Showing papers by "Zhiyuan Zhong published in 2007"

Novel in situ forming, degradable dextran hydrogels by Michael addition chemistry : Synthesis, rheology, and degradation

Abstract: Various vinyl sulfone functionalized dextrans (dex-VS) (Mn,dextran = 14K or 31K) with degrees of substitution (DS) ranging from 2 to 22 were conveniently prepared by a one-pot synthesis procedure at room temperature. This procedure involved reaction of a mercaptoalkanoic acid with an excess amount of divinyl sulfone yielding vinyl sulfone alkanoic acid, followed by conjugation to dextran using N,N‘-dicyclohexylcarbodiimide (DCC)/4-(dimethylamino)pyridinium 4-toluenesulfonate (DPTS) as a catalyst system. By using two different mercaptoalkanoic acids, 3-mercaptopropionic acid (1a) and 4-mercaptobutyric acid (1b), dex-VS conjugates with either an ethyl spacer (denoted as dex-Et-VS) or a propyl spacer (denoted as dex-Pr-VS) between the thioether and ester groups were obtained. Linear and four-arm mercaptopoly(ethylene glycol) (Mn = 2.1K) with two or four thiol groups (denoted as PEG-2-SH and PEG-4-SH, respectively) were also prepared. Hydrogels were rapidly formed in situ under physiological conditions by Michael type addition upon mixing aqueous solutions of dex-VS and multifunctional PEG-SH at a concentration of 10−20% w/v. The gelation time ranged from 0.5 to 7.5 min, depending on the DS, concentration, dextran molecular weight, and PEG-SH functionality. Rheological studies showed that these dextran hydrogels are highly elastic. The storage modulus increased with increasing DS, concentration, and dextran molecular weight, and hydrogels with a broad range of storage moduli from 3 to 46 kPa were obtained. Swelling/degradation studies revealed that these dextran hydrogels have a low initial swelling and are degradable under physiological conditions. The degradation time varied from 3 to 21 days depending on the DS, concentration, dextran molecular weight, and PEG-SH functionality. Interestingly, dex-Pr-VS hydrogels showed prolonged degradation times, but otherwise similar properties compared to dex-Et-VS hydrogels. The hydrolysis of the linker ester bonds of the dex-VS conjugates under physiological conditions was confirmed by 1H NMR. The results showed that the hydrolysis kinetics were independent of the DS and the dextran molecular weight. Therefore, the degradation rate of these hydrogels can be precisely controlled.

Rapidly in Situ Forming Biodegradable Robust Hydrogels by Combining Stereocomplexation and Photopolymerization

Abstract: Our previous studies have shown that stereocomplexed hydrogels can be rapidly formed in vitro as well as in vivo upon mixing aqueous solutions of eight-arm poly(ethylene glycol)−poly(l-lactide) (PEG−PLLA) and poly(ethylene glycol)−poly(d-lactide) (PEG−PDLA) star block copolymers. In this study, stereocomplexation and photopolymerization are combined to yield rapidly in situ forming robust hydrogels. Two types of methacrylate-functionalized PEG−PLLA and PEG−PDLA star block copolymers, PEG−PLLA−MA and PEG−PDLA−MA, which have methacrylate groups at the PLA chain ends and PEG−MA/PLLA and PEG−MA/PDLA, which have methacrylate groups at the PEG chain ends, were designed and prepared. Results showed that stereocomplexed hydrogels could be rapidly formed (within 1−2 min) in a polymer concentration range of 12.5−17.5% (w/v), in which the methacrylate group hardly interfered with the stereocomplexation. When subsequently photopolymerized, these hydrogels showed largely increased storage moduli as compared to the corresponding hydrogels that were cross-linked by stereocomplexation or photopolymerization only. Interestingly, the storage modulus of stereocomplexed−photopolymerized PEG−PLA−MA hydrogels increased linearly with increasing stereocomplexation equilibration time prior to photopolymerization (from ca. 6 to 32 kPa), indicating that stereocomplexation aids in photopolymerization. Importantly, photopolymerization of stereocomplexed hydrogels could take place at very low initiator concentrations (0.003 wt %). Swelling/degradation studies showed that combining stereocomplexation and photopolymerization yielded hydrogels with prolonged degradation times as compared to corresponding hydrogels cross-linked by photopolymerization only (3 vs 1.5 weeks). Stereocomplexed−photopolymerized PEG−MA/PLA hydrogels degraded much slower than corresponding PEG−PLA−MA hydrogels, with degradation times ranging from 7 to more than 16 weeks. Therefore, combining stereocomplexation and photopolymerization is a novel approach to obtain rapidly in situ forming robust hydrogels.

Ring‐opening polymerization of substituted ε‐caprolactones with a chiral (salen) AlOiPr complex

Abstract: The ring-opening polymerization (ROP) of -caprolactone (-CL), 4-methyl--caprolactone (4-MeCL), and 6-methyl--caprolactone (6-MeCL) with a single-site chiral initiator, R,R-(salen) aluminum isopropoxide (R,R-[1]), was investigated. The kinetic data for the ROP of the three monomers at 90° in toluene corresponded to first-order reactions in the monomer and propagation rate constants of k-CL > k4-MeCL k6-MeCL. A notable stereoselectivity with a preference for the R-enantiomer was observed in the ROP of 6-MeCL with R,R-[1], whereas for 4-MeCL, no stereoselectivity was found

Morphology of a highly asymmetric double crystallizable poly(ε-caprolactone-b-ethylene oxide) block copolymer

Abstract: The morphology of a highly asymmetric double crystallizable poly(epsilon-caprolactone-b-ethylene oxide) (PCL-b-PEO) block copolymer has been studied with in situ simultaneously small and wide-angle x-ray scattering as well as atomic force microscopy. The molecular masses Mn of the PCL and PEO blocks are 24 000 and 5800, respectively. X-ray scattering and rheological measurements indicate that no microphase separation occurs in the melt. Decreasing the temperature simultaneously triggers off a crystallization of PCL and microphase separation between the PCL and PEO blocks. Coupling and competition between microphase separation and crystallization results in a morphology of PEO spheres surrounded by PCL partially crystallized in lamella. Further decreasing temperature induces the crystallization of PEO spheres, which have a preferred orientation due to the confinements from hard PCL crystalline lamella and from soft amorphous PCL segments in different sides. The final morphology of this highly asymmetric block copolymer is similar to the granular morphology reported for syndiotactic polypropylene and other (co-) polymers. This implies a similar underlying mechanism of coupling and competition of various phase transitions, which is worth further exploration

Poly(ferrocenylsilane)-block-Polylactide Block Copolymers

Abstract: A PFS/PLA block copolymer was studied to probe the effect of strong surface interactions on pattern formation in PFS block copolymer thin films. Successful synthesis of PFS-b-PLA was demonstrated. Thin films of these polymers show phase separation to form PFS microdomains in a PLA matrix, and ultrathin films (<5 nm) formed SINPATs on silicon and mica. The SINPATs consisted of strongly surface-adsorbed PLA blocks on top of which the PFS blocks dewetted into sphere-like features. The lateral spacing between these features was regular, and was typically much larger than the length scale associated with regular block copolymer phase separation.

Stereo Photo Hydrofel, a Process of Making Said Stereo Photo Hydrogel, Polymers for Use in Making Such Hydrogel and a Pharmaceutical Comprising Said Polymers

Abstract: The Invention relates to a stereo photo hydrogel formed by stereo complexed and photo cross-linked polymers, which polymers comprise at least two types of polymers having at least one hydrophilic component, at least one hydrophobic mutually stereo complexing component, and at least one of the types comprises at least one photo cross-linkable component, to a process of making stereo photo hydrogel comprising the steps of a. providing a mixture of at least two types of polymers having at least one hydrophilic component, at least one hydrophobic mutually stereo complexing component and at least one of the types comprises at least one photo cross-linkable component; b. stereo complexing the two types of polymers, thereby forming a stereo complexed hydrogel; and c. photo cross-linking the stereo complexed hydrogel using visible or UV irradiation, thereby forming the stereo photo hydrogel, to such polymers for use in such hydrogel, and to a pharmaceutical kit comprising same.