Synthesis of Block Copolymer Brush by RAFT and Click Chemistry and Its Self-Assembly as a Thin Film.

A well-defined block copolymer brush poly(glycidyl methacrylate)-graft-(poly(methyl methacrylate)-block- poly(oligo(ethylene glycol) methyl ether methacrylate)) (PGMA-g-(PMMA-b-POEGMA)) is synthesized via grafting from an approach based on a combination of click chemistry and reversible addition-fragmentation chain transfer (RAFT) polymerization. The resulting block copolymer brushes were characterized by 1H-NMR and size exclusion chromatography (SEC). The self-assembly of the block copolymer brush was then investigated under selective solvent conditions in three systems: THF/water, THF/CH3OH, and DMSO/CHCl3. PGMA-g-(PMMA-b-POEGMA) was found to self-assemble into spherical micelle structures as analyzed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The average size of the particles was much smaller in THF/CH3OH and DMSO/CHCl3 as compared with the THF/water system. Thin film of block copolymer brushes with tunable surface properties was then prepared by the spin-coating technique. The thickness of the thin film was confirmed by scanning electron microscopy (SEM). Atom force microscopy (AFM) analysis revealed a spherical morphology when the block copolymer brush was treated with poor solvents for the backbone and hydrophobic side chains. The contact angle measurements were used to confirm the surface rearrangements of the block copolymer brushes.

Bioresorbable hydrogels prepared by photo-initiated crosslinking of diacrylated PTMC-PEG-PTMC triblock copolymers as potential carrier of antitumor drugs.

PTMC-PEG-PTMC triblock copolymers were prepared by ring-opening polymerization of trimethylene carbonate (TMC) in the presence of dihydroxylated poly(ethylene glycol) (PEG) with Mn of 6000 and 10,000 as macro-initiator. The copolymers with different PTMC block Lengths and the two PEGs were end functionalized with acryloyl chloride. The resulting diacrylated PEG-PTMC-DA and PEG-DA were characterized by using NMR, GPC and DSC. The degree of substitution of end groups varied from 50.0 to 65.1%. Hydrogels were prepared by photo-crosslinking PEG-PTMC-DA and PEG-DA in aqueous solution using a water soluble photo-initiator under visible light irradiation. The effects of PTMC and PEG block lengths and degree of substitution on the swelling and weight loss of hydrogels were determined. Higher degree of substitution leads to higher crosslinking density, and thus to lower degree of swelling and weight loss. Similarly, higher PTMC block length also leads to lower degree of swelling and weight loss. Freeze dried hydrogels exhibit a highly porous structure with pore sizes from 20 to 100 µm. The biocompatibility of hydrogels was evaluated by MTT assay, hemolysis test, and dynamic clotting time measurements. Results show that the various hydrogels present outstanding cyto- and hemo-compatibility. Doxorubicin was taken as a model drug to evaluate the potential of PEG-PTMC-DA and PEG-DA hydrogels as drug carrier. An initial burst release was observed in all cases, followed by slower release up to more than 90%. The release rate is strongly dependent on the degree of swelling. The higher the degree of swelling, the faster the release rate. Finally, the effect of drug loaded hydrogels on SKBR-3 tumor cells was evaluated in comparison with free drug. Similar cyto-toxicity was obtained for drug loaded hydrogels and free drug at comparable drug concentrations. Therefore, injectable PEG-PTMC-DA hydrogels with outstanding biocompatibility and drug release properties could be most promising as bioresorbable carrier of hydrophilic drugs.

Biocompatibility and paclitaxel/cisplatin dual-loading of nanotubes prepared from poly(ethylene glycol)-polylactide-poly(ethylene glycol) triblock copolymers for combination cancer therapy.

Nanotubes were prepared by self-assembly of the copolymer using co-solvent evaporation method. The biocompatibility of the nanotubes was assessed in comparison with spherical micelles and filomicelles prepared from poly(ethylene glycol)-poly(L-lactide-co-glycolide) (PEG-PLGA) and poly(ethylene glycol)-poly(L-lactide) (PEG-PLA), respectively. Several aspects of biocompatibility of the aggregates were considered, including agar diffusion and MTT assay, release of cytokines, hemolysis, protein adsorption, dynamic clotting in vitro, and Zebrafish embryonic compatibility in vivo. The nanotubes present good cell compatibility and blood compatibility in vitro, and almost no toxicity towards Zebrafish embryos development in vivo. Furthermore, dual-loading of hydrophilic cisplatin and hydrophobic paclitaxel was achieved in the nanotubes with high loading content and loading efficiency. The release of both drugs was slower from dual-loaded nanotubes than from single-loaded ones, but the total amount of released drugs in higher for dual-loaded nanotubes than from single-loaded ones. Cellular uptake and inhibition tests showed that the nanotubes were successfully taken up by tumor cells and effectively inhibited cell growth. It is thus concluded that PEG-PLA-PEG nanotubes with outstanding biocompatibility could be promising for co-delivery of hydrophilic and hydrophobic agents in combination cancer therapy.

Self-assembled filomicelles prepared from polylactide-poly(ethylene glycol) diblock copolymers for sustained delivery of cycloprotoberberine derivatives.

Polylactide-poly(ethylene glycol) (PLA-PEG) block copolymers were synthesized by ring opening polymerization of l-lactide using a monomethoxy PEG (mPEG) as macroinitiator and zinc lactate as catalyst. The resulting diblock copolymers were characterized by 1H NMR and GPC. Polymeric micelles were prepared by self-assembly of copolymers in distilled water using co-solvent evaporation or membrane hydration methods. The resulting micelles are worm-like in shape as shown by TEM measurements. A hydrophobic anticancer drug, cycloprotoberberine derivative A35, was successfully loaded in PLA-PEG filomicelles with high encapsulation efficiency (above 88%). Berberine (BBR) was studied for comparison. In both methods, PLA-PEG filomicelles were prepared with a theoretical loading of 5%, 10% and 20%. Physical stability studies indicated that BBR/A35-loaded filomicelles were more stable when stored at 4 °C than at 25 °C. Compared with BBR-loaded filomicelles, A35-loaded filomicelles exhibited higher antitumor activity. Importantly, the in vitro cytotoxicity and stability of A35-loaded filomicelles evidenced the potential of drug-loaded filomicelles in the development of drug delivery systems.

Design and Development of Immunomodulatory Antigen Delivery Systems Based on Peptide/PEG-PLA Conjugate for Tuning Immunity.

Cancer vaccines are considered to be a promising tool for cancer immunotherapy. However, a well-designed cancer vaccine should combine a tumor-associated antigen (TAA) with the most effective immunomodulatory agents and/or delivery system to provoke intense immune responses against the TAA. In the present study, we introduced a new approach by conjugating the immunomodulatory molecule LD-indolicidin to the hydrophilic chain end of the polymeric emulsifier poly(ethylene glycol)-polylactide (PEG-PLA), allowing the molecule to be located close to the surface of the resulting emulsion. A peptide/polymer conjugate, named LD-indolicidin-PEG-PLA, was synthesized by conjugation of the amine end-group of LD-indolicidin to the N-hydroxysuccinimide-activated carboxyl end-group of PEG. As an adjuvant for cancer immunotherapeutic use, TAA vaccine candidate formulated with the LD-indolicidin-PEG-PLA-stabilized squalene-in-water emulsion could effectively help to elicit a T helper (Th)1-dominant antigen-specific immune response as well as antitumor ability, using ovalbumin (OVA) protein/EG7 cells as a TAA/tumor cell model. Taken together, these results open up a new approach to the development of immunomodulatory antigen delivery systems for vaccine adjuvants and cancer immunotherapy technologies.

In vivo degradation of copolymers prepared from L-lactide, 1,3-trimethylene carbonate and glycolide as coronary stent materials.

A series of high molecular weight polymers were prepared by ring opening polymerization of L-lactide (L-LA), 1,3-trimethylene carbonate (TMC) and glycolide using stannous octoate as catalyst. The resulting polymers were characterized by gel permeation chromatography, (1)H nuclear magnetic resonance, differential scanning calorimeter and tensile tests. All the polymers present high molecular weights. Compared with PLLA and PTLA copolymers, the terpolymers exhibit interesting properties such as improved toughness and lowered crystallinity with only slightly reduced mechanical strength. In vivo degradation was performed by subcutaneous implantation in rats to evaluate the potential of the copolymers as bioresorbable coronary stent material. The results show that all the polymers conserved to a large extent their mechanical properties during the first 90 days, except the strain at break which exhibited a strong decrease. Meanwhile, significant molecular weight decrease and weight loss are detected in the case of terpolymers. Therefore, the PTLGA terpolymers present a good potential for the development of totally bioresorbable coronary stents.

Polysaccharides as a Hydrophilic Building Block of Amphiphilic Block Copolymers for the Conception of Nanocarriers.

Polysaccharides are gaining increasing attention for their relevance in the production of sustainable materials. In the domain of biomaterials, polysaccharides play an important role as hydrophilic components in the design of amphiphilic block copolymers for the development of drug delivery systems, in particular nanocarriers due to their outstanding biocompatibility, biodegradability, and structural versatility. The presence of a reducing end in polysaccharide chains allows for the synthesis of polysaccharide-based block copolymers. Compared with polysaccharide-based graft copolymers, the structure of block copolymers can be more precisely controlled. In this review, the synthesis methods of polysaccharide-based amphiphilic block copolymers are discussed in detail, taking into consideration the structural characteristics of polysaccharides. Various synthetic approaches, including reductive amination, oxime ligation, and other chain-end modification reactions, are explored. This review also focuses on the advantages of polysaccharides as hydrophilic blocks in polymeric nanocarriers. The structure and unique properties of different polysaccharides such as cellulose, hyaluronic acid, chitosan, alginate, and dextran are described along with examples of their applications as hydrophilic segments in the synthesis of amphiphilic copolymers to construct nanocarriers for sustained drug delivery.

Chitosan-based GOx@Co-MOF composite hydrogel: A promising strategy for enhanced antibacterial and wound healing effects.

A novel composite hydrogel was synthesized via Schiff base reaction between chitosan and di-functional poly(ethylene glycol) (DF-PEG), incorporating glucose oxidase (GOx) and cobalt metal-organic frameworks (Co-MOF). The resulting CS/PEG/GOx@Co-MOF composite hydrogel was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and energy-dispersive X-ray spectroscopy (EDS). The results confirmed successful integration and uniform distribution of Co-MOF within the hydrogel matrix. Functionally, the hydrogel exploits the catalytic decomposition of glucose by GOx to generate gluconic acid and hydrogen peroxide (H2O2), while Co-MOF gradually releases metal ions and protects GOx. This synergy enhanced the antibacterial activity of the composite hydrogel against both Gram-positive (S. aureus) and Gram-negative bacteria (E. coli), outperforming conventional chitosan-based hydrogels. The potential of the composite hydrogel in treating wound infections was evaluated through antibacterial and wound healing experiments. Overall, CS/PEG/GOx@Co-MOF hydrogel holds great promise for the treatment of wound infections, paving the way for further research and potential clinical applications.

Graphene quantum dot-mediated anchoring of highly dispersed bismuth nanoparticles on porous graphene for enhanced electrocatalytic CO2 reduction to formate.

The electrocatalytic reduction of CO2 to produce formic acid is gaining prominence as a critical technology in the pursuit of carbon neutrality. Nonetheless, it remains challenging to attain both substantial formic acid production and high stability across a wide voltage range, particularly when utilizing bismuth-based catalysts. Herein, we present a novel graphene quantum dot-mediated synthetic strategy to achieve the uniform deposition of highly dispersed bismuth nanoparticles on porous graphene. This innovative design achieves an elevated faradaic efficiency for formate of 87.0% at -1.11 V vs. RHE with high current density and long-term stability. When employing a flow cell, a maximum FEformate of 80.0% was attained with a total current density of 156.5 mA cm-2. The exceptional catalytic properties can be primarily attributed to the use of porous graphene as the support and the auxiliary contribution of graphene quantum dots, which enhance the dispersion of bismuth nanoparticles. This improved dispersion, in turn, has a significantly positive impact on CO2 activation and the generation of *HCOO intermediates to facilitate the formation of formate. This work presents a straightforward technique to create uniform metal nanoparticles on carbon materials for advancing various electrolytic applications.

Genetic manipulation in Sulfolobus islandicus and functional analysis of DNA repair genes.

Recently, a novel gene-deletion method was developed for the crenarchaeal model Sulfolobus islandicus, which is a suitable tool for addressing gene essentiality in depth. Using this technique, we have investigated functions of putative DNA repair genes by constructing deletion mutants and studying their phenotype. We found that this archaeon may not encode a eukarya-type of NER (nucleotide excision repair) pathway because depleting each of the eukaryal NER homologues XPD, XPB and XPF did not impair the DNA repair capacity in their mutants. However, among seven homologous recombination proteins, including RadA, Hel308/Hjm, Rad50, Mre11, HerA, NurA and Hjc, only the Hjc nuclease is dispensable for cell viability. Sulfolobus encodes redundant BER (base excision repair) enzymes such as two uracil DNA glycosylases and two putative apurinic/apyrimidinic lyases, but inactivation of one of the redundant enzymes already impaired cell growth, highlighting their important roles in archaeal DNA repair. Systematically characterizing these mutants and generating mutants lacking two or more DNA repair genes will yield further insights into the genetic mechanisms of DNA repair in this model organism.

In situ Hydrogels Prepared by Photo-initiated Crosslinking of Acrylated Polymers for Local Delivery of Antitumor Drugs.

A triblock copolymer was synthesized by ring opening polymerization of ε-caprolactone in the presence of poly(ethylene glycol) (PEG). The resulted PCL-PEG-PCL triblock copolymer, PEG and monomethoxy (MPEG) were functionalized by end group acrylation. NMR and FT-IR analyses evidenced the successful synthesis and functionalization of polymers. A series of photo-crosslinked hydrogels composed of acrylated PEG-PCL-Acr and MPEG-Acr or PEG-Acr were prepared by exposure to visible light using lithium phenyl-2,4,6-trimethylbenzoylphosphinate as initiator. The hydrogels present a porous and interconnected structure as shown by SEM. The swelling performance of hydrogels is closely related to the crosslinking density and hydrophilic content. Addition of MPEG or PEG results in increase in water absorption capacity of hydrogels. In vitro degradation of hydrogels was realized in the presence of a lipase from porcine pancreas. Various degradation rates were obtained which mainly depend on the hydrogel composition. MTT assay confirmed the good biocompatibility of hydrogels. Importantly, in situ gelation was achieved by irradiation of a precursor solution injected in the abdomen of mice. Doxorubicin (DOX) was selected as a model antitumor drug to evaluate the potential of hydrogels in cancer therapy. Drug-loaded hydrogels were prepared by in situ encapsulation. In vitro drug release studies showed a sustained release during 28 days with small burst release. DOX-loaded hydrogels exhibit antitumor activity against A529 lung cancer cells comparable to free drug, suggesting that injectable in situ hydrogel with tunable properties could be most promising for local drug delivery in cancer therapy.

Correlations between rheological and mechanical properties of fructo-polysaccharides extracted from Ornithogalum billardieri as biobased adhesive for biomedical applications.

Polysaccharides are extracted from Ornithogalum by maceration using different ultrasound (US) treatment times (0%US, 50%US, 100%US), and under optimized extraction conditions (OP%US). The total carbohydrates content (TCC) and proteins content of the extracts were determined. Data show that the extraction parameters significantly influence the extracts composition. Rheological measurements allowed determining the liquid, intermediate and gel states of the extract's solutions. The adhesion strength of the solutions was evaluated on paper and polylactide (PLA) substrates to evaluate their potential as environmentally friendly adhesive. OP%US presents the highest adhesion strength (1418.3 kPa) on paper, and is further tested on pork skin substrates. The adhesion strength is higher on skin/paper (870 kPa) than on skin/skin (411 kPa) substrate due to the capillary force of paper which allows penetration of adhesive into the micropores of paper. The correlation between rheological properties and adhesion strength indicates that the adhesion strength strongly depends on the state of adhesives and the substrate type. SEM analyses show that higher adhesion strength (intermediate and gel states) involves both cohesive and adhesive failure, whereas only adhesive failure is observed in liquid state on PLA substrates. Therefore, these polysaccharides extracts could be very promising as tissue adhesive in medical applications.

Novel chitosan based metal-organic polyhedrons/enzyme hybrid hydrogel with antibacterial activity to promote wound healing.

This work aimed to develop a novel chitosan based metal-organic polyhedrons (MOPs)/enzyme hybrid hydrogel with superior antimicrobial properties in wound healing treatment. Hybrid hydrogel was prepared by crosslinking glucose oxidase (GOx), vanadium metal-organic polyhedrons (VMOP-2) and chitosan using glutaraldehyde as crosslinker. The formed GVCS hydrogel was characterized by using various techniques, including FTIR, SEM, XPS, TGA and EDX. Data show that GVCS hydrogel was successfully obtained with uniform distribution of GOx and VMOP-2 in the hydrogel structure. Antibacterial tests show that GVCS hydrogel exhibits better bactericidal effect on both gram-negative bacteria (S. aureus) and gram-positive bacteria (E. coli) compared to other hydrogel samples because of its hydroxyl radicals generation capacity in the presence of glucose. MTT assay shows that the hydrogel presents good cell compatibility. In vivo experiments using an infected wound model indicate that GVCS hydrogel can effectively facilitate wound healing. Therefore, chitosan based MOPs/enzyme hybrid hydrogel could be most promising for antibacterial therapy in clinical applications.

Effect of glucose substitution by low-molecular weight chitosan-derivatives on functional, structural and antioxidant properties of maillard reaction-crosslinked chitosan-based films.

In this study, the effects of different temperatures, incubation times and types of reducing sugars, including glucose and different low molecular weight (Mw) chito-oligosaccharides (COS) with varying acetylation degree (AD), on the extent of Maillard reaction (MR) on chitosan-based films were studied. Interestingly, an improvement of structural and functional properties of all MR-crosslinked films was noted, which is more pronounced by heating at higher temperature and exposure time. These findings were proved through Fourier-transform infrared and X-ray diffraction analyses. In addition, color change and Ultraviolet spectra demonstrate that glucose addition provides the high extent of MR, followed by COS1 (Mw < 4.4 kDa; AD, 18.20%) and COS2 (Mw < 4.4 kDa; AD, 10.63%). These results were confirmed by enhanced water resistance and thermal properties. Moreover, MR-chitosan/COS films showed the highest mechanical properties, whereas, glucose-loaded films were brittle, as demonstrated by scanning electron microscopy micrographs. Furthermore, MR-chitosan/COS1 films exhibited the better antioxidant behavior followed by chitosan/glucose and chitosan/COS2 films, mainly at higher heating-conditions. Thereby, MR-crosslinked chitosan/COS based films were attractive to be applied as functional and active coating-materials in various fields.

Anisotropic self-assembling micelles prepared by the direct dissolution of PLA/PEG block copolymers with a high PEG fraction.

A series of polylactide-poly(ethylene glycol) (PLA-PEG) block copolymers with a high PEG fraction were synthesized by the ring-opening polymerization of L- or D-lactide in the presence of mono- or dihydroxyl PEG using nontoxic zinc lactate as a catalyst. Micelles were then prepared by direct dissolution of the obtained water-soluble copolymers in an aqueous medium without heating or using any organic solvents. Large anisotropic micelles instead of conventional spherical ones were observed from a transmission electron microscopy examination. Various parameters influencing the structure of the novel micelles were considered, such as the copolymer chain structure, molar mass, PEG fraction, copolymer concentration, and stereocomplexation between L- and D-PLA blocks. Anisotropic micelles were obtained for both diblock and triblock copolymers but vanished with increasing molar mass of the copolymers. The morphology of micelles strongly depends on the PEG fraction. Anisotropic micelles were found only in an intermediate EO/LA ratio range in which a higher PEG fraction leads to a higher length/width ratio of micelles. Stereocomplexation between L- and D-PLA or a lower concentration disfavors the formation of anisotropic micelles. Under appropriate concentrations, spherical and anisotropic micelles coexist in the same micellar solution. Moreover, it was found that anisotropic micelles are susceptible to further self-assemble into more organized complex aggregates. Similar results were obtained from light scattering and aqueous gel permeation chromatography measurements. A novel model is proposed to explain the formation of anisotropic micelles and the effects of various parameters on the structure of micelles in an aqueous medium.

In vivo study on the histocompatibility and degradation behavior of biodegradable poly(trimethylene carbonate-co-D,L-lactide).

The aim of this study was to explore the in vivo behavior and histocompatibility of poly(trimethylene carbonate-co-D,L-lactide) (PDLLA/TMC) and its feasibility of manufacturing cardiovascular stents. Copolymers with 50/50 molar ratio were synthesized by ring-opening polymerization with TMC and D, L-LA, or TMC and L-LA. Poly(L-lactide) (PLLA) was synthesized as a control. The films of the three polymers were implanted into 144 Wistar rats. At different time points of implantation, polymer films were explanted for the evaluation of degradation characteristics and histocompatibility using size exclusion chromatography , nuclear magnetic resonance , environmental scanning electron microscope , and optical microscope. Results showed that there were differences in the percentage of mass loss, molecular weight, shape and appearance changes, and inflammation cell counts between different polymers. With the time extended, the film's superficial structure transformed variously, which was rather obvious in the polymer of PDLLA/TMC. In addition, there were relatively lower inflammation cell counts in the PDLLA/TMC and poly(trimethylene carbonate-co-L-lactide) (PLLA/TMC) groups at different time points in comparison with those in the PLLA group. The differences were of statistical significance (P< 0.05) in the group of PDLLA/TMC vs. PLLA, and the group of PLLA/TMC vs. PLLA, but not within the PDLLA/TMC and PLLA/TMC groups (P> 0.05). These results suggested that the polymer of PDLLA/TMC (50/50) with favorable degradation performance and histocompatibility is fully biodegradable and suitable for manufacturing implanted cardiovascular stents.

Evaluation of a novel paclitaxel-eluting stent with a bioabsorbable polymeric surface coating in the porcine artery injury model.

PURPOSE: Drug-eluting stents (DES) are unique in allowing sustained release after a single short intervention. The challenge with DES still remaining is the optimal combination of a biocompatible drug-eluting matrix including an antiproliferative drug. We studied the role of a novel paclitaxel-eluting stent with a bioabsorbable polymer coating in preventing vascular restenosis in the porcine artery injury model. MATERIAL AND METHODS: Bare metal stents (BMS); polymer-coated-only stents (POLY); and polymer-based paclitaxel-eluting stents (PACL) were randomly implanted in pig femoral arteries. The dose density of paclitaxel was 1 microg/mm2 with in vitro studies demonstrating a gradual elution over a course of 6 month. RESULTS: After 1-, 3- and 6-month follow-up, respectively, the animals underwent angiographic restudy and were terminated for histomorphometrical and histopathological analyses. At 1 month, the PACL group had the lowest histological percent stenosis when compared to the BMS and POLY groups (20 +/- 4% vs 39 +/- 6% and 41 +/- 6%, respectively, P < 0.05). At 3 months, the PACL group still presents the lowest level of histological percent stenosis among the three groups (27 +/- 6% vs 50 +/- 10% and 46 +/- 5%, respectively, P < 0.01). Six months later, the PACL group showed a similar histological percent stenosis as the BMS and POLY groups (44 +/- 9% vs 56 +/- 11% and 53 +/- 9%, respectively, P = 0.145). CONCLUSIONS: This study shows favourable vascular compatibility and efficacy for a novel DES to inhibit in-stent neointima formation and preserve lumen area in the porcine artery model.

Cedrol alleviates the apoptosis and inflammatory response of IL-1ß-treated chondrocytes by promoting miR-542-5p expression.

Cedrol has been shown to exert anti-tumor, anti-inflammatory, and anti-oxidative effects, but its role in osteoarthritis (OA) is unclear. This study aimed to explore the effect of cedrol in OA. Chondrocytes were isolated from newborn rats and cultured in Dulbecco's modified Eagle's medium (DMEM). Then, Alcian blue staining was used to identify the chondrocytes. IL-1ß and cedrol were used to treat chondrocytes. Cell viability and apoptosis were measured by MTT and flow cytometry assays, respectively. The expressions of miR-542-5p, miR-26b-5p, miR-572, miR-138-5p, miR-328-3p, miR-1254, Bcl-2, Bax, iNOS, COX-2, and MMP-13 were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot. NO and PGE2 levels were detected by ELISA. All the cells extracted from the newborn rats were dyed blue, indicating that the cells were chondrocytes. IL-1ß could reduce the viability and promote apoptosis and inflammatory response of chondrocytes, while cedrol could reverse the effect of IL-1ß. In addition, cedrol could significantly increase the expression of miR-542-5p in IL-1ß-treated chondrocytes. Moreover, miR-542-5p inhibitor could partly reverse the effect of cedrol in the apoptosis and inflammation response of chondrocytes. Cedrol alleviated IL-1ß-induced apoptosis and inflammatory response of chondrocytes by promoting miR-542-5p expression.

Development of delivery system based on marine chitosan: Encapsulationand release kinetic study of antioxidant peptides from chitosan microparticle.

The present work aims to encapsulate goby fish protein hydrolysate (GPH), endowed with antioxidant activity, through ionic gelation process using blue crab chitosan (CH) and tripolyphosphate anions and to evaluate the structural, thermal and antioxidant properties of the elaborated microparticles (MPs). The GPH-loaded MPs present spherical shape as seen by scanning electron microscopy (SEM) images and positive zeta potential. The increase of loaded GPH concentration led to the increase of encapsulation efficiency (EE) and to the reduction of the particle size. In fact, MPs, loaded with 2 and 5 mg/ml GPH, had EE values of 44 and 58% and mean particles size of 4.81 and 3.78 µm, respectively. Furthermore, thermogravimetric analysis (TGA) profiles revealed the enhanced thermal stability of encapsulated biopeptides compared to the free ones. Release kinetic data showed a Fickian diffusion behavior which follows swelling and a diffusion-controlled mechanism for peptides liberation. Finally, as opposed to unloaded MPs, an improvement of the antioxidant activity of the loaded MPs with biopeptides was observed.

Biobased dynamic hydrogels by reversible imine bonding for controlled release of thymopentin.

Thymopentin (TP5) is widely used in the treatment of autoimmune diseases, but the short in vivo half-life of TP5 strongly restricts its clinical applications. A series of blank and TP5 loaded hydrogels were synthesized via reversible dual imine bonding by mixing water soluble O-carboxymethyl chitosan (CMCS) with a dynamer (Dy) prepared from Jeffamine and benzene-1,3,5-tricarbaldehyde. TP5 release from hydrogels was studied at 37 °C under in vitro conditions. The molar mass of CMCS, drug loading conditions and drug content were varied to elucidate their effects on hydrogel properties and drug release behaviors. Density functional theory was applied to theoretically confirm the chemical connections between TP5 or CMCS with Dy. All hydrogels exhibited interpenetrating porous architecture with average pore size from 59 to 83 µm, and pH-sensitive swelling up to 10,000% at pH 8. TP5 encapsulation affected the rheological properties of hydrogels as TP5 was partially attached to the network via imine bonding. Higher TP5 loading led to higher release rates. Faster release was observed at pH 5.5 than at pH 7.4 due to lower stability of imine bonds in acidic media. Fitting of release data using Higuchi model showed that initial TP5 release was essentially diffusion controlled. All these findings proved that the dynamic hydrogels are promising carriers for controlled delivery of hydrophilic drugs, and shed new light on the design of drug release systems by both physical mixing and reversible covalent bonding.