Synthesis of MPEG-b-PLLA Diblock Copolymers and Their Crystallization Performance with PDLA and PLLA Composite Films.

Methoxy poly(ethylene glycol)-block-poly(L-lactide) (MPEG-b-PLLA) has a wide range of applications in pharmaceuticals and biology, and its structure and morphology have been thoroughly studied. In the experiment, we synthesized MPEG-b-PLLA with different block lengths using the principle of ring-opening polymerization by controlling the amount of lactic acid added. The thermodynamic properties of copolymers and the crystallization properties of blends were studied separately. The crystallization kinetics of PDLA/MPEG-b-PLA and PLLA/MPEG-b-PLA composite films were studied using differential scanning calorimetry (DSC). The results indicate that the crystallization kinetics of composite films are closely related to the amount of block addition. The crystallinity of the sample first increases and then decreases with an increase in MPEG-b-PLLA content. These results were also confirmed in polarized optical microscope (POM) and wide-angle X-ray diffraction (WAXD) tests. When 3% MPEG-b-PLLA was added to the PDLA matrix, the blend exhibited the strongest crystallization performance.

A Temperature and pH Dual-Sensitive Multifunctional Polyurethane with Bacteria-Triggered Antibacterial Activity.

An effective and practical antibacterial strategy is to design multifunctional and stimuli-responsive materials that exhibit antibacterial activity in response to bacterial triggers. In this study, because the metabolism of Staphylococcus aureus (S. aureus) can acidify the surrounding environment and pH level can affect the lower critical solution temperature of temperature/pH dual-sensitive polymers, a monomer containing a temperature-sensitive N-isopropyl amide derivative and pH-sensitive tertiary amine groups is first synthesized. Then, the monomer is copolymerized with a polyurethane chain, and partial tertiary amine groups are quaternized to obtain bactericidal activity. The modified polyurethane exhibits temperature/pH sensitivity, antibacterial adhesion activity, bactericidal activity, and good cytocompatibility. An in situ investigation of bacterial behavior and pH changes in the bacterial suspension during the process confirms that the temperature/pH dual-sensitive polyurethane successfully achieves antibacterial activity though the metabolic activity of S. aureus without external intervention. This design concept provides a new perspective for antibacterial material design.

Recent advances in enhancing stereocomplexation between poly(lactide) enantiomeric chains.

Over the past three decades, its excellent biodegradability and biocompatibility have enabled poly(lactide) (PLA) to be extensively explored as a replacement for oil-based thermoplastics in biomedical and industrial applications. However, PLA homopolymers have "facilitative" limitations such as low mechanical properties, low processing temperatures, slow recrystallization, and insufficient crystallinity, which have usually hindered commercial PLA in industrial and biomedical applications. The formation of stereo-complexation between enantiomeric poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA) chains offers an effective approach to PLA-based engineering materials with improved properties. In this review, we have understandably summarized recent progress in improving the SC crystallization of PLA-based plastics into two aspects, i.e., enantiomeric PLA homopolymers, and enantiomeric PLA-based copolymers. One important point to be noted is that much emphasis is focused on improving SC crystallization by enhancing interactions in the enantiomeric PLA-based copolymers. There is an insightful discussion about the effect of enhanced SC crystallization as well as intermolecular interactions between PLLA and PDLA chains in various stereocomplexable systems. Most importantly, this review starts with the basic understanding of SC crystallization and further elaborates on the rational mechanism of enhanced SC crystallization to provide a broad idea for broadening the road toward PLA-based materials.

Role of the Branched PEG-b-PLLA Block Chain in Stereocomplex Crystallization and Crystallization Kinetics for PDLA/MPEG-b-PLLA-g-glucose Blends with Different Architectures.

The isothermal crystallization behavior and corresponding morphology evolution of poly(d-lactic acid) (PDLA) blends with PLLA6.7k or MPEG-b-PLLA6.7k-g-glucose with different architectures and different PLLA-grafted copolymer contents were investigated. The formation of stereocomplexes (SCs) in between the chain branched structure of MPEG-b-PLLA6.7k-g-glucose and PDLA chains acting as the physical crosslinking points slows down the motion of PDLA chains, but the SCs could act as a heterogeneous nucleating agent for the late formation of homocrystals (HCs) in the blend system, accelerating the crystallization kinetics of HCs through enhancing the nucleation density. For PDLA/MPEG-b-PLLA6.7k-g-glucose blends, the mobility of SCs in the blend system and the nucleation density of SCs in the blends exhibit oppositional behavior during the isothermal crystallization at a Tc of 130 °C. The evolution of the crystal growth and structure during the isothermal crystallization process by rheometry has revealed the interesting role of the branched chains of MPEG-b-PLLA6.7k-g-glucose in the mechanism of the crystallization in PDLA blends.

Competitive Mechanism of Stereocomplexes and Homocrystals in High-Performance Symmetric and Asymmetric Poly(lactic acid) Enantiomers: Qualitative Methods.

To systematically explore the critical contributions of both molecular weights and crystallization temperature and chain length and molar ratios to the formation of stereocomplexes (SCs), our group quantitatively prepared a wide MW range of symmetric and asymmetric poly(lactic acid) (PLA) racemic blends, which contains L-MW PLLA with M n > 6k g/mol. The crystallinity and relative fraction of SCs increase with T c, and the SCs are exclusively formed at T c > 180 °C in M/H-MW racemic blends. When MWs of one of the enantiomers are over 6k and less than 41k, multiple stereocomplexation is clear in the asymmetric racemic blends and more ordered SCs form with less entanglement or the amorphous region compared to those for the MW of the enantiomers over 41k in the symmetric/asymmetric enantiomers. When the MW of the blends is more than 41k, SCs and homocrystals (HCs) coexist in the symmetric enantiomers and the multicomplexation can restrict the asymmetric enantiomers. This study provides a deep comprehensive insight into the stereocomplex crystallization mechanism of polymers and provides a reference value for future research attempting to prepare stereocomplex materials.

In situ real-time investigation of Staphylococcus aureus on hemisphere-patterned polyurethane films.

Surface patterning is a promising approach to prevent bacterial adhesion and biofilm formation without the concerns of antimicrobial resistance. To determine the parameters of a patterned surface that can affect bacterial behavior, a sphere-like coccus (Staphylococcus aureus) was investigated on a series of polyurethane films with ordered hemisphere patterns. The bacterial retention data in a growth medium indicated that the surface patterns significantly decreased bacterial adhesion and proliferation. The most notable effects were observed with the 2 µm-pattern as well as the patterned polycaprolactone and polystyrene films, and the accessible contact area of the polyurethane films, surface wettability, and spatial confinement, did not show an influence. An optical microscope with a modified incubation cell was used for in situ real-time observations of bacterial colonization, proliferation, and migration. Based on appropriate statistical analyses, it was concluded that topographical geometry played a dominant role. In combination with the retention assessment in a nongrowth medium, it was found that pattern-mediated inhibition of biofilm formation was mainly achieved by affecting bacterial proliferation rather than adhesion. This study provides new insight for designing biofilm-resistant biomimetic materials.

Synthesis and Properties of Nitrogen-Doped Carbon Quantum Dots Using Lactic Acid as Carbon Source.

Nitrogen-doped carbon quantum dots (N-CQDs) were synthesized in a one-step hydrothermal technique utilizing L-lactic acid as that of the source of carbon and ethylenediamine as that of the source of nitrogen, and were characterized using dynamic light scattering, X-ray photoelectron spectroscopy ultraviolet-visible spectrum, Fourier-transformed infrared spectrum, high-resolution transmission electron microscopy, and fluorescence spectrum. The generated N-CQDs have a spherical structure and overall diameters ranging from 1-4 nm, and their surface comprises specific functional groups such as amino, carboxyl, and hydroxyl, resulting in greater water solubility and fluorescence. The quantum yield of N-CQDs (being 46%) is significantly higher than that of the CQDs synthesized from other biomass in literatures. Its fluorescence intensity is dependent on the excitation wavelength, and N-CQDs release blue light at 365 nm under ultraviolet light. The pH values may impact the protonation of N-CQDs surface functional groups and lead to significant fluorescence quenching of N-CQDs. Therefore, the fluorescence intensity of N-CQDs is the highest at pH 7.0, but it decreases with pH as pH values being either more than or less than pH 7.0. The N-CQDs exhibit high sensitivity to Fe3+ ions, for Fe3+ ions would decrease the fluorescence intensity of N-CQDs by 99.6%, and the influence of Fe3+ ions on N-CQDs fluorescence quenching is slightly affected by other metal ions. Moreover, the fluorescence quenching efficiency of Fe3+ ions displays an obvious linear relationship to Fe3+ concentrations in a wide range of concentrations (up to 200 µM) and with a detection limit of 1.89 µM. Therefore, the generated N-CQDs may be utilized as a robust fluorescence sensor for detecting pH and Fe3+ ions.

Surface Modification of Poly(l-lactic acid) through Stereocomplexation with Enantiomeric Poly(d-lactic acid) and Its Copolymer.

Poly(l-lactic acid) with high molecular weight was used to prepare PLLA films by means of the solvent casting technique. Poly(d-lactic acid) (PDLA) and poly(d-lactic acid-co-glucose) copolymer (PDLAG) with a low molecular weight were synthesized from d-lactic acid and glucose through melt polycondensation. PLLA films were immersed in PDLA or PDLAG solution to prepare surface-modified PLLA films. The modified PLLA film presented stereocomplex crystal (SC) on its surface and homogeneous crystals (HC) in its bulk. The HC structure and surface morphology of modified PLLA films were obviously damaged by PDLA or PDLAG solution. With increasing immersion time, the PLLA films modified by PDLA decreased both the HC and SC structure, while the PLLA films modified by PDLAG increased the SC structure and decreased the HC structure. Hydrophilic glucose residues of PDLAG on the surface would improve the hydrophilicity of surface-modified PLLA films. Moreover, the hydrophilicity of glucose residues and the interaction of glucose residues with lactic acid units could retard HC destruction and SC crystallization, so that PLLA films modified by PDLAG possessed lower melting temperatures of HC and SC, the crystallinity of SC and the water contact angle, compared with PDLAG-modified PLLA films. The SC structure could improve the heat resistance of modified PLLA film, but glucose residues could block crystallization to promote the thermal degradation of PLA materials. The surface modification of PLLA films will improve the thermal stability, hydrophilicity and crystallization properties of PLA materials, which is essential in order to obtain PLA-based biomaterials.

Small diameter blood vessels with controllable micropore structure induced by centrifugal force for improved endothelialization.

The micropore structure is prerequisite for fast and durable endothelialization of artificial small diameter blood vessels (ASDBVs). Although some methods, such as salt leaching, coagulation, and electrospinning, have been developed to construct micropores for ASDBVs, the uncontrollability of the structure and the complicated procedures of the process are still the issues to be concerned about. In this study, a compact device based on the principle of centrifugal force is established and used to prepare polyurethane (PU) ASDBVs with micropore structures by blasting different porogens. It is found that the glass beads could construct micropores with regular round shape, uniform distribution, and controllable size (60-350 µm), which significantly improves the endothelialization of PU-based ASDBVs, especially when the pore size is about 60 µm. This method is easy-accessible and wide-applicable, which provides a new pathway for the research and development of ASDBVs.

Preparation and Properties of Stereocomplex of Poly(lactic acid) and Its Amphiphilic Copolymers Containing Glucose Groups.

The stereocomplex of poly(lactic acid) containing glucose groups (sc-PLAG) was prepared by solution blending from equal amounts of poly(l-lactic acid) (PLLA) and poly(d-lactic acid-co-glucose) (PDLAG), which were synthesized from l- and d-lactic acid and glucose by melt polycondensation. The methods, including 1H nuclear magnetic resonance spectroscopy (1H NMR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), polarizing microscope (POM), scanning electron microscope (SEM), transmission electron microscope (TEM), and contact angle were used to determine the effects of the stereocomplexation of enantiomeric poly(lactic acid) (PLA) units, the amphiphilicity due to glucose residues and lactic acid units, and the interaction of glucose residues with lactic units on the crystallization performance, hydrophilicity, thermal stability, and morphology of samples. The results showed PDLAG was multi-armed, and partial OH groups of glucose residues in PDLAG might remain unreacted. The molecular weight (Mw), dispersity (Ɖ), and glucose proportion in the chain of PDLAG thereby had significant effects on sc-PLAG. There were the stereocomplexation of enantiomeric lactic units and the amphiphilic self-assembly of PDLAG in sc-PLAG, which resulted in glucose groups mainly in the surface phase and lactic units in the bulk phase. The sc-PLAG only possessed the stereocomplex crystal owing to the interaction between nearly equimolar of l-lactic units of PLLA and d-lactic units of PDLAG, and had no homo-crystallites of l- or d-lactic units, which improved the melting temperature (Tm) of sc-PLAG about 50 °C higher than that of PLLA. Glucose groups in sc-PLAG played an important role by forming heterogeneous nucleation, promoting amphiphilic self-assembly, and affecting the ordered arrangement of lactic units. The glass transition temperature (Tg), the melting temperature (Tm), crystallinity, crystallization rate, and water absorption of sc-PLAG showed similar changes with the increased glucose content in feeding. All these parameters increased at first, and the maximum appeared as glucose content in feeding about 2%, such as the maximum crystallinity of 48.8% and the maximum water absorption ratio being 11.7%. When glucose content in feeding continued increasing, all these performances showed a downward trend due to the decrease of arrangement regularity of lactic acid chains caused by glucose groups. Moreover, the contact angle of sc-PLAG decreased gradually with the increased glucose content in feeding to obtain the minimum 77.5° as the glucose content in feeding being 5%, while that of PLLA was 85.0°. The sc-PLAG possessed a regular microsphere structure, and its microspheres with a diameter of about 200 nm could be observed. In conclusion, sc-PLAG containing proper glucose amount could effectively enhance the crystallinity, hydrophilicity, and thermal stability of PLA material, which is useful for drug delivery, a scaffold for tissue engineering, and other applications of biomedicine.

Synthesis, DNA/BSA binding studies and in vitro biological assay of nickel(II) complexes incorporating tridentate aroylhydrazone and triphenylphosphine ligands.

Two new nickel (II) triphenylphosphine complexes derived from tridentate aroylhydrazone ligands [H2L1 = 2-hydroxy-3-methoxybenzylidene)benzohydrazone and H2L2 = N'-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone] and triphenylphosphine were prepared and their molecular structures were determined by single crystal X-ray diffraction analysis. Both nickel(II) complexes showed slightly distorted square planar geometry with one tridentate aroylhydrazone ligand coordinated through ONO donor atoms and one triphenylphosphine ligand coordinated to the nickel center through the phosphorus atom. DNA interaction studies indicated that both complexes possessed higher affinity to herring sperm DNA (HS-DNA) than the corresponding free aroylhydrazone ligand. Molecular docking investigations showed that both complexes could bind to DNA through intercalation of the phenyl rings between adjacent base pairs in the double helix. Meanwhile, bovine serum albumin (BSA) binding studies revealed the complexes could effectively interact with BSA and change the secondary structure of BSA. Further pharmacological evaluations of the synthesized complexes by in vitro antioxidant assays demonstrated high antioxidant activity against NO· and O2˙- radicals. The anticancer activity of each complex was assessed through in vitro cytotoxicity assays (CCK-8 kit) toward A549 and MCF-7 cancer cell and normal L-02 cell lines. Significantly, the Ni(II) complex derived from H2L1 ligand was found to be more effective cytotoxic toward MCF-7cancerous cell with the IC50 value equaled 9.7 µM, which showed potent cytotoxic activity over standard drug cisplatin. AbbreviationsA549human lung carcinoma cellBSAbovine serum albuminCCK-8Cell Counting Kit-8DFTdensity functional theoryDNAdeoxyribonucleic acidDPPH˙2,2-diphenyl-1-picrylhydrazylH2L12-hydroxy-3-methoxybenzylidene)benzohydrazone N'-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneH2L2N'-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneHOMOhighest occupied molecular orbitalIC50the 50% activityL-02human normal liver cellLOMOlowest unoccupied molecular orbital (LUMO)MCF-7human breast carcinoma cellNO˙nitric oxideO2˙-superoxide anionSODsuperoxide dismutaseCommunicated by Ramaswamy H. Sarma.

Magnetic separable chitosan microcapsules decorated with silver nanoparticles for catalytic reduction of 4-nitrophenol.

In the work, we have synthesized silver (Ag) nanoparticles deposited chitosan (CS) microcapsules with magnetic multiple Fe3O4 cores (denoted as Fe3O4/CS-Ag) as efficient catalysts for the reduction of 4-nitrophenol. The Fe3O4/CS-Ag catalysts are prepared by coating hydrophobic Fe3O4 nanoparticles with chitosan via a multiple emulsion-chemical crosslinking method and following in situ deposition of Ag nanoparticles onto the surfaces. The morphology and composition of the Fe3O4/CS-Ag microcapsules are characterized by Fourier transform infrared (FT-IR) spectra, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy. Moreover, the catalytic activity of the Fe3O4/CS-Ag catalyst was investigated, which shows a conversion efficiency as high as 98% within 15min for the reduction of p-nitrophenol to p-aminophenol. At the same time, the recovered Fe3O4/CS-Ag catalyst with an external magnet can retain good activity after 10 cycles. These results indicate that the multiple emulsion-chemical crosslinking method is an efficient and simple way for the preparation of magnetic separable chitosan microcapsules, and the fabricated Fe3O4/CS-Ag is a promising catalytic material with excellent catalytic activity and convenient recovery ability.

Synthesis and characterization of poly(lactic acid-co-glycolic acid) complex microspheres as drug carriers.

Poly(lactic-co-glycolic) acid (PLGA) is synthesized via melt polycondensation directly from lactic acid and glycolic acid with a feed molar ratio of 75/25. Bovine serum albumin, which is used as model protein, is entrapped into the poly(lactic-co-glycolic acid) microspheres with particle size of 260.9 ± 20.0 nm by the double emulsification method. Then it is the first report of producing more carboxyl groups by poly(lactic-co-glycolic acid) surface hydrolysis. The purpose is developing poly(lactic-co-glycolic acid) microspheres surface, which is modified with chitosan by chemical reaction between carboxyl groups and amine groups. The particle size and the positive zeta potential of the poly(lactic-co-glycolic acid)/chitosan microspheres are 388.2 ± 35.6 nm and 10.4 ± 2.9 mV, respectively. The drug loading ratio and encapsulation efficacy of poly(lactic-co-glycolic acid)/chitosan microspheres are 36.3% and 57.5%, which are higher than PLGA microspheres. Furthermore, the drug burst release of poly(lactic-co-glycolic acid)/chitosan microspheres at 10 h is decreased to 21.72% while the corresponding value of the poly(lactic-co-glycolic acid) microsphere is 64.56%. These results reveal that surface hydrolysis modification of poly(lactic-co-glycolic acid) is an efficient method to improve the negative potential and chemical reaction properties of the polymer. And furthermore, this study shows that chitosan-modified poly(lactic-co-glycolic acid) microspheres is a promising system for the controlled release of pharmaceutical proteins.

Effective method of chitosan-coated alginate nanoparticles for target drug delivery applications.

In the present study, alginate nanoparticles were firstly prepared for paclitaxel (PTX) delivery with an average size of 200 ± 21 nm. To improve the stability and targeting effect, the chitosan (CS) and folate-chitosan (FA-CS) were introduced to form PTX-loaded CS/ALG NPs and FA-CS/ALG NPs by a new double emulsion cross-linking electrostatic attraction method. The optimization chitosan concentration was 0.5% obtained from the experiment results. The CS/ALG-PTX NPs and FA-CS/ALG-PTX NPs had the average particle size of 306.9 ± 12.9 nm and 283.6 ± 19.2 nm with the zeta potential of 31.1 ± 1.3 mV and -2.98 ± 0.7 mV, and had higher drug loading and entrapment efficiencies than ALG-PTX NPs. The in vitro drug release profile along with release kinetics and mechanism from PTX-loaded NPs were studied under two simulated physiological conditions. Further, the in vitro anti-cancer activity of nanoparticles and the cellular uptake of nanoparticles on HepG2 cells were investigated. The results demonstrated that alginate, CS/ALG and FA-CS/ALG can be used as nanoformulation drug carriers by our new method, and FA-CS/ALG was a promising vehicle for anticancer drug targeted delivery system.

Facile synthesis of monodisperse of hollow mesoporous SiO2 nanoparticles and in-situ growth of Ag nanoparticles for antibacterial.

Monodispersed hollow mesoporous silica nanoparticles (HMSNs) are successfully synthesized via a facile dual template method, in which poly(styrene-co-methyl methacrylate-co-methacrylic acid) (PS-PMMA-PMAA) particles are used as hard template for producing the hollow structure and cetyltrimethylammonium bromide (CTAB) used for introducing the mesopores in the silica shells. The obtained HMSNs possess uniform diameter and morphology, and the shell of which could be adjusted by changing the addition of silicon precursor. The synthesized HMSNs have been characterized by transmission electron microscopy (TEM) and nitrogen physisorption. Furthermore, the HMSNs are used as support for in-situ deposition of silver nanoparticles (Ag NPs) using n-butylamine as reducing agent for AgNO3 in ethanol. Significantly, Ag NPs were successfully supported in the HMSNs without any aggregation. The Ag-deposited HMSNs showed excellent dispersibility in ethanol and water, and their antibacterial activity against Escherichia coli (E. coli) ATCC 25922 and Staphylococcus aureus (S. aureus) ATCC 6538 have been demonstrated. Therefore, the unique nanostructure based on the HMSNs provided a useful platform for the fabrication of antibacterial agent with superior activity and accessibility. And also, it is expected to be a significant template for the synthesis of other novel nanostructures.

A novel preparation method of paclitaxcel-loaded folate-modified chitosan microparticles and in vitro evaluation.

A new chitosan microparticles loading paclitaxel (PTX) for application as an oral delivery system were developed using a novel double emulsion crosslinking method. To improve the targeted effect, folic acid (FA) was introduced onto the surface of microparticles using chemical method. The method was based on Schiff reaction between amino group of chitosan and carboxyl group of FA, and folate-chitosan (FA-CS) conjugate was characterized using infrared spectrum analysis (FT-IR), and the microparticles were named as FA-CS-PTX/MPs. FA-CS-PTX/MPs had larger size of average diameter 223.6 nm, while PTX-loaded chitosan microparticles (CS-PTX/MPs) had 179.1 nm average diameter. The zeta potential of CS-PTX/MPs and FA-CS-PTX/MPs was 22.3 and 33.1 mV, respectively. SEM and TEM showed both the two microparticles had well-defined spherical structure. The in vitro drug release was studied under different pH conditions, and a two-phase kinetics model was found to be the most adequate kinetic model. Furthermore, the cytotoxicity activities of drug-carriers against L929 cells and the cellular uptake of PTX-loaded microparticles against HepG2 cells were investigated. Results demonstrated that FA-CS-PTX/MPs might be a promising drug carrier for promoting PTX cellular uptake and could be used as a potential tumor-targeted drug vector.