Haoya Han

Chitosan cross-linked poly(acrylic acid) hydrogels: drug release control and mechanism

Chitosan has been used to cross-link poly(acrylic acid) to give three pH-sensitive hydrogels designed to control the release of the drugs amoxicillin and meloxicam. The extent of cross-linking and solution pH was found to dominate the swelling behavior of these hydrogels as shown by scanning electron microscopy and swelling time dependencies. The rates of release of amoxicillin and meloxicam from the loaded hydrogels increased with increase in pH consistent with the extent of hydrogen bonding between hydrogel components and between the hydrogel and the drugs being important determinants of release rate. Both the Korsemeyer-Peppas and Weibull models fitted release data consistent with drug release occurred through a combination of drug diffusion and hydrogel relaxation processes. These hydrogels appear to provide an ideal basis for controlled drug delivery systems.

Protein Immobilization onto Cationic Spherical Polyelectrolyte Brushes Studied by Small Angle X-ray Scattering

The immobilization of bovine serum albumins (BSA) onto cationic spherical polyelectrolyte brushes (SPB) consisting of a solid polystyrene (PS) core and a densely grafted poly(2-aminoethyl methacrylate hydrochloride) (PAEMH) shell was studied by small-angle X-ray scattering (SAXS). The observed dynamics of adsorption of BSA onto SPB by time-resolved SAXS can be divided into two stages. In the first stage (tens of milliseconds), the added proteins as in-between bridge instantaneously caused the aggregation of SPB. Then BSA penetrated into the brush layer driven by electrostatic attractions, and reached equilibrium in the second stage (tens of seconds). The amount of BSA immobilized onto brush layer reached the maximum when pH was increased to about 6.1 and BSA concentration to 10 g/L. The cationic SPB were confirmed to provide stronger adsorption capacity for BSA compared to anionic ones.

Enhancement of enzymatic activity by magnetic spherical polyelectrolyte brushes: a potential recycling strategy for enzymes.

Interactions between amyloglucosidase and magnetic spherical polyelectrolyte brushes (MSPB) were studied by turbidimetric titration, which reveals reversible and tunable behaviors of pH-dependent enzyme-SPB binding. Quantitative thermodyanmic parameters including binding affinity and stoichiometry between enzyme and SPBs were further measured by isothermal titration calorimetry (ITC). A large amount of enzyme can be loaded in MSPB without loss of MSPB stability. We demonstrated that the enzymatic activity of amyloglucosidase bound in MSPB could be greatly enhanced (catalytic reaction rate, k(bound) = 1.36k(free)) compared to free enzyme acitivity in solution. This is tremendous improvement from other carrier systems that usually lead to a significant decrease of enzymatic activity. Both the high enzyme loading capacity and the enhancement of the catalytic activity probably arise from the Coulombic interactions between the enzyme and MSPB. These findings provide a practical strategy for enhancement of enzyme activity and enzyme recycling by MSPB.

Modification of Spherical Polyelectrolyte Brushes by Layer-by-Layer Self-Assembly as Observed by Small Angle X-ray Scattering

Multilayer modified spherical polyelectrolyte brushes were prepared through alternate deposition of positively charged poly(allylamine hydrochloride) (PAH) and negatively charged poly-l-aspartic acid (PAsp) onto negatively charged spherical poly(acrylic acid) (PAA) brushes (SPBs) on a poly(styrene) core. The charge reversal determined by the zeta potential indicated the success of layer-by-layer (LBL) deposition. The change of the structure during the construction of multilayer modified SPBs was observed by small-angle X-ray scattering (SAXS). SAXS results indicated that some PAH chains were able to penetrate into the PAA brush for the PAA-PAH double-layer modified SPBs whereas part of the PAH moved towards the outer layer when the PAsp layer was loaded to form a PAA-PAH-PAsp triple-layer system. The multilayer modified SPBs were stable upon changing the pH (5 to 9) and ionic strength (1 to 100 mM). The triple-layer modified SPBs were more tolerated to high pH (even at 11) compared to the double-layer ones. SAXS is proved to be a powerful tool for studying the inner structure of multilayer modified SPBs, which can establish guidelines for the a range of potential applications of multilayer modified SPBs.

Tunable immobilization of protein in anionic spherical polyelectrolyte brushes as observed by small-angle X-ray scattering

Tunable immobilization of bovine serum albumins (BSA) onto anionic spherical polyelectrolyte brushes (SPB) by changing BSA concentration, pH, and ionic strength was mainly observed by small-angle X-ray scattering (SAXS). Change of the BSA amount immobilized in SPB can be determined by SAXS which was confirmed by UV spectroscopy, and SAXS is the unique method to “see” the distribution of BSA in SPB. More BSA entered into brush layer upon increasing the protein concentration or decreasing the ionic strength of solutions. When pH increased from 3 to 5 (around the isoelectric point of BSA 4.9), more BSA came into the brush inner layer, while the proteins partly moved to the outer layer when pH continued to increase. After pH was higher than 7, most of BSA were desorbed from SPB. SAXS is proved to be a powerful tool to monitor the tunable immobilization and distribution of proteins in SPB.

Core–Shell–Corona Silica Hybrid Nanoparticles Templated by Spherical Polyelectrolyte Brushes: A Study by Small Angle X-ray Scattering

Core-shell-corona silica/polymer hybrid nanoparticles with narrow size distribution were prepared in the template of spherical polyelectrolyte brushes (SPB) which consist of a solid polystyrene (PS) core densely grafted with linear poly(acrylic acid) (PAA) chains. The microstructure of obtained hybrid nanoparticles was studied by small-angle X-ray scattering (SAXS) and in combination with dynamic light scattering (DLS) and transmission electron microscopy (TEM). The generation of silica shell within the brush is confirmed by the significant increase of the electron density in the shell, and the silica shell showed a unique inner-loose-outer-dense structure, whose thickness is pH sensitive but is insensitive to ionic strength as revealed by fitting SAXS data. After dissolving the PS core, hollow silica nanoparticles were obtained and determined by SAXS, which should be ideal carriers for pH-triggered drug delivery. SAXS is confirmed to be a powerful method to characterize the core-shell-corona silica/polymer hybrid and hollow silica nanoparticles.

β-Lactoglobulin (BLG) binding to highly charged cationic polymer-grafted magnetic nanoparticles: effect of ionic strength.

Poly(2-(methacryloyloxy)ethyltrimethyl ammonium chloride) (PMATAC) modified magnetic nanoparticles (NPs) with a high zeta potential of ca. 50mV were synthesized by atom transfer radical polymerization (ATRP). The prepared NPs consist of a magnetic core around 13nm and a PMATAC shell around 20nm attached on the surface of magnetic nanoparticles. Thermodynamic binding parameters between β-lactoglobulin and these polycationic NPs were investigated at different ionic strengths by high-resolution turbidimetry, dynamic light scattering (DLS), and isothermal titration calorimetry (ITC). Both turbidity and ITC show that binding affinities for BLG display a non-monotonic ionic strength dependence trend and a maximum appears at ionic strength of 50mM. Such observation should arise from the coeffects of protein charge anisotropy visualized by DelPhi electrostatic modeling and the strong electrostatic repulsion among highly charged NPs at a variety of ionic strengths.

Characterization of hollow silica-polyelectrolyte composite nanoparticles by small-angle X-ray scattering

Hollow silica–polyelectrolyte composite nanoparticles were prepared using templates of spherical polyelectrolyte brushes which consist of a polystyrene (PS) core and a densely grafted linear poly(acrylic acid) shell. The obtained hollow particles were systematically studied by small-angle X-ray scattering (SAXS) in combination with other characterization methods such as transmission electron microscopy and dynamic light scattering. The hollow structure formed by dissolving the PS core was confirmed by the reduction of electron density to zero in the cavity through fitting SAXS data. SAXS revealed both the inward and outward expansions of the hollow silica–polyelectrolyte composite particles upon increasing pH from 3 to 9, while further increasing pH led to the partial dissolution of silica layer and even destruction of the hollow structure. SAXS was confirmed to be a unique and powerful characterization method to observe hollow silica nanoparticles, which should be ideal candidates for controlled drug delivery.

Spherical polyelectrolyte nanogels as templates to prepare hollow silica nanocarriers: observation by small angle X-ray scattering and TEM

Hollow silica nanoparticles were prepared through generating a silica layer in spherical polyelectrolyte nanogels (SPN), which consisted of a solid core of polystyrene (PS) and a shell of crosslinked poly(acrylic acid) (PAA), followed by removing the PS core via solvent dissolution. Small angle X-ray scattering (SAXS) in combination with TEM were employed to observe SPN, silica–polymer composite, and hollow silica nanoparticles. It was confirmed that SAXS is a powerful method to monitor the generation of silica layer in SPN. The density and thickness of generated silica layer in SPN were found to be tunable by controlling the crosslinking density of the templates. The porous structure and pH sensitivity of silica layer allowed the obtained hollow silica to be ideal carriers for controlled drug delivery.

Hollow silica–polyelectrolyte composite nanoparticles for controlled drug delivery

The stimulus-responsive drug delivery system has attracted increasing attention due to its ability to enhance therapeutic efficacy and reduce side effects. Herein, a pH and glutathione (GSH) dually responsive drug carrier, hollow silica–-polyelectrolyte composite nanoparticle, was successfully prepared by using a template of spherical polyelectrolyte brush (SPB) which consists of a polystyrene (PS) core and a densely grafted linear poly(acrylic acid) (PAA) shell. The existence of PAA chains and introduction of disulfide bonds in silica framework endow the composite nanoparticles with pH and GSH dually responsive properties which were confirmed by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). With doxorubicin hydrochloride (DOX) as the model drug, the loading content and encapsulation efficiency could reach up to 43% and 96%, respectively. The drug release behavior was investigated under various environments, showing that the drug release rate increased with the decrease in pH value and the increase in GSH concentration. The prepared hollow SiO2–PAA composite nanoparticles possess a great potential as carriers for controlled drug delivery.