and thermally responsive characteristics of dendritic poly(ether-amide) grafting with PNIPAAm and PEG

A series of thermally responsive dendritic core-shell polymers were prepared based upon dendritic poly(ether-amide) (DPEA), modified with carboxyl end-capped linear poly(N-isopropylacrylamide) (PNIPAAm-COOH) or both PNIPAAm-COOH and carboxyl end-capped methoxy polyethylene glycol (PEG-COOH) in different ratios via an esterification process to obtain DPEA-PNIPAAm or DPEA-PNIPAAm-PEG. Their molecular structures were verified by gel permeation chromatography, and ¹H NMR and FTIR spectroscopy. The temperature-dependent characteristics study has revealed that DPEA-PNIPAAm exhibits a lower critical solution temperature (LCST) of about 34 °C, whereas DPEA-PNIPAAm-PEG polymers with the PNIPAAm/PEG ratio of about 1.0 and 0.4 possess about 36 °C and 39 °C, respectively, compared with 32 °C for homopolymer PNIPAAm. The critical aggregation temperature was investigated using fluorescence excitation spectrum of pyrene as a sequestered guest molecule based upon the sharp increase of the I₃₃₈/I₃₃₃ value.     

Magnetic core-bilayer shell nanoparticle: A novel vehicle for entrapmentof poorly water-soluble drugs

We are herein reporting a synthesis of indomethacin-loaded bilayer-surface magnetite nanoparticles and their releasing behavior. The particles were first stabilized with oleic acid as a primary surfactant, followed by poly(ethylene glycol) methyl ether-poly(?-caprolactone) (mPEG-PCL) amphiphilic block copolymer as a secondary surfactant to form nanoparticles with hydrophobic inner shell and hydrophilic corona. mPEG-PCL copolymers with systematically varied molecular weights of each block (2000-2000, 2000-10,000, 5000-5000 and 5000-10,000 g/mol, respectively) were synthesized via a ring-opening polymerization of ?-caprolactone using mPEG as a macroinitiator. The particles were 9 nm in diameter and exhibited superparamagnetic behavior at room temperature with saturation magnetization (M_s) about 35 emu/g magnetite. Percent of magnetite and the copolymers in the complexes were determined via thermogravimetric analysis (TGA). The effect of mPEG and PCL block lengths in the copolymer-magnetite complex on the properties of the particles, e.g. particle size, magnetic properties, stability in water, drug entrapping and loading efficiency and its releasing behavior were investigated. This novel magnetic nanocomplex might be suitable for use as an efficient drug delivery vehicle with tunable drug-released properties.     

Temperature-sensitive and highly water-soluble titanate nanotubes

Water-soluble titanate nanotubes (TNTs) with temperature-responsive shells were synthesized by grafting poly(N-isopropylacrylamide) (PNIPAAm) from TNTs via surface atom transfer radical polymerization (ATRP) using ATRP agent functionalized TNTs as macroinitiator. Proton Nuclear magnetic resonance spectroscopy (¹H NMR), Fourier-transform infrared (FT-IR) and thermogravimetric analyses (TGA) results prove the successful graft of PNIPAAm chains from TNTs. TGA shows that the amount of PNIPAAm grown from the TNTs increased with the increase of monomer/initiator ratio. Transmission electron microscope (TEM) measurements displays the obtained TNTs-g-PNIPAAm nanohybrids have a core-shell structure of TNT cores and PNIPAAm shells. In addition, the functional nanotubes demonstrate a reversible low critical solution temperature (LCST) transition with the increase of solution temperature. The synthetic method presented here can also be extended to graft other stimuli responsive polymers from TNTs.     

Novel thermo-responsive membranes composed of interpenetrated polymer networks of alginate-Ca and poly(N-isopropylacrylamide)

In this work, interpenetrated polymer networks (IPN) composed of alginate-Ca²⁺ and poly(N-isopropylacrylamide), PNIPAAm, were synthesized and their water uptake capability was measured at temperatures from 25 to 40 °C and compared to that of pure alginate-Ca²⁺ hydrogels without PNIPAAm. A sharp decrease of WU was observed when IPN hydrogels are heated above 32-33 °C. The phenomenon is associated to a drastic shrinking of hydrogels. At temperatures above 32 °C the PNIPAAm chains collapse, contracting their network and pulling back the alginate-Ca²⁺ network. The rate of shrinking depends of the heating rate. The phenomenon is more effective and faster in IPN containing lower amount of alginate-Ca²⁺. The shrunken IPN hydrogels can be re-swollen but the expansion is slower than the shrinking. The diffusion of Orange II dye through the membrane of IPN hydrogels decreases if the temperature is raised up to 35 °C. The shrinking results in a decrease of the average pores size that makes more difficult the diffusion of Orange II. The average pore size was evaluated in several stages by analysis of SEM micrographs of freeze dried samples: 102.0±14.3 μm at 25 °C, 15.7±5.4 μm at 33 °C and 0.4±0.3 μm at 40 °C. Below the LCST of PNIPAAm, the IPN hydrogels exhibit a morphology characterized by open pores but above the LCST their surface becomes more regular and compact. As a consequence, an increase of the apparent activation energy for permeability, , of Orange II is measured.     

Cyclodextrin based hydrogels: Inclusion complex formation and micellization of adamantane and cholesterol grafted polymers

Inclusion complex formation between β-cyclodextrin (β-CD) and suitable guest molecules has frequently been exploited to design self-assembled polymer networks. In this paper, we report on hydrogels composed of eight-armed poly(ethylene glycol) (PEG) grafted with β-CD (8armPEG20k-CD), adamantane (8armPEG20k-ad) or cholesterol (8armPEG20k-chol). Mixtures of 8armPEG20k-CD and 8armPEG20k-ad showed viscous behavior (G″ > G′); 8armPEG20k-CD and 8armPEG20k-chol formed elastic hydrogels (G′ > G″). To study the interaction of adamantane and cholesterol grafted PEG with β-CD, linear model compounds (mPEG5k-ad and mPEG5k-chol) were synthesized. Isothermal titration calorimetry (ITC) experiments showed a higher association constant for inclusion complexes formed with mPEG5k-chol (47,000 ± 1650) than for those formed with mPEG5k-ad (30,000 ± 900). Fluorescence spectroscopy and dynamic light scattering (DLS) measurements further showed the ability of mPEG5k-chol to self-assemble into micelles. Self-assembly of 8armPEG20k-chol further increased the strength of the formed hydrogels. Altogether, this study contributes to a better understanding of cyclodextrin based biomaterials.