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Biomedical subjects

Xian-Zheng Zhang

Publications and source records attributed to Xian-Zheng Zhang.

17 recordsLinked to original sources

Synthesis of novel cholic acid functionalized branched oligo/poly(epsilon-caprolactone)s for biomedical applications.

Novel cholic acid functionalized branched oligo/poly(epsilon-caprolactone)s were synthesized through the ring-opening polymerization of epsilon-caprolactone initiated by cholic acid with hydroxyl groups. The molecular weight of the branched polymers can be adjusted by controlling the feed ratio of the initiator cholic acid to the monomer epsilon-caprolactone. Comparing with linear homopolymer poly(epsilon-caprolactone) (PCL), these branched oligo/poly(epsilon-caprolactone)s show much faster hydrolytic degradation rates, implies that our approach provides a convenient and effective strategy to accelerate degradation of the biodegradable polymers with slow degradation rates such as PCL. The cell culture experiment indicates the incorporation of cholic acid moiety to the polymer chain can improve both cell adherence and proliferation obviously.

Animals↗

Fabrication and characterization of a novel composite PNIPAAm hydrogel for controlled drug release.

Novel composite poly(N-isopropylacrylamide) (PNIPAAm) hydrogels, containing poly(N-isopropylacrylamide)-block-poly(methyl methacrylate) (PNIPAAm-b-PMMA) micelles for sustained drug delivery were prepared and characterized. Various amounts of thermal sensitive PNIPAAm-b-PMMA micelles were incorporated physically into thermosensitive PNIPAAm bulk hydrogel to form composite PNIPAAm hydrogels. The resultant composite hydrogels were characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) for morphological and thermal properties, respectively. The temperature dependence of swelling ratio and response kinetics upon heating or cooling were also investigated to understand the smart properties, that is, temperature-sensitive properties of the composite PNIPAAm hydrogels. These composite PNIPAAm hydrogels exhibited a faster shrinking kinetics than the one of pure PNIPAAm hydrogels. In addition, prednisone acetate, used as model drug, was loaded into the micelles incorporated to the composite PNIPAAm hydrogels. The controlled release behavior of the novel composite PNIPAAm hydrogels at different temperatures (22 and 37 degrees C) was examined.

Acrylic Resins↗

Degradation and drug release property of star poly(epsilon-caprolactone)s with dendritic cores.

A series of star poly(epsilon-caprolactone)s (PCL) with dendritic cores, PAMAM-PCLs, were synthesized through the ring-opening polymerization of epsilon-caprolactone (CL) initiated by poly(amidoamine) dendrimer (PAMAM-OH). By controlling the feed ratio of the macroinitiator PAMAM-OH to the monomer CL, the star polymers with different branch lengths and properties can be obtained. The successful incorporation of PCL sequences onto the PAMAM-OH core was verified by FTIR, 1H NMR, and combined size-exclusion chromatography and multiangle laser light scattering analysis. The in vitro degradation of PAMAM-PCLs was investigated. The results show the hydrolytic degradation rate increases with increasing content of hydrophilic PAMAM-OH core. While the enzymatic degradation rate is affected by two competitive factors, the catalytic effect of Pseudomonas cepacia lipase on the degradation of PCL branches and the hydrophilicity that depends on the polymer composition. Using the PAMAM-PCLs with different molecular weights, the microsphere drug delivery systems with submicron sizes were fabricated using an "ultrasonic assisted precipitation method." The in vitro drug release from these microspheres was investigated.

Biocompatible Materials↗

Self-assembled thermo- and pH responsive micelles of poly(10-undecenoic acid-b-N-isopropylacrylamide) for drug delivery.

An amphiphilic AB block copolymer composed of poly(N-isopropylacrylamide) as a hydrophilic segment and poly(10-undecenoic acid) as a hydrophobic segment was synthesized. Cytotoxicity study of this copolymer exhibited no significant cytotoxicity. The lower critical solution temperature (LCST) of the copolymer was 30.8 degrees C, as determined by the turbidity method. The block copolymer forms micelles in an aqueous medium at the temperature lower than the LCST. Transmission electron microscopy images showed that these micelles were regularly spherical in shape. The micelle size determined by size analysis was around 160 nm. The anti-inflammation drug prednisone acetate was incorporated into the micelles and the release profiles of prednisone acetate showed a dramatic thermoresponsive switching behavior and a unique pH responsive behavior. Moreover, the pH responsive behavior was in relation to the thermoresponsive behavior. That is, the micelles were not pH sensitive at the temperature below the LCST, but the aggregates were pH sensitive at the temperature above the LCST. Based on these results, the thermo- and pH responsive micelles have great potential to be a novel carrier for drug delivery.

Acrylic Resins↗

Thermosensitive Y-shaped micelles of poly(oleic acid-Y-N-isopropylacrylamide) for drug delivery.

A novel thermosensitive amphiphilic copolymer comprised of two hydrophobic poly(oleic acid) (POA) segments and one hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) segment was designed and synthesized. The structure of the copolymer was confirmed as Y-shaped by FTIR, 1H NMR, and SEC-MALLS analysis. A cytotoxicity study shows that the P(OA-Y-NIPAAm) copolymer exhibits good biocompatibility. The copolymer may self-assemble into micelles in water, with the hydrophobic POA segments at the cores of micelles and the hydrophilic PNIPAAm segments as the outer shells. The resulting micelles demonstrate temperature sensitivity with a lower critical solution temperature (LCST) of 31.5 degrees C and a critical micelle concentration (CMC) of 12.6 mg L(-1). Transmission electron microscopy (TEM) shows that the micelles exhibit a nanospheric morphology within a narrow size range of approximately 10-30 nm. A study of controlled release reveals that the self-assembled micelles have great potential as drug carriers.

3T3 Cells↗

Novel stimuli-responsive micelle self-assembled from Y-shaped P(UA-Y-NIPAAm) copolymer for drug delivery.

A new amphiphilic Y-shaped copolymer, comprised of hydrophobic poly(undecylenic acid) (PUA) and hydrophilic poly(N-isopropylacrylamide) (PNIPAAm), was designed and synthesized. A cytotoxicity study revealed that P(UA-Y-NIPAAm) copolymers did not exhibit apparent inhibition impact on the proliferation of cells when the concentration of the copolymer was below 1000 mg/L. Characterization demonstrated that the P(UA-Y-NIPAAm) copolymer is thermosensitive with a lower critical solution temperature (LCST) of 31 degrees C. In water, the P(UA-Y-NIPAAm) copolymer would self-assemble into micelles with a critical micelle concentration (CMC) of 20 mg/L. Self-assembled P(UA-Y-NIPAAm) micelles exhibited a nanospherical morphology of 40 to approximately 80 nm in size. The controlled drug release behavior of the P(UA-Y-NIPAAm) micelles was further investigated, and self-assembled micelles exhibited improved properties in controlled drug release.

3T3 Cells↗

Study on drug release behaviors of poly-alpha,beta-[n-(2-hydroxyethyl)-L-aspartamide]-g-poly(epsilon-caprolactone) nano- and microparticles.

Biodegradable amphiphilic graft copolymers poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide]-g-poly(epsilon-caprolactone) (PHEA-g-PCL) with different branch lengths were synthesized through the ring-opening polymerization of epsilon-caprolactone initiated by the macroinitiator PHEA bearing hydroxyl groups. With use of the graft copolymers with different compositions, nanoparticle drug delivery systems with sizes smaller than 100 nm were prepared by a dialysis method, and microparticle drug delivery systems with sizes smaller than 5 microm were fabricated by a melting-emulsion method. The regularly spherical shapes of the drug-loaded nano- and microparticles were verified by transmission electron microscopy and scanning electron microscopy. In vitro drug release properties of nano- and microparticle drug delivery systems were investigated, with the emphasis on the effects of polymer composition, particle size, and drug-loading content on the release behaviors.

Dialysis↗

Self-assembled thermoresponsive micelles of poly(N-isopropylacrylamide-b-methyl methacrylate).

To achieve a combination of spatial specificity in a passive manner with a stimuli-response targeting mechanism, a temperature-responsive polymeric micelle was prepared using block copolymers of poly(N-isopropylacrylamide-b-methyl methacrylate) (PNIPAAm-b-PMMA). The critical micelle concentration of amphiphilic block copolymers in aqueous solution was determined by fluorescence spectroscopy using pyrene as a fluorescence probe. Transmission electron microscopy images showed that these nanoparticles were regularly spherical in shape. Micelle size determined by size analysis was around 190 nm. The micelles showed reversible dispersion/aggregation in response to temperature cycles through an outer polymer shell lower critical solution temperature (LCST) for PNIPAAm at around 33 degrees C, observed by optical absorbance measurements and dynamic light scattering (DLS). The anti-inflammation drug prednisone acetate was loaded as the model drug in the polymeric nanoparticles. In vitro release behavior of prednisone acetate was investigated, which showed a dramatic thermoresponsive fast/slow switching behavior according to the temperature-responsive structural changes of a micellar shell structure. The reversible and sensitive thermoresponse of this micelle might provide opportunities to construct a novel drug delivery system in conjunction with localized hyperthermia.

Acrylamides↗

Fabrication and characterization of a smart drug delivery system: microsphere in hydrogel.

In this contribution, a novel smart drug delivery system (DDS) consisting of hydroxyl-functionalized glycerol poly(epsilon-caprolactone) (PGCL)-based microspheres and poly(N-isopropylacrylamide) (PNIPAAm) hydrogel was developed for prolonged and sustained controlled drug release. Various amounts PGCL-based microspheres were incorporated physically into temperature sensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel to form the novel DDSs. Resulting DDSs were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and compression modulus measurements to investigate the morphological, thermal, and mechanical properties. The temperature dependence of swelling ratio and response kinetics upon heating or cooling were also investigated to understand the smart properties, i.e., temperature sensitive properties of these DDSs. Finally, ovalbumin (OVA), used as the model drug, was loaded into PGCL-based microspheres to examine and compare the effects of controlled release at different temperature (22 and 37 degrees C) of these novel smart DDSs.

Acrylic Resins↗

Synthesis, characterization and controlled drug release of thermosensitive IPN-PNIPAAm hydrogels.

A method was developed to prepare thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with an interpenetrating polymer network (IPN) structure for the purpose of improving its mechanical properties, response rate to temperature and sustained release of drugs. Although the differential scanning calorimetry data exhibited similarly lower critical solution temperature (LCST) between IPN- and non-IPN-PNIPAAm hydrogels, an increase in the glass transition temperature (Tg) of the IPNs relative to the normal PNIPAAm hydrogel was observed. In addition, the mechanical properties of the IPNs were greatly improved when compared with the normal PNIPAAm hydrogel. The interior morphology of the IPN-PNIPAAm hydrogels was revealed by scanning electron microscopy (SEM); the IPN hydrogels showed a fibrillar-like porous network structure that normal PNIPAAm did not have. Furthermore, by measuring the temperature dependence of the swelling ratio and deswelling kinetics, these IPN hydrogels also exhibited improved intelligent characteristics (e.g., controllable faster response rate) that depended on the composition ratio of the two network components. From the applications viewpoint, the effects of a shrinking-reswelling cycle around the LCST on the properties of the IPN hydrogels were examined to determine if these properties would be stable for potential applications. Bovine serum albumin was chosen as the model protein for examining its release from the IPNs at different temperatures. The release data suggested that an improved controlled release could be achieved by the IPN-PNIPAAm hydrogels without losing their intelligent properties.

Absorption↗

Synthesis and characterization of partially biodegradable and thermosensitive hydrogel.

A partially biodegradable and thermosensitive hybrid hydrogel network (DAN series) based on dextran-allylisocyanate (Dex-AI) and poly(N-isopropylacrylamide) (PNIPAAm) was synthesized via UV photocrosslinking. These hybrid hydrogels were characterized in terms of their chemical structure, thermal, mechanical, morphological and temperature-induced swelling properties. The effect of the composition ratio of Dex-AI to PNIPAAm on such properties were examined. The differential scanning calorimetry data show that this Dex-AI/PNIPAAm hybrid network has an increased lower critical solution temperature (LCST) and glass transition temperature (Tg) with an increase in the Dex-AI content. The interior morphology of these hybrid hydrogels revealed a decreased porous microstructure with an increase in the Dex-AI content in the hybrid network. Furthermore, if the Dex-AI composition became too high, a distinctive network structure with two different microporous structures appeared. The mechanical properties of these hybrid hydrogels also increased with an increase in the Dex-AI content. The temperature dependence of the swelling ratio, the deswelling kinetics as well as the reswelling kinetics was also characterized by gravimetric method. When comparing with a normal PNIPAAm hydrogel, these Dex-AI/PNIPAAm hybrid networks, due to the presence of Dex-AI moiety, also show improved temperature-induced intelligent properties, such as the faster and controllable response dynamics, which may find promising applications in a wide variety of fields, such as biomedical and bioengineering fields.

Absorbable Implants↗

Thermosensitive PNIPAAm cryogel with superfast and stable oscillatory properties.

Through copolymerization/crosslinking in dimethyl sulfoxide (DMSO) at temperature below the melting point of DMSO, we demonstrated a novel poly(N-isopropylacrylamide) (PNIPAAm) hydrogel with regularly oriented micromatrix; the superfast/stable oscillatory hydration-dehydration character of this hydrogel would find wide applications in biomedical field.

Journal Article↗

Thermoresponsive hydrogel with rapid response dynamics.

Intelligent hydrogels, particularly poly(N-isopropylacrylamide) (PNIPAAm)-based hydrogels, have attracted extensive interest because the soft wet hydrogels can change their shapes in response to the small changes of environmental factors like temperature. In order to fully make use of this unique property of PNIPAAm-based hydrogels, the response rates of the PNIPAAm hydrogels have to be improved since the dynamics property is critical to certain applications of this material. In this paper, the thermo-sensitive PNIPAAm hydrogels were successfully synthesized by carrying out the polymerization of N-isopropylacrylamide monomer in vacuum (-100 kPa) at room temperature (22 degrees C). The resultant hydrogel has tremendously improved shrinking rate as well as the large volume changes upon temperature stimulation when comparing with the normal PNIPAAm hydrogel. The SEM micrographs revealed that the improved properties were attributed to the macroporous network structure generated during the synthesis under vacuum.

Journal Article↗

A novel thermo-responsive drug delivery system with positive controlled release.

The model drug, 5-fluorouracil (5-FU) was loaded into the poly(N-isopropylacrylamide) (PNIPA) hydrogel at 25 degrees C, then the drug-loaded, swollen hydrogel sample was carefully enveloped in the dialysis bag to form a novel thermo-responsive drug delivery system (DDS). The concentration of released 5-FU was monitored at 266 nm on the UV spectrophotometer. We found that this novel DDS provides a positive drug release pattern and the drug, 5-FU, was released faster at the increased temperature (37 degrees C, >25 degrees C) than the one at the decreased temperature (10 degrees C, <25 degrees C). This was attributed to the double control of the thermo-sensitivity of the hydrogel matrix and the dialysis membrane. By employing the fast response PNIPA hydrogel instead of the conventional hydrogel in this novel DDS, we can further control the drug release rate and/or drug release amount etc., without changing the positive, thermo-responsive drug release pattern.

Antineoplastic Agents↗

The influence of cold treatment on properties of temperature-sensitive poly(N-isopropylacrylamide) hydrogels.

Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel exhibits a response to external temperature variation and shrinks in volume abruptly as the temperature is increased above its lower critical solution temperature. It has great potential applications in biomedical fields. A rapid response rate is essential, especially when this material is designed as an on-off switch for targeted drug delivery. However, due to the appearance of a thick, dense skin layer on the hydrogel surface during the shrinking process, the deswelling rate of conventional PNIPAAm gels is low. In this article, a novel method is proposed to modify the surface morphology of PNIPAAm gel, in which the swollen gels are frozen at low temperature (-20 degrees C). The scanning electron micrographs revealed that a fishnet-like skin layer appeared on the surfaces of the cold-treated gels. Dramatically rapid deswelling was achieved with the cold-treated gels since the fishnet-like structure with numerous small pores prevented the formation of a dense, thick skin layer during the deswelling process, which commonly occurs in normal PNIPAAm hydrogels. Prolonging the cold treatment from 1 day to 10 days resulted in a slightly higher deswelling rate. Rearrangement of the hydrogel matrix structure during the freezing process might contribute to the formation of the fishnet-like skin layer. The water uptake of the hydrogels increased nearly in proportion to the square root of time, indicating that the reswelling rate of hydrogels was controlled predominantly by water diffusion into the network. However, there were no significant differences in the equilibrated swelling ratio and reswelling kinetics at room temperature (22 degrees C) between normal gels and cold-treated gels, which implied that cold treatment did not change bulk porosity and gel tortuosity much.

Journal Article↗

Synthesis, characterization, and degradation behavior of amphiphilic poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide]-g-poly(epsilon-caprolactone).

A series of biodegradable amphiphilic graft polymers were successfully synthesized by grafting poly(epsilon-caprolactone) (PCL) sequences onto a water-soluble poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA) backbone. The graft copolymers were prepared through the ring-opening polymerization of epsilon-caprolactone (CL) initiated by the macroinitiator PHEA with pendant hydroxyl groups without adding any catalyst. By controlling the feed ratio of the macroinitiator to the monomer, the copolymers with different branch lengths and properties can be obtained. The successful grafting of PCL sequences onto the PHEA backbone was verified by FTIR, 1H NMR, and combined size-exclusion chromatography and multiangle laser light scattering (SEC-MALLS) analysis. The hydrolytic degradation and enzymatic degradation of these graft copolymers were investigated. The results show the hydrolytic degradation rate increases with increasing content of hydrophilic PHEA backbone. While the enzymatic degradation rate is affected by two competitive factors, the catalytic effect of Pseudomonas cepacia lipase on the degradation of PCL branches and the hydrophilicity which depends on the copolymer composition. In situ observation of the degradation under polarizing light microscope (PLM) demonstrates the different degradation rates of different regions in the polymer samples.

Aspartic Acid↗