Conventional antibiotic treatment is in most cases insufficient to eradicate biofilm-related infections, resulting in high risk of treatment failure and recurrent infections. Recent studies have ...shown that novel methods of antibiotic delivery can improve clinical outcomes and reduce the emergence of antibiotic resistance. The objectives of this work were to develop and evaluate a targeting nanocarrier system that enables effective delivery of antimicrobial drugs to Staphylococcus aureus, a commonly virulent human pathogen. For this purpose, we first prepared a formulation of polymeric nanoparticles (NPs) suitable for encapsulation and sustained release of antibiotics. A specific antibody against S. aureus was used as a targeting ligand and was covalently immobilized onto the surface of nanoparticulate materials. It was demonstrated that the targeting NPs preferentially bound S. aureus cells and presented an elevated accumulation in the S. aureus biofilm. Compared to free-form antibiotic, the antibiotic-loaded targeting NPs significantly enhanced in vitro bactericidal activity against S. aureus both in planktonic and biofilm forms. Using a mouse infection model, we observed improved therapeutic efficacy of these antibiotic-loaded NPs after a single intravenous administration. Taken together, our studies show that the targeting nanoparticulate system could be a promising strategy to enhance the biodistribution of antibiotics and thereby improve their efficacy.
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•Ferulic acid (FA) was grafted on pullulan (PUL) using N,N’-carbonyldiimidazole.•An associative behaviour was observed in dilute solution.•The antioxidant properties provided by FA ...are preserved.•Action of laccase resulted in the formation of a cytocompatible hydrogel.•The initial PUL concentration and the amount of grafted FA controlled the properties.
A novel eco-friendly two-step synthesis process of neutral pullulan (PUL)-ferulic acid (FA) conjugates was reported in this work. Ferulic acid was first transformed to activated ferulate-imidazolide using N,N’-carbonyldiimidazole (CDI), a green activated reagent. Issued product was then reacted with pullulan. PUL-FA derivatives were characterized by FTIR and 1H NMR leading to substitution degrees (DS) between 0.02 and 0.1 (mol FA per mol PUL repeat unit). The study in dilute regime indicated an associative behavior with the presence of aggregate structures in solution due to the hydrophobic interactions between the grafted FA onto polysaccharide backbones. Laccase from Trametes versicolor was then used to crosslink polysaccharide chains to obtain biomimetic PUL-FA hydrogels. Gelling’s kinetics were analyzed with rheology in dynamic mode showing the impact of laccase amount, DS and concentration. Mechanical and swelling properties appear related only to DS and concentration of PUL-FA products.
Hyaluronic acid (HA) is a naturally occurring polysaccharide which has been extensively exploited in biomedical fields owing to its outstanding biocompatibility. Self‐assembly of HA and polycations ...through electrostatic interactions can generate colloidal polyelectrolyte complexes (PECs), which can offer a wide range of applications while being relatively simple to prepare with rapid and “green” processes. The advantages of colloidal HA‐based PECs stem from the combined benefits of nanomedicine, green chemistry, and the inherent properties of HA, namely high biocompatibility, biodegradability, and biological targeting capability. Accordingly, colloidal PECs from HA have received increasing attention in the recent years as high‐performance materials for biomedical applications. Considering their potential, this review is aimed to provide a comprehensive understanding of colloidal PECs from HA in complex with polycations, from the most fundamental aspects of the preparation process to their various biomedical applications, notably as nanocarriers for delivering small molecule drugs, nucleic acids, peptides, proteins, and bioimaging agents or the construction of multifunctional platforms.
Hyaluronic acid (HA) is a very promising polysaccharide for biomedical applications. This review provides a comprehensive overview of the development of nanoparticulate systems by HA‐based polyelectrolyte complexation. The main achievements and applications for the delivery of active substances or the construction of multifunctional platforms are discussed.
Hyaluronic acid (HA) of different molar masses from 38 000 to 990 000 g mol−1 were used as terminating agents during the cationic ring-opening polymerisation of 2-methyl-2-oxazoline. HA was first ...converted into a tetrabutylammonium salt to solubilize it in polar aprotic organic solvents where the termination was conducted by varying the excess of HA units to the growing poly(2-methyl-2-oxazoline) (PMeOx) chains (with various PMeOx degree of polymerisation). This led to HA derivatives with various PMeOx degrees of substitution from 4% up to 13% (determined by 1H NMR). HA-g-PMeOx copolymers were analysed by Size Exclusion Chromatography with on-line detectors (Multi-angle light scattering, Viscometer, Refractive index) in 0.1 mol L−1 LiNO3 to study their macromolecular characteristics in dilute medium. The reaction was applied to functionalize HA with thermo-responsive poly(2-isopropyl-2-oxazoline)-co-poly(2-n-butyl-2-oxazoline) moieties, resulting in materials displaying thermally dependent hydrogel properties in aqueous solutions which could be used for biomedical applications.
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•Poly(2-methyl-2-oxazoline) was grafted on hyaluronic acid by a one-pot approach•The reaction was done on hyaluronic acid of different molar masses•Grafting degrees from 5% to 13% were achieved with polyoxazolines of various DPn•Modified hyaluronic acid presented a random coil conformation in water•The reaction was used to design thermo-responsive hyaluronic acid based hydrogels
Antimicrobial resistance is one of the greatest threats to global health. Although the efforts in antibiotic drug discovery continue to play a pivotal role, this solution alone probably will not be ...enough to ensure the required level of infection control in the future. New strategies and innovative modes of action are desperately needed to preserve the effectiveness of antimicrobials. Accordingly, antibiotic delivery based on polymeric nanoparticles is one of the possible methods that has been recently explored to improve their pharmacokinetic profile. Through optimized access of antibiotics to their sites of action, nanocarriers can unlock the full potential of the antibiotic cargoes, extend the antimicrobial spectrum, and reduce the required dose of antibiotic while preserving efficacy. Additionally, the use of an antibiotic-loaded nanocarrier is also considered a steady solution as novel molecules can be continuously developed and incorporated into the delivery platform. This review describes the present state of polymeric nanocarriers in enhancing antibiotic treatment, including improved pharmacokinetic properties and restored antibiotic efficacy against drug-resistant bacteria. Additionally, the current challenges and the future direction of this field are discussed.
•Ultrasonic extraction of CEP were carried for the first time.•BBD was applied to optimize the extraction conditions for CEP.•Highest CEP yield agrees closely with the predicted yield.•CEP are a low ...methoxyl pectic polysaccharides.•CEP showed strong antioxidant and antiglycation activities at 10mg/mL.
In this study, Box-Behnken design was used to optimize the ultrasonic extraction of Carpobrotus edulis polysaccharides (CEP), and the effect of time, extraction temperature and water to material ratio was evaluated. Optimum conditions were 1.77h, 78.0°C and 33.04mL/g to improved CEP yield (7.84%), which is in good agreement with the predicted yield 7.77%. Then, the physico-chemical, antioxidant and antiglycation properties of optimized CEP were studied, and the total sugar and galacturonic acid content were 89.7 and 63.2%, respectively. The composition of neutral monosaccharide was arabinose, xylose, rhamnose and mannose in the molar percentage of 71.84, 14.80, 8.57, and 4.79%, respectively. In addition, (1H, and 13C) NMR and FTIR analyses confirmed the presence of uronic acids in the free and methyl ester forms with a degree of esterification of 31.27%. Therefore, this finding showed that CEP is a low methoxyl pectic polysaccharide, with an average molecular weight about 65,000g/mol. Finally, the results indicated that CEP presents strong antioxidant activities in vitro (DPPH, chelating ability and reducing power), and significantly inhibits lipid peroxidation and the formation of fluorescent advanced glycation end products in glucose-BSA system model.
Polysaccharides from marine algae are one novel source of plant defense elicitors for alternative and eco-friendly plant protection against phytopathogens. The effect of exopolysaccharides (EPS) ...produced by
on elicitation of
defense responses against
was evaluated. Firstly, in order to enhance EPS production, a Box-Behnken experimental design was carried out to optimize NaCl, NaNO
and MgSO
concentrations in the culture medium of microalgae. A maximum EPS production (2.45 g/L) higher than that of the control (0.7 g/L) was observed for 41.62 g/L NaCl, 0.63 g/L NaNO
and 7.2 g/L MgSO
concentrations. Structurally, the EPS contained mainly galactose, xylose and glucose. Secondly, the elicitor effect of EPS was evaluated by investigating the plant defense-related signaling pathways that include activation of Salicylic or Jasmonic Acid-dependent pathway genes. A solution of 2 mg/mL of EPS has led to the control of fungal growth by the plant. Results showed that EPS foliar application induced phenylalaline ammonia lyase and H
O
accumulation. Expression profile analysis of the defense-related genes using qRT-PCR revealed the up-regulation of Superoxide dismutases (SOD), Peroxidase (POD), Pathogenesis-related protein 1 (PR-1) and Cytochrome P450 monooxyge-nase (CYP), while Catalase (CAT) and Plant defensin 1.2 (PDF1.2) were not induced. Results suggest that EPS may induce the elicitation of
.
's defense response against
, activating the Salicylic Acid pathway.
•Two water-soluble polysaccharides were extracted from the Tunisian brown alga C. compressa.•The sulfated fucoidan was a galactofucan with a backbone of α-(1,3) and α-(1,4)-l-Fucp, highly ...substituted.•The sodium alginate showed a M/G ratio closed to 0.77 and the ability to form solid and rigid gel.•The polysaccharides displayed antioxidant activities with IC50 values under 560 μg/mL.
A fucoidan (CCF) and a sodium alginate (CCSA) were extracted and purified from the Tunisian brown seaweed Cystoseira compressa. CCF was a highly sulfated heterogalactofucan composed of α-(1→3), α-(1→4)-linked l-Fucp as main backbone which could be highly branched (31.84%) at O-3 and O-4 positions of α-(1→4)-l-Fucp and α-(1→3)-l-Fucp by terminal monosaccharides and side chains such as terminal α-l-Fucp, terminal β-d-Galp, β-d-Galp-(1→3)-α-l-Fucp and β-d-Galp-(1→4)-α-l-Fucp. The ratio of α-(1→3)/α-(1→4) linkages was estimated at 3.86:1. CCSA was characterized by HPAEC-PAD, GC/MS-EI, ATR-FTIR, and 1H-NMR. The M/G ratio was M/G = 0.77, indicating that CCSA respectively contained 44% and 56% of mannuronic and guluronic acids. The values of FGG, FMM, FGM (or FMG) blocks as well as the parameter η were estimated. The two polysaccharides exhibited effective antioxidant activities by ferrous ion chelation, ferric ion reduction and DPPH radical-scavenging, outlining their potentials as natural additives.
•Asafetida gum was successfully extracted from oleo-gum-resin of Ferula assa foetida.•The gum had arabinogalactan structure containing Galp, Araf, Arap, Rhap and GlcA.•The core residue contained ...β-(1→3)-Galp with 3,6-, 3,4- and 3,4,6- linkages.•Protein residue was linked to polysaccharide perhaps at β-D-Galp site.
The gum asafoetida, an oleo-gum-resin from root of Ferula assa foetida, was extracted through alcoholic procedure followed by water extraction and then biochemically characterized using colorimetric assays, Fourier infrared spectroscopy, gas chromatography coupled to mass spectrometry, and 1D and 2D nuclear magnetic resonance. The gum was mainly composed of carbohydrates (67.39% w/w) with a monosaccharide distribution of 11.5: 5.9: 2.3: 1 between Gal, Ara, Rha and GlcA (molar ratio) and proteins (arabinogalactan protein). The polysaccharide consisted of a (1→3)-β-d-galactan backbone ramified predominantly from O-6 but also from O-4 and O-4,6. Side chains included terminal-α-l-Araf, terminal-α-l-Rhap, (1→3)-α-l-Araf, (1→5)-α-l-Araf, terminal-β-d-Galp, β-d-GlcA and traces of (1→4)-β-d-GlcA. X-ray diffraction pattern showed a semi crystalline microstructure. Thermal behavior of the gum was evaluated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) revealed temperatures below and upper 200°C as dominant regions of weight loss.
Reaction between methyl α-
d-glucopyranoside and sodium trimetaphosphate (STMP) in alkaline medium was studied by nuclear magnetic resonance spectroscopy (
31P,
1H,
13C). We have determined the ...various formed species and the reaction mechanism.
An NMR spectroscopy study (
31P,
1H,
13C) of the postulated crosslinking mechanism of sodium trimetaphosphate (STMP) on polysaccharides is reported using methyl α-
d-glucopyranoside as a model. In a first step, reaction of STMP with Glc-OMe gives grafted sodium tripolyphosphate (STPP
g). On the one hand, STTP
g can react with a second alcohol functionality to give a crosslinked monophosphate. On the other hand, a monophosphate (grafted phosphate) could be obtained by alkaline degradation of STPP
g. NMR spectroscopy allows to detect the various species formed and to obtain the crosslinking density of STMP–polysaccharides hydrogels.
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