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1.
Mar Drugs ; 21(5)2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37233489

RESUMO

Oligosaccharides derived from λ-carrageenan (λ-COs) are gaining interest in the cancer field. They have been recently reported to regulate heparanase (HPSE) activity, a protumor enzyme involved in cancer cell migration and invasion, making them very promising molecules for new therapeutic applications. However, one of the specific features of commercial λ-carrageenan (λ-CAR) is that they are heterogeneous mixtures of different CAR families, and are named according to the thickening-purpose final-product viscosity which does not reflect the real composition. Consequently, this can limit their use in a clinical applications. To address this issue, six commercial λ-CARs were compared and differences in their physiochemical properties were analyzed and shown. Then, a H2O2-assisted depolymerization was applied to each commercial source, and number- and weight-averaged molar masses (Mn and Mw) and sulfation degree (DS) of the λ-COs produced over time were determined. By adjusting the depolymerization time for each product, almost comparable λ-CO formulations could be obtained in terms of molar masses and DS, which ranged within previously reported values suitable for antitumor properties. However, when the anti-HPSE activity of these new λ-COs was screened, small changes that could not be attributed only to their small length or DS changes between them were found, suggesting a role of other features, such as differences in the initial mixture composition. Further structural MS and NMR analysis revealed qualitative and semi-quantitative differences between the molecular species, especially in the proportion of the anti-HPSE λ-type, other CARs types and adjuvants, and it also showed that H2O2-based hydrolysis induced sugar degradation. Finally, when the effects of λ-COs were assessed in an in vitro migration cell-based model, they seemed more related to the proportion of other CAR types in the formulation than to their λ-type-dependent anti-HPSE activity.


Assuntos
Peróxido de Hidrogênio , Neoplasias , Humanos , Carragenina/farmacologia , Carragenina/química , Peróxido de Hidrogênio/farmacologia , Oligossacarídeos/farmacologia , Oligossacarídeos/química
2.
Mar Drugs ; 21(5)2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37233495

RESUMO

Alginates extracted from two Moroccan brown seaweeds and their derivatives were investigated for their ability to induce phenolic metabolism in the roots and leaves of tomato seedlings. Sodium alginates (ALSM and ALCM) were extracted from the brown seaweeds Sargassum muticum and Cystoseira myriophylloides, respectively. Low-molecular-weight alginates (OASM and OACM) were obtained after radical hydrolysis of the native alginates. Elicitation was carried out by foliar spraying 20 mL of aqueous solutions (1 g/L) on 45-day-old tomato seedlings. Elicitor capacities were evaluated by monitoring phenylalanine ammonia-lyase (PAL) activity, polyphenols, and lignin production in the roots and leaves after 0, 12, 24, 48, and 72 h of treatment. The molecular weights (Mw) of the different fractions were 202 kDa for ALSM, 76 kDa for ALCM, 19 kDa for OACM, and 3 kDa for OASM. FTIR analysis revealed that the structures of OACM and OASM did not change after oxidative degradation of the native alginates. These molecules showed their differential capacity to induce natural defenses in tomato seedlings by increasing PAL activity and through the accumulation of polyphenol and lignin content in the leaves and roots. The oxidative alginates (OASM and OACM) exhibited an effective induction of the key enzyme of phenolic metabolism (PAL) compared to the alginate polymers (ALSM and ALCM). These results suggest that low-molecular-weight alginates may be good candidates for stimulating the natural defenses of plants.


Assuntos
Phaeophyceae , Sargassum , Alga Marinha , Sargassum/química , Alginatos/química , Lignina/farmacologia , Peso Molecular , Phaeophyceae/química , Alga Marinha/química , Estresse Oxidativo
3.
Small ; 18(51): e2204283, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36260830

RESUMO

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.


Assuntos
Ácido Hialurônico , Peptídeos , Polieletrólitos/química , Ácido Hialurônico/química , Nanomedicina
4.
Mar Drugs ; 20(9)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36135735

RESUMO

A novel sulfated xylogalactan (JASX) was extracted and purified from the rhodophyceae Jania adhaerens. JASX was characterized by chromatography (GC/MS-EI and SEC/MALLS) and spectroscopy (ATR-FTIR and 1H/13C NMR) techniques. Results showed that JASX was constituted by repeating units of (→3)-ß-d-Galp-(1,4)-3,6-α-l-AnGalp-(1→)n and (→3)-ß-d-Galp-(1,4)-α-l-Galp-(1→)n substituted on O-2 and O-3 of the α-(1,4)-l-Galp units by methoxy and/or sulfate groups but also on O-6 of the ß-(1,3)-d-Galp mainly by ß-xylosyl side chains and less by methoxy and/or sulfate groups. The Mw, Mn, D, [η] and C* of JASX were respectively 600 and 160 kDa, 3.7, 102 mL.g-1 and 7.0 g.L-1. JASX exhibited pseudoplastic behavior influenced by temperature and monovalent salts and highly correlated to the power-law model and the Arrhenius relationship. JASX presented thixotropic characteristics, a gel-like viscoelastic behavior and a great viscoelasticity character. JASX showed important antioxidant activities, outlining its potential as a natural additive to produce functional foods.


Assuntos
Rodófitas , Alga Marinha , Antioxidantes/química , Antioxidantes/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Rodófitas/química , Sais , Alga Marinha/química , Sulfatos
5.
Biomacromolecules ; 22(4): 1639-1653, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33709706

RESUMO

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.


Assuntos
Antibacterianos , Infecções Estafilocócicas , Antibacterianos/farmacologia , Biofilmes , Humanos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Distribuição Tecidual
6.
Biotechnol Bioeng ; 114(8): 1813-1824, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28398656

RESUMO

The lack of relevant in vitro models for adipose tissue makes necessary the development of a more physiological environment providing spatial and chemical cues for the effective maturation of adipocytes. We developed a biofunctionalized hydrogel with components of adipose extracellular matrix: collagen I, collagen VI, and the cell binding domain of fibronectin and we compared it to usual 2D cultures on plastic plates. This scaffold allowed 3D culture of mature adipocytes from the preadipocytes cell lines 3T3-L1 and 3T3-F442A, as well as primary Human White Preadipocytes (HWP), acquiring in vivo-like organization, with spheroid shaped adipocytes forming multicellular aggregates. The size of these aggregates increased with time up to 120 µm in diameter after 4 weeks of maturation, with good viability. Significantly higher lipogenic activity (up to 20-fold at day 28 for HWP cultures) and differentiation rates were also observed compared to 2D. Gene expression analyses highlighted earlier differentiation and complete maturation of 3D HWP compared to 2D, reinforced by the expression of Perilipin protein after 21 days of nutrition. This increase in adipocytes phenotypic and genotypic markers made this scaffold-driven culture as a robust adipose 3D model. Retinoic acid inhibition of lipogenesis in HWP or isoprenalin and caffeine induction of lipolysis performed on mouse 3T3-F442A cells, showed higher doses of molecules than typically used in 2D, underlying the physiologic relevance of this 3D culture system. Biotechnol. Bioeng. 2017;114: 1813-1824. © 2017 Wiley Periodicals, Inc.


Assuntos
Adipócitos/citologia , Materiais Biomiméticos/química , Microambiente Celular/fisiologia , Proteínas da Matriz Extracelular/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Alicerces Teciduais , Células 3T3-L1 , Adipócitos/fisiologia , Animais , Proliferação de Células/fisiologia , Células Cultivadas , Desenho de Equipamento , Humanos , Camundongos , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos
7.
Biosci Biotechnol Biochem ; 81(10): 1917-1925, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28789591

RESUMO

Microwave-assisted extraction was employed for the isolation of polysaccharides from Posidonia oceanica (PPO). The extracting parameters were optimized adopting response surface methodology. The highest polysaccharide yield (2.55 ± 0.09%), which is in concordance with the predicted value (2.76%), was obtained under the following conditions: extraction time 60 s, liquid-solid ratio of 50:1 (mL/g) and power of 800 W. This polysaccharide, with molecular weight of 524 KDa, characterized by gas chromatography-mass spectrometry showed that PPO was mainly composed of galactose, glucose, and arabinose with molar percentages 25.38, 24.37, and 21.64%, respectively. The pharmacological evaluation of PPO using animal models at the dose of 100 mg/kg indicated a significant anti-inflammatory activity with a percentage of inhibition of edema of 54.65% and a significant antinociceptive activity with 78.91% inhibition of writhing for peripheral analgesic activity and an increase in the hot plate reaction time for central analgesic activity.


Assuntos
Alismatales/química , Fracionamento Químico/métodos , Micro-Ondas , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Ácido Acético/farmacologia , Analgésicos/química , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Edema/tratamento farmacológico , Camundongos , Modelos Teóricos , Polissacarídeos/química , Polissacarídeos/uso terapêutico
8.
Pharm Biol ; 55(1): 156-163, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27650976

RESUMO

CONTENT: Recently, low-molecular-weight hyaluronic acid (LMWHA) has been reported to have novel features, such as free radical scavenging activities, antioxidant activities and dietary supplements. OBJECTIVE: In this study, hyaluronic acid (HA) was extracted from rooster comb and LMWHA was obtained by ultrasonic degradation in order to assess their antioxidant and antiglycation activities. MATERIALS AND METHODS: Molecular weight (Mw) and the content of glucuronic acid (GlcA) were used as the index for comparison of the effect of ultrasonic treatment. The effects on the structure were determined by ultraviolet (UV) spectra and Fourier transform infrared spectra (FTIR). The antioxidant activity was determined by three analytical assays (DPPH, NO and TBARS), and the inhibitory effect against glycated-BSA was also assessed. RESULTS: The GlcA content of HA and LMWHA was estimated at about 48.6% and 47.3%, respectively. The results demonstrate that ultrasonic irradiation decreases the Mw (1090-181 kDa) and intrinsic viscosity (1550-473 mL/g), which indicate the cleavage of the glycosidic bonds. The FTIR and UV spectra did not significantly change before and after degradation. The IC50 value of HA and LWMHA was 1.43, 0.76 and 0.36 mg/mL and 1.20, 0.89 and 0.17 mg/mL toward DPPH, NO and TBARS, respectively. Likewise LMWHA exhibited significant inhibitory effects on the AGEs formation than HA. DISCUSSION AND CONCLUSION: The results demonstrated that the ultrasonic irradiation did not damage and change the chemical structure of HA after degradation; furthermore, decreasing Mw and viscosity of LMWHA after degradation may enhance the antioxidant and antiglycation activity.


Assuntos
Antioxidantes/farmacologia , Galinhas/metabolismo , Crista e Barbelas/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Ácido Hialurônico/farmacologia , Hipoglicemiantes/farmacologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Soroalbumina Bovina/metabolismo , Extratos de Tecidos/farmacologia , Ultrassom , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/química , Estabilidade de Medicamentos , Ácido Glucurônico/isolamento & purificação , Glicosilação , Ácido Hialurônico/química , Ácido Hialurônico/isolamento & purificação , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estrutura Molecular , Peso Molecular , Óxido Nítrico/química , Picratos/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Substâncias Reativas com Ácido Tiobarbitúrico/química , Extratos de Tecidos/química , Extratos de Tecidos/isolamento & purificação , Viscosidade
9.
Biopolymers ; 101(9): 938-44, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24633755

RESUMO

Pullulanase from Klebsiella pneumoniae was entrapped into calcium alginate beads. Its activity was estimated by the determination of number-average molar masses using two different methods: a colorimetric assay of reducing ends (REs) and a size-exclusion chromatography/multiangle light scattering/differential refractive index. The second method also provided weight-average molar masses of hydrolyzed pullulan and the quantity of maltotriose (DP3) and its multiples (DP6 and DP9) produced by the enzymatic treatment. The alginate beads showed a good retention of the loaded pullulanase (30%), and the system showed a downturn of hydrolysis kinetics in comparison with free pullulanase due to the limiting access of substrate-enzyme. On the contrary with the results obtained from free enzyme hydrolysis, for which a large distribution of pullulan fragments is observed during the treatment, the immobilized enzyme system has evidenced, during the enzymatic treatment, the coexistence of native or only slightly degraded pullulan chains together with maltotriose units. Complete hydrolysis of pullulan chains was achieved once diffused into the gel.


Assuntos
Alginatos/química , Enzimas Imobilizadas/metabolismo , Glucanos/metabolismo , Glicosídeo Hidrolases/metabolismo , Microesferas , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Hidrólise , Cinética , Klebsiella/enzimologia , Peso Molecular , Refratometria , Trissacarídeos/química
10.
Carbohydr Polym ; 341: 122330, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38876726

RESUMO

Polyelectrolyte complexes (PECs) were elaborated from chitosan as cationic polymer and carboxy-methylpullulan (CMP), hyaluronic acid (HA) and their derivatives grafted with aminoguaiacol (G) with different degrees of substitution (DSGA) with the aim of obtaining nanogels for drug delivery. For each couple of polysaccharides, the charge ratios giving the smaller size with the lower PDI were selected to produce PECs. CMP_CHIT and CMP-G_CHIT PECs had smaller sizes (220-280 nm) than HA_CHIT and HA-G_CHIT PECs (280-390 nm). PECs were stable at 4 °C during 28 days at pH 5. In phosphate buffer saline (PBS) at pH 7.4, at 4 °C, a better stability of PECs based on CMP-G derivatives was observed. The hydrophobic associations between aminoguaiacol groups (highlighted by measurements of pyrene fluorescence) led to a better PECs' stabilization in PBS. The PECs' antioxidant and antibacterial activities were demonstrated and related to the DSGA. Diclofenac and curcumin were used as drug models: their loading reached 260 and 53 µg/mg PEC, respectively. The release of diclofenac in PBS at 37 °C followed a quasi-Fickian diffusion mechanism with release constant between 0.88 and 1.04 h-1. The curcumin release followed a slow linear increase in PBS/EtOH (60/40 V/V) with an effect of DSGA.


Assuntos
Antibacterianos , Quitosana , Curcumina , Ácido Hialurônico , Ácido Hialurônico/química , Quitosana/química , Quitosana/análogos & derivados , Curcumina/química , Curcumina/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Guaiacol/química , Guaiacol/análogos & derivados , Guaiacol/farmacologia , Diclofenaco/química , Diclofenaco/farmacologia , Portadores de Fármacos/química , Polieletrólitos/química , Sistemas de Liberação de Medicamentos/métodos , Nanogéis/química , Glucanos/química , Escherichia coli/efeitos dos fármacos , Liberação Controlada de Fármacos
11.
J Mater Chem B ; 12(11): 2807-2817, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38404247

RESUMO

Injectable thermosensitive hydrogels based on hyaluronic acid (HA) grafted with lower critical solution temperature (LCST) polyoxazoline (copolymers of poly(isopropyl-co-butyl oxazoline)) or P(iPrOx-co-BuOx) have been elaborated with tunable solution/gel temperature transitions and gel state elastic modulus. A suitable HA-g-P(iPrOx-co-BuOx-67/33)-0.10 sample with an iPrOx/BuOx ratio of 67/33, a polymerization degree (DP) of 25, a substitution degree (DS) of 10%, and displaying thermally induced gelling character with elastic (G') and viscous (G'') moduli crossover points at 25 °C and a G' at 37 °C around 80 Pa has been chosen for medical application. Hydrogels obtained with HA-g-P(iPrOx-co-BuOx-67/33)-0.10 exhibited high stability at 37 °C and excellent injectability properties with full and quick reversibility. The incorporation of a secondary network (HA), until 35 wt%, into the thermosensitive hydrogel also demonstrated very good stability and injectability.


Assuntos
Ácido Hialurônico , Hidrogéis , Polímeros , Temperatura
12.
Int J Biol Macromol ; 277(Pt 3): 134302, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39094866

RESUMO

Allium roseum is amongst the most important wild medicinal plants. It is known for its diverse biological properties, including antioxidant, antibacterial and antidiabetic activities. In this work, the polysaccharides (PARLs) were ultrasonically extracted from Allium roesum leaves then purified and analyzed by several techniques. Chemical composition and GC-MS analysis showed that the obtained polysaccharides were composed mainly of glucose (40.20 %), mannose (25.30 %), fructose (10.60 %) and galacturonic acid (15.11 %). Moreover, PARLs exhibited a potent antioxidant effect with higher capacities up to 69.61 % and 71.72 % for DPPH and ABTS free radicals, respectively. Furthermore, PARLs significantly modulated inflammatory response by reducing TNF-α, IL-6, and IL-8 pro-inflammatory mediators and promoting the anti-inflammatory IL-10 mediator in LPS stimulated THP-1 derived macrophages. The in-vivo tests proved that the extract was able to decrease carrageenan-induced rat paw swelling by around 68.15 % after 4 h of treatment. PARLs, significantly reduced the growth of U87 (glioblastoma) and IGROV-1 cancer cells with IC50 values of about 4.27 and 7.89 mg/mL respectively. This research clearly shows that Allium roseum polysaccharides can be used as natural antioxidants with anti-inflammatory and anticancer properties.

13.
3 Biotech ; 14(3): 92, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38425411

RESUMO

Polysaccharide-rich materials were extracted from the alcohol-insoluble solids of Olea europaea l. **leaves. Structural characteristics were determined by colorimetric techniques, FT-IR, GC-MS, SEC/MALS/VD/DRI, and NMR (1H,13C). The extract and its main macromolecular components were characterized to assess their ability toward antioxidant, α-amylase inhibition, and antiproliferative activities. Results revealed that the ultrasound olive leave extract comprises polysaccharides with uronic acid, galactose, arabinose, and glucose in molar percentages of 11.7%, 11.3%, 7.5%, and 4.9% respectively, constituting 41% of the total mass. In addition, polyphenols (21%) and proteins (9%) are associated with these polysaccharides. Further, the extract showed noticeable ORAC and free radical scavenging abilities, in addition to high in vitro antiproliferative activity against Caco-2 colon carcinoma cell lines. Similarly, the extract exhibited a strong, uncompetitive inhibition of α-amylase by 75% in the presence of the extract with 0.75 µg/mL of concentration. This research concludes that ultrasound extraction method can be used for the extraction of polysaccharide-polyphenol-protein complexes. These conjugates exhibit the potential for combined biological activities resulting from a synergistic effect of its compounds, making them promising ingredients for the development of functional food.

14.
Bioengineered ; 15(1): 2296257, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38153265

RESUMO

With the aim to find new polysaccharides of rheological interest with innovated properties, rhamnofucans produced as exopolysaccharides (EPS) in a photobioreactor (PBR) and an airlift bioreactor (ABR) by the marine microalgae Glossomastix sp. RCC3707 and RCC3688 were fully studied. Chemical characterizations have been conducted (UHPLC - MS HR). Analyses by size-exclusion chromatography (SEC) coupled online with a multiangle light scattering detector (MALS) and a differential refractive index detector showed the presence of large structures with molar masses higher than 106 g.mol-1. The rheological studies of these EPS solutions, conducted at different concentrations and salinities, have evidenced interesting and rare behavior characteristic of weak and fragile hydrogels i.e. gel behavior with very low elastic moduli (between 10-2 and 10 Pa) and yield stresses (between 10-2 and 2 Pa) according to the EPS source, concentration, and salinity. These results were confirmed by diffusing wave spectroscopy. Finally, as one of potential application, solutions of EPS from Glossomastix sp. have evidenced very good properties as anti-settling stabilizers, using microcrystalline cellulose particles as model, studied by multiple light scattering (MLS) with utilization in cosmetic or food industry. Compared to alginate solution with same viscosity for which sedimentation is observed over few hours, microalgae EPS leads to a stable suspension over few days.


Assuntos
Microalgas , Polissacarídeos/química , Alginatos , Fotobiorreatores , Polissacarídeos Bacterianos
15.
Int J Biol Macromol ; 264(Pt 1): 130424, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428772

RESUMO

The fishing and aquaculture industries generate a huge amount of waste during processing and preservation operations, especially those of tuna. Recovering these by-products is a major economic and environmental challenge for manufacturers seeking to produce new active biomolecules of interest. A new hyaluronic acid was extracted from bluefin tuna's vitreous humour to assess its antioxidant and pharmacological activities. The characterization by infrared spectroscopy (FT-IR), nuclear magnetic resonance ((1D1H) and 2D (1H COSY, 1H/13C HSQC)) and size exclusion chromatography (SEC/MALS/DRI/VD) revealed that the extracted polysaccharide was a hyaluronic acid with high uronic acid content (55.8 %) and a weight average molecular weight of 888 kDa. This polymer possesses significant anti-radical activity and ferrous chelating capacity. In addition, pharmacological evaluation of its anti-inflammatory and analgesic potential, using preclinical models, in comparison with reference drugs (Dexamethasone, diclofenac, and acetylsalicylate of lysine), revealed promising anti-inflammatory activity as well as interesting peripheral and central antinociceptive activity. Therefore, our new hyaluronic acid compound may therefore serve as a potential drug candidate for the treatment of pain sensation and inflammation of various pathological origins.


Assuntos
Ácido Hialurônico , Atum , Animais , Espectroscopia de Infravermelho com Transformada de Fourier , Polissacarídeos/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química
16.
Biomacromolecules ; 14(7): 2234-41, 2013 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-23713899

RESUMO

The behavior of a hydrolytic enzyme (pullulanase) toward its substrate (pullulan) in the presence of a nonsubstrate (alginate), both below and above the critical entanglement concentration (C*), was studied. The hydrolysis kinetics were studied with the enzyme and alginate concentrations varied using two main methods: a colorimetric assay of the reducing extremities (RE), which allowed the number-average molar masses (Mn) of the oligosaccharides to be determined, and size exclusion chromatography with on-line, multiangle light scattering, viscometer, and differential refractive index detectors, which allowed the average molar masses, Mn and Mw, of the oligosaccharides during hydrolysis to be determined. Free pullulanase acts via an "endo" process. The presence of alginate slows the hydrolysis kinetics, particularly when the alginate concentration is greater than the C*. These results were confirmed by the evolution of the kinetic parameters (KM, Vmax) obtained via isothermal titration calorimetry (ITC). The amount of oligosaccharides produced is not dependent on the alginate concentration, and the endo enzyme behavior is not modified by the entanglement in the medium. These observations were also confirmed by ITC analysis in the presence of degraded alginate (without entanglement). Our results correlated with the substrate diffusion in entangled media. The pullulanase reaction in the presence of alginate is shown to be diffusion-dependent.


Assuntos
Alginatos/química , Glucanos/química , Glicosídeo Hidrolases/química , Calorimetria , Cromatografia em Gel , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Hidrólise , Cinética , Oligossacarídeos/metabolismo
17.
Antibiotics (Basel) ; 12(6)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37370385

RESUMO

The poor bioavailability of antibiotics at infection sites is one of the leading causes of treatment failure and increased bacterial resistance. Therefore, developing novel, non-conventional antibiotic delivery strategies to deal with bacterial pathogens is essential. Here, we investigated the encapsulation of two fluoroquinolones, ciprofloxacin and levofloxacin, into polymer-based nano-carriers (nano-antibiotics), with the goal of increasing their local bioavailability at bacterial infection sites. The formulations were optimized to achieve maximal drug loading. The surfaces of nano-antibiotics were modified with anti-staphylococcal antibodies as ligand molecules to target S. aureus pathogens. The interaction of nano-antibiotics with the bacterial cells was investigated via fluorescent confocal microscopy. Conventional tests (MIC and MBC) were used to examine the antibacterial properties of nano-antibiotic formulations. Simultaneously, a bioluminescence assay model was employed, revealing the rapid and efficient assessment of the antibacterial potency of colloidal systems. In comparison to the free-form antibiotic, the targeted nano-antibiotic exhibited enhanced antimicrobial activity against both the planktonic and biofilm forms of S. aureus. Furthermore, our data suggested that the efficacy of a targeted nano-antibiotic treatment can be influenced by its antibiotic release profile.

18.
Pharmaceutics ; 15(3)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36986789

RESUMO

The lyophilization of nanogels is practical not only for their long-term conservation but also for adjusting their concentration and dispersant type during reconstitution for different applications. However, lyophilization strategies must be adapted to each kind of nanoformulation in order to minimize aggregation after reconstitution. In this work, the effects of formulation aspects (i.e., charge ratio, polymer concentration, thermoresponsive grafts, polycation type, cryoprotectant type, and concentration) on particle integrity after lyophilization and reconstitution for different types of polyelectrolyte complex nanogels (PEC-NGs) from hyaluronic acid (HA) were investigated. The main objective was to find the best approach for freeze-drying thermoresponsive PEC-NGs from Jeffamine-M-2005-functionalized HA, which has recently been developed as a potential platform for drug delivery. It was found that freeze-drying PEC-NG suspensions prepared at a relatively low polymer concentration of 0.2 g.L-1 with 0.2% (m/v) trehalose as a cryoprotectant allow the homogeneous redispersion of PEC-NGs when concentrated at 1 g.L-1 upon reconstitution in PBS without important aggregation (i.e., average particle size remaining under 350 nm), which could be applied to concentrate curcumin (CUR)-loaded PEC-NGs for optimizing CUR content. The thermoresponsive release of CUR from such concentrated PEC-NGs was also reverified, which showed a minor effect of freeze-drying on the drug release profile.

19.
Curr Drug Deliv ; 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37680160

RESUMO

INTRODUCTION: In recent decades, drug delivery applications have extensively utilized hydrogel systems based on natural polymers. Among the numerous biopolymer-based hydrogel drug delivery systems reported, a novel pectin-like substance was extracted from fig leaves and copolymerized with chitosan. METHOD: The hydrogel was reformed into microspheres using glutaraldehyde (chemical cross-linker) and sodium hexametaphosphate (physical cross-linker). The extracted polysaccharide and the prepared hydrogels were characterized by FTIR, GC/MS, SEC/MALS/DRI as well as XRD, SEM, BET, and thermal analysis. SEM images revealed the formation of porous microspheres with an average size of 50 µm in diameter. Degrees of swelling in pH7 at 35°C have shown the hydrogels reached two to three times their weights. This has been reflected in their ability to load drugs or any other chemicals. The loading formula shows that hydrogels have maximum loading efficiency more than one-third of the weight of hydrogel. The antimicrobial ciprofloxacin was used as a model for loading on prepared hydrogels. The loaded hydrogels were tested for their biological activities against staphylococcus aureus (S. aureus) bacteria. The antimicrobial growth inhibition zone of the cultured (S. aureus) by ciprofloxacin-loaded hydrogel was followed, which shows controlled growth in inhibition zone sizes and for long time intervals. Results showed that the pectin-chitosan hydrogels exhibited significant antibacterial activity against gram - positive bacteria (S. aureus), with an inhibition zone of 45 mm for (CH-co-FLP)/GLU hydrogel. RESULT: In vitro, the ciprofloxacin-loaded hydrogels were studied and the cumulative release of ciprofloxacin under suitable conditions was found in a controlled manner and kept release for a long time interval. Data exhibited that the cumulative release profile of ciprofloxacin from the hydrogel demonstrated sustained release over 48 hours, with a value of 6.9% released within the first 24 hours and 7.0 and 6.9% % released at the end of the study for the (CH-co-FLP)/GLU and (CH-co-FLP)/SMP hydrogels, respectively. CONCLUSION: The novel pectin-chitosan hydrogels hold the potential to enhance the quality of life for numerous patients by minimizing the need for frequent intake of chronic medications.

20.
Antioxidants (Basel) ; 12(2)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36830010

RESUMO

Coriandrum sativum is one of the most widespread curative plants in the world, being vastly cultivated in arid and semi-arid regions as one of the oldest spice plants. The present study explored the extraction of polysaccharides from Coriandrum sativum seeds and the evaluation of their antioxidant potential and hepatoprotective effects in vivo. The polysaccharide from coriander seeds was extracted, and the structural characterization was performed by FT-IR, UV-vis, DSC, NMR (1D and 2D), GC-MS, and SEC analysis. The polysaccharide extracted from Coriandrum sativum (CPS) seeds was characterized to evaluate its antioxidant and hepatoprotective capacities in rats. Results showed that CPS was composed of arabinose, rhamnose, xylose, mannose, fructose, galactose, and glucose in molar percentages of 6.2%, 3.6%, 8.8%, 17.7%, 5.2%, 32.9%, and 25.6%, respectively. Further, CPS significantly hindered cadmium-induced oxidation damage and exercised a protective effect against Cd hepatocytotoxicity, with a considerable reduction in MDA production and interesting CAT and SOD enzyme levels. Results suggest that CPS might be employed as a natural antioxidant source.

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