Potential of amphiphilically modified low molecular weight chitosan as a novel carrier for hydrophobic anticancer drug: Synthesis,characterization, micellization and cytotoxicity evaluation

Amphiphilically modified low molecular weight chitosan (LMWC) with long chain alkyl groups as hydrophobic moieties and carboxymethyl groups as hydrophilic moieties (N-octyl-N,O-carboxymethyl LMWC, OC-LMWC) was synthesized. Self-assembled polymeric micelles of OC-LMWC were prepared in aqueous environment. Critical micelle concentrations (CMC) of OC-LMWCs were varied from 8.7 to 27.7 mg/l. Paclitaxel (PTX) was successfully encapsulated into the hydrophobic cores of the nanoparticles. The drug loading content and entrapment efficiency were higher to 32.17% (w/w) and 80.61%, respectively. Differential scanning calorimetry (DSC), transmission electron microscope (TEM) observation and dynamic light scattering (DLS) measurements were carried out to determination the physicochemical properties of the micelles. MTT assay showed that the in vitro cytotoxic effect of the PTX-loaded micelles was comparable to that of the commercial formulation, but the blank micelles were far less than the Cremophor EL^® vehicle. These results suggested that OC-LMWC micelles were promising carriers for hydrophobic anticancer agents.     

Microspheres of chitosan/carboxymethyl cashew gum (CH/CMCG): Effect of chitosan molar mass and CMCG degree of substitution on the swelling and BSA release

Chitosan/carboxymethyl cashew gum microspheres (CH/CMCG) were prepared with carboxymethyl cashew gum with two different degrees of substitution (DS) and loaded with bovine serum albumin (BSA). In water, for microspheres formed using low molar mass chitosan (LCH) sample swelling was observed for both CMCG samples and CMCG sample with higher DS showed greater swelling. Using high molar mass chitosan (HCH) sample swelling was observed only for microsphere with high DS of CMCG (DS = 0.44). At pH 7.4, the HCH sample led to a lower degree of swelling. The diffusion coefficients D_v were higher for the higher DS of CMCG in both media and the HCH sample had a lower D_v than LCH one. Faster BSA release rates were observed for beads prepared with the higher DS, whereas those prepared with DS = 0.16 took twice the time to reach similar release profiles. All microsphere systems investigated had a non-Fickian BSA release mechanism.     

Physicochemical characterization of chitin and chitosan from crab shells

Crab chitosan was prepared by alkaline N-deacetylation of crab chitin for 60, 90 and 120 min and the yields were 30.0-32.2% with that of chitosan C120 being the highest. The degree of N-deacetylation of chitosans (83.3–93.3%) increased but the average molecular weight (483–526 kDa) decreased with the prolonged reaction time. Crab chitosans showed lower lightness and WI values than purified chitin, chitosans CC and CS but higher than crude chitin. With the prolonged reaction time, the nitrogen (8.9–9.5%), carbon (42.2–45.2%) and hydrogen contents (7.9–8.6%) in chitosans prepared consistently increased whereas N/C ratios remained the same (0.21). Crab chitosans prepared showed a melting endothermic peak at 152.3–159.2 °C. Three chitosans showed similar microfibrillar crystalline structure and two crystalline reflections at 2θ = 8.8–9.0° and 18.9–19.1°. Overall, the characteristics of three crab chitosans were unique and differed from those of chitosan CC and CS as evidenced by the element analysis, differential scanning calorimetry, scanning electron microscopy and X-ray diffraction patterns.     

Polyelectrolyte complexes of gum kondagogu and chitosan,as diclofenac carriers

Polyelectrolyte complexes (PEC) of gum kondagogu (GKG) and chitosan were prepared by mixing polymeric solutions of different concentrations (0.02–0.18% w/v). The complex formed were loaded with diclofenac sodium, and the release of the drug was measured in vitro and in vivo, along with the measurement of particle size, zeta potential, complex formation, flow properties, and loading efficiency. Maximum yield of PEC was observed at gum kondagogu concentrations above 80%. The PEC showed lower release of diclofenac sodium in 0.1 N HCl as compared to phosphate buffer (pH 6.8). Increasing the concentration of gum kondagogu in PEC led to an increase in drug release. However, PEC 1:3 (gum kondagogu: chitosan) with higher concentration of chitosan showed 98% release with in 4.5 h, owing to the fact that chitosan has a higher degree of swelling in acidic medium. PEC 5:1 and 3:1 showed a 5.3- and 5.8-fold increase in relative bioavailability compared to the free drug when administered orally to the rats.     

Antifungal potentiality of mycogenic silver nanoparticles capped with chitosan produced by endophytic Amesia atrobrunnea

This research reports the fabrication of silver nanoparticles (AgNPs) from endophytic fungus, Amesia atrobrunnea isolated from Ziziphus spina-christi (L.). Influencing factors for instance, thermal degree of incubation, media, pH, and silver nitrate (AgNO₃) molarity were optimized. Then, the AgNPs were encapsulated with chitosan (Ch-AgNPs) under microwave heating at 650 W for 90 s. Characterization of nanoparticles was performed via UV–visible (UV–vis) spectrophotometer, Fourier-transform infrared spectrophotometer (FTIR), zeta potential using dynamic-light scattering (DLS), and field-emission-scanning electron microscope (FE-SEM). Anti-fungal activity of Ch-AgNPs at (50, 25, 12.5, 6.25 mg/L) was tested against Fusarium oxysporum, Curvularia lunata, and Aspergillus niger using the mycelial growth inhibition method (MGI). Results indicated that Czapek-dox broth (CDB) with 1 mM AgNO₃, an acidic pH, and a temperature of 25–30 °C were the optimum for AgNPs synthesis. (UV–vis) showed the highest peak at 435 nm, whereas Ch-AgNPs showed one peak for AgNPs at 405 nm and another peak for chitosan at 230 nm. FTIR analysis confirmed that the capping agent chitosan was successfully incorporated and interacted with the AgNPs through amide functionalities. Z-potential was −19.7 mV for AgNPs and 38.9 mV for Ch-AgNPs, which confirmed the significant stability enhancement after capping. FES-SEM showed spherical AgNPs and a reduction in the nanoparticle size to 44.65 nm after capping with chitosan. The highest mycelial growth reduction using fabricated Ch-AgNPs was 93% for C. lunata followed by 77% for A. niger and 66% F. oxysporum at (50 mg/L). Biosynthesis of AgNPs using A. atrobrunnea cell-free extract was successful. Capping with chitosan exhibited antifungal activity against fungal pathogens.     

Chitosan microcapsules loaded with either miconazole nitrate or clotrimazole,prepared via emulsion technique

In this paper, a simple and versatile coacervation technique has been developed by using an ultrasound-assisted oil/water emulsion method for the preparation of antifungal agent-loaded microcapsules. Two types of chitosan microcapsules are successfully prepared. The mean particle size of the chitosan/miconazole nitrate microcapsules is 2.6 μm and that of the chitosan/clotrimazole microcapsules is 4.1 μm. The encapsulation efficiency of the chitosan/miconazole nitrate microcapsules (77.58–96.81%) is relatively higher than that of the chitosan/clotrimazole microcapsules (56.66–93.82%). The in vitro drug release performance of the microcapsules shows that the chitosan/miconazole nitrate microcapsules release about 49.5% of the drug while chitosan/clotrimazole microcapsules release more than 66.1% of the drug after 12 h under a pressure of 5 kg at pH 5.5, which is similar to the pH of human skin. The prepared drug-loaded microcapsules could be applied onto bandages or socks, and will continuously release antifungal drugs in a controlled manner under pressure.     

Preparation of gold nanopowders and nanoparticles using chitosan suspensions

Simple methods for preparation of gold nanopowders and nanoparticles are reported. Gold/chitosan nanoparticles were prepared by using basic chitosan suspension as a dispersant and as a reductant. The resulting nanoparticles were processed by pyrolysis and thus obtain black gold nanopowder. The FESEM images indicate that most diameters of the nanopowder prepared were in the range of 50 and 200 nm. Hydrolysis is another quick decomposition method for chitosan. Acetic acid was adopted to implement the hydrolysis. The AEM images of the auberginic suspension show that the average gold nanoparticle diameter was less than 40 nm with good dispersion. Use of chitosan suspensions can produce gold nanopowder as well as gold nanoparticle without using toxic organic chemicals.     

Improved reproducibility in the determination of the molecular weight of chitosan by analytical size exclusion chromatography

The reproducibility of the determination of the molecular weight of chitosans in the 90–210 kDa range (M_n) by analytical size exclusion chromatography with multi-angle laser light scattering (SEC-MALLS) was improved by reducing the salt concentration in the mobile phase from (0.3 M acetic acid, 0.2 M sodium acetate, and 0.8 mM sodium azide) to (0.15 M acetic acid, 0.1 M sodium acetate, and 0.4 mM sodium azide) using Tosoh TSKgel G6000PW_XL and G5000PW_XL columns in series. The variability of measured molecular weight was significantly reduced by lowering the acetate concentration in the mobile phase, while the average molecular weight did not change significantly. The coefficient of variation of the number-average molecular weight, CV(M_n), decreased from 7–12% to 3–6% upon mobile phase dilution. This reduced variability in molecular weight of chitosans obtained from SEC is a significant improvement when precise values of chitosan molecular weight are required, for example in stability studies where viscosity changes in concentrated chitosan solutions are assessed, and in gene delivery applications.     

Development and <Emphasis Type="Italic">In Vitro</Emphasis> Characterization of Galactosylated Low Molecular Weight Chitosan Nanoparticles Bearing Doxorubicin

The aim of the present research was to evaluate the potential of galactosylated low molecular weight chitosan (Gal-LMWC) nanoparticles bearing positively charged anticancer, doxorubicin (DOX) for hepatocyte targeting. The chitosan from crab shell was depolymerized, and the lactobionic acid was coupled with LMWC using carbodiimide chemistry. The depolymerized and galactosylated polymers were characterized. Two types of Gal-LMWC(s) with variable degree of substitution were employed to prepare the nanoparticles using ionotropic gelation with pentasodium tripolyphosphate anions. Factors affecting nanoparticles formation were discussed. The nanoparticles were characterized by transmission electron microscopy and photon correlation spectroscopy and found to be spherical in the size range 106–320 nm. Relatively higher percent DOX entrapment was obtained for Gal-LMWC(s) nanoparticles than for LMWC nanoparticles. A further increase in drug entrapment was found with nanoparticles prepared by Gal-LMWC with higher degree of substitution. A hypothesis which correlates the ionic concentration of DOX in nanoparticles preparation medium and percent DOX entrapment in cationic polymer has been proposed to explain the enhanced DOX entrapment. In-vitro drug release study demonstrated an initial burst release followed by a sustained release. The targeting potential of the prepared nanoparticles was assessed by in vitro cytotoxicity study using the human hepatocellular carcinoma cell line (HepG₂) expressing the ASGP receptors on their surfaces. The enthusiastic results showed the feasibility of Gal-LMWC(s) to entrap the cationic DOX and targeting potential of developed Gal-LMWC(s) nanoparticles to HepG₂ cell line.     

Upgrading the preparation of high-quality chitosan from Procambarus clarkii wastes over the traditional isolation of shrimp chitosan

Crustacean waste is one of the most severe issues, posing significant environmental and health risks. This study aims to improve managing marine waste by isolating chitosan from Procambarus clarkii by devising a new methodology, incorporating technical steps, e.g., washing, decolorization and deacetylation under a reflexive condenser and dialysis purification. A comparison was made between the prepared P. clarkii chitosan and four types of shrimp chitosans: commercial, high, low, and nano. The obtained chitosan has a low molecular weight and viscosity compared to the commercial shrimp chitosan used in various applications. P. clarkii chitosan was prepared in high quality from a cheap source, as its color and quality were better than those of the commercial shrimp chitosan. The new methodology has successfully extracted chitosan from P. clarkii in a good quality and high purity, achieving 89% deacetylation, high solubility, high purity, and medium molecular weight. Analysis of the different chitosan samples with Fourier transform infrared spectroscopy (FTIR), atomic force microscopy, Raman spectrum referred indicated high similarity between the chitosan different types, regardless of its source. The 3D image of P. clarkii showed the distance between the highest and most profound points of extracted chitosan is 728.94 nm, revealing homogeneous, smooth surfaces, apparently free of pores and cracks. FTIR and Raman spectrum of P. clarkii indicated various functional groups, e.g., alcohol, amines, amides, and phenols. These active groups are responsible for about 60% of the antioxidant activity of that product. Evaluating the quality traits indicated the excellence of the chitosan prepared from P. clarkii, especially in color, viscosity, and antioxidant activity, nominating it for different food applications.     

Dietary supplementation of green synthesized manganese-oxide nanoparticles and its effect on growth performance,muscle composition and digestive enzyme activities of the giant freshwater prawn Macrobrachium rosenbergii

The green synthesized Mn₃O₄ nanoparticles (manganese-oxide nanoparticles) using Ananas comosus (L.) peel extract was characterized by various techniques. HR-SEM photograph showed that manganese-oxide nanoparticles (Mn-oxide NPs) were spherical in shape, with an average size of 40–50 nm. The Zeta potential revealed the surface charge of Mn-oxide NPs to be negative. Further, the Mn-oxide NPs were dietary supplemented for freshwater prawn Macrobrachium rosenbergii. The experimental basal diets were supplemented with Mn-oxide NPs at the rates of 0 (control), 3.0, 6.0, 9.0, 12, 15 and 18 mg/kg dry feed weight. The as-supplemented Mn-oxide NPs were fed in M. rosenbergii for a period of 90 days. The experimental study demonstrated that prawns fed with diet supplemented with 3–18 mg Mn-oxide NPs/kg shows enhanced (P < 0.05) growth performance, including final weight and weight gain (WG). Significant differences (P < 0.05) in feed conversion ratio (FCR) were observed in prawn fed with different diets. Additionally, prawns fed with 3.0–18 mg/kg Mn-oxide NPs supplemented diets achieved significant (P < 0.05) improvement in growth performance, digestive enzyme activities and muscle biochemical compositions, while, the prawns fed with 16 mg/kg of Mn-oxide NPs showed enhanced performance. Prawns fed on diet supplemented with 16 mg/kg Mn-oxide NPs showed significantly (P < 0.05) higher total protein level. The antioxidants enzymatic activity (SOD and CAT) metabolic enzymes status in muscle and hepatopancreas showed no significant (P > 0.05) alterations in prawns fed with 3.0–18 mg/kg of Mn-oxide NPs supplemented diets. Consequently, the present work proposed that 16 mg/kg of Mn-oxide NPs could be supplemented for flexible enhanced survival, growth and production of M. rosenbergii. Therefore, the data of the present study recommend the addition of 16 mg/kg of Mn-oxide NPs diet to developed prawn growth and antioxidant defense system.     

Insulin-releasing and cytotoxic properties of the frog skin peptide,tigerinin-1R: a structure–activity study

The frog skin host-defense peptide tigerinin-1R (RVCSAIPLPICH.NH₂) is insulinotropic both in vitro and in vivo. This study investigates the effects on insulin release and cytotoxicity of changes in cationicity and hydrophobicity produced by selected substitutions of amino acids by l-arginine, l-lysine and l-tryptophan. The [A5W], [L8W] and [I10W] analogs produced a significant (P < 0.01) increase in the rate of insulin release from BRIN-BD11 rat clonal β cells at concentration of 0.01 nM compared with 0.1 nM for tigerinin-1R. The increase in the rate of insulin release produced by a 3 μM concentration of the [S4R], [H12K], and [I10W] analogs from both BRIN-BD11 cells and mouse islets was significantly greater (P < 0.05) than that produced by tigerinin-1R. No peptide stimulated the release of lactate dehydrogenase at concentrations up to 3 μM indicating that plasma membrane integrity had been preserved. [A5W] tigerinin-1R was the only analog tested that showed cytotoxic activity against human erythrocytes (LC₅₀ = 265 ± 16 μM) and inhibited growth of Escherichia coli (MIC = 500 μM) and Staphylococcus aureus (MIC = 250 μM). The circular dichroism spectra of tigerinin-1R and [A5W] tigerinin-1R indicate that the peptides adopt a mixture of β-sheet, random coil and reverse β-turn conformations in 50% trifluoroethanol/water and methanol/water. Administration of [S4R] tigerinin-1R (75 nmol/kg body weight) to high-fat fed mice with insulin resistance significantly (P < 0.05) enhanced insulin release and improved glucose tolerance over a 60 min period following an intraperitoneal glucose load. The study supports the claim that tigerinin-1R shows potential for development into novel therapeutic agents for treatment of type 2 diabetes mellitus.     

Hyaluronic acid interaction with chitosan-conjugated magnetite particles and its purification

The polyelectrolyte complex (PEC) effect between hyaluronic acid (HA) and chitosan was explored to recover HA from fermentation broth. Chitosan was conjugated with the magnetic nanoparticles by co-precipitation method to facilitate its recovery. The magnetic chitosan particles (chitosan–magnetite) have an average size about 5 μm and point of zero charge (PZC) around 6.5. pH lower than PZC favored the HA capture. About 39 mg of HA was captured per gram of particles at pH 6. Nearly quantitative release of captured HA was achieved at pH 8. Although HA could not be directly isolated from Streptococcus zoopedemics fermentation broth by manipulating pH between 6 and 8, HA free of contaminant protein could be purified from the crude ethanol precipitate using chitosan–magnetite.     

Cross-linking chitosan into UV-irradiated cellulose fibers for the preparation of antimicrobial-finished textiles

Chitosan cross-linked cellulose fibers were prepared using non-toxic procedures in order to confer antimicrobial properties to cellulose fibers. Citric acid was used as the cross-linker and NaH₂PO₄ as catalyst in previously UV-irradiated cellulose fibers. Further heat dried-cure process and washing with detergent, water and acetic acid (0.1 M) gave a maximum incorporation of chitosan of 27 mg per gram of functionalized textile. The thermogravimetric analysis of the material with the highest chitosan content showed an increased thermal stability compared to cellulose and chitosan. The UV-irradiation induced morphological changes, such as less entangled cellulose fibers, as observed by scanning electron microscopy, which was prompted to enhance the chitosan incorporation. The biomass and spore germination percentage of Penicillium chrysogenum and colony forming units per millilitre for Escherichia coli decreased significantly on the composed materials as compared to raw cellulose fiber and it was similar to that obtained with a commercial antimicrobial cellulose fiber.     

Tracing transport of chitosan nanoparticles and molecules in Caco-2 cells by fluorescent labeling

The aim of this study was to explore the transport properties of chitosan nanoparticles and molecules in Caco-2 cells. Fluorescein isothiocyanate-labeled chitosan (f-CS) was synthesized and prepared into nanoparticles (f-CNP). The f-CNP exhibit a mean size of 58.04 nm and a mean charge with +41.63 mV. Cytotoxicities of the f-CNP and the f-CS against Caco-2 cells were disregarded in the transport study. The transport was observed under fluorescence microscope. The f-CNP could be transported into Caco-2 cells across the cell membrane, and showed concentration-dependent and saturable intracellular fluorescence signal at 37 °C. Meanwhile, the energy-dependence of the trans-membrane transport of f-CNP was not observed at 4 °C. The f-CS was mainly accumulated in the cell peripheral and showed a concentration-dependent intercellular fluorescence signal. Thus, formulation of chitosan into nanoparticles significantly improved its trans-membrane transport in Caco-2 cells.     

Exenatide-loaded PLGA microspheres with improved glycemic control: In vitro bioactivity and in vivo pharmacokinetic profiles after subcutaneous administration to SD rats

A subcutaneous exenatide delivery system was developed and characterized in vitro and in vivo. The results clearly showed that the exenatide loaded PLGA microspheres prepared by using a non-aqueous processing medium had low burst release and high drug encapsulation efficiency. Exenatide loaded in the microspheres preserved its bioactivity. The pharmacokinetics parameters were determined after subcutaneous administration of microspheres to SD rats. The plasma concentration of the single dose of the sustained-release microspheres attained C_max of 108.19 ± 14.92 ng/ml at t_max of 1.33 ± 0.58 h and the t_1/2 was 120.65 ± 44.18 h. There was a linear correlation between the in vitro and in vivo release behavior (R² = 0.888). Exenatide loaded microspheres may prove to have great potential for clinical use.     

Peptide-based hydrogel nanoparticles as effective drug delivery agents

Peptide-based hydrogel nanoparticles represent a promising alternative to current drug delivery approaches. We have previously demonstrated that the Fmoc-FF aromatic dipeptide building block can self-assemble in aqueous solutions to form nano-scaled ordered hydrogels of remarkable mechanical rigidity. Here, we present a scalable process for the assembly of this peptide into hydrogel nanoparticles (HNPs) aimed to be utilized as potential drug delivery carriers. Fmoc-FF based HNPs were formulated via modified inverse-emulsion method using vitamin E-TPGS as an emulsion stabilizer and high speed homogenization. The formed HNPs exhibited two distinguishable populations with an average size of 21.5 ± 1.3 and 225.9 ± 0.8 nm. Gold nanoparticles were encapsulated within the hydrogel nanoparticles as contrast agents to monitor the formation of the assemblies and their ultrastructural properties. Next, we demonstrated a robust experimental procedure developed and optimized for the formulation, purification, storage and handling procedures of HNPs. Encapsulation of doxorubicin (Dox) and 5-flourouracil (5-Fu) within the HNPs matrix showed release kinetics of the drugs depending on their chemical structure, molecular weight and hydrophobicity. The results clearly indicate that Fmoc-FF based hydrogel nanoparticles have the potential to be used as encapsulation and delivery system of various drugs and bioactive molecules.     

Stress-induced dissociations between intracellular calcium signaling and insulin secretion in pancreatic islets

In healthy pancreatic islets, glucose-stimulated changes in intracellular calcium ([Ca²⁺]_i) provide a reasonable reflection of the patterns and relative amounts of insulin secretion. We report that [Ca²⁺]_i in islets under stress, however, dissociates with insulin release in different ways for different stressors. Islets were exposed for 48 h to a variety of stressors: cytokines (low-grade inflammation), 28 mM glucose (28G, glucotoxicity), free fatty acids (FFAs, lipotoxicity), thapsigargin (ER stress), or rotenone (mitochondrial stress). We then measured [Ca²⁺]_i and insulin release in parallel studies. Islets exposed to all stressors except rotenone displayed significantly elevated [Ca²⁺]_i in low glucose, however, increased insulin secretion was only observed for 28G due to increased nifedipine-sensitive calcium-channel flux. Following 3–11 mM glucose stimulation, all stressors substantially reduced the peak glucose-stimulated [Ca²⁺]_i response (first phase). Thapsigargin and cytokines also substantially impacted aspects of calcium influx and ER calcium handling. Stressors did not significantly impact insulin secretion in 11 mM glucose for any stressor, although FFAs showed a borderline reduction, which contributed to a significant decrease in the stimulation index (11:3 mM glucose) observed for FFAs and also for 28G. We also clamped [Ca²⁺]_i using 30 mM KCl + 250 μM diazoxide to test the amplifying pathway. Only rotenone-treated islets showed a robust increase in 3–11 mM glucose-stimulated insulin secretion under clamped conditions, suggesting that low-level mitochondrial stress might activate the metabolic amplifying pathway. We conclude that different stressors dissociate [Ca²⁺]_i from insulin secretion differently: ER stressors (thapsigargin, cytokines) primarily affect [Ca²⁺]_i but not conventional insulin secretion and ‘metabolic’ stressors (FFAs, 28G, rotenone) impacted insulin secretion.     

Efficient digestion of chitosan using chitosanase immobilized on silica-gel for the production of multisize chitooligosaccharides

Chitosanase-coated silica-gels were prepared via cross-linking of the chitosanase onto silica-gels for the efficient production of multisize chitooligosaccharides (MCOs) in a continuous process. The kinetic aspects of immobilized chitosanase (IMMCTase) were investigated based on the reaction time, production of MCOs, and MALDI-TOF mass analyses to achieve maximum bioconversion of high molecular weight chitosan (HMWC) to MCOs. IMMCTase revealed a negligible loss of chitosanase activity after multi uses in continuous digestion of HMWC. The optimal temperature of IMMCTase was 37 °C, and kinetic parameters toward HMWC were determined to be K_m = 1.45 mM and V_max = 360 μmole/μg/min, respectively. Under optimal conditions, the recovery of enzyme activity of IMMCTase was determined to be 82.3%, thus indicating that it can still be reused few more times. In conclusion, use of IMMCTase resulted in rapid and efficient digestions of HMWC with consistent results to produce MCOs.     

Soluble receptor for advanced glycation end products as a potential biomarker to predict weight loss and improvement of insulin sensitivity by a very low calorie diet of obese human subjects

IntroductionObesity is associated with low-grade systemic inflammation which is thought to trigger the development of comorbidities such as type 2 diabetes. The soluble receptor for advanced glycation end products (sRAGE) belongs to the innate immune system and has been linked to obesity, recently. The aim of the present study was to examine whether serum sRAGE concentrations are related to the grade of weight loss and improvement of insulin resistance due to a very low calorie diet (VLCD).Methods22 severe obese subjects (Median Body Mass Index (BMI): 44.5 kg/m²) were included in a dietary intervention study of 6 month, consisting of a very low calorie formula diet phase (VLCD: 800 kcal/d) for 12 weeks and a following 12 week weight maintenance phase. Fasting glucose, fasting insulin, adiponectin, leptin and sRAGE were determined from sera. Insulin sensitivity was estimated by Homeostasis Model Assessment (HOMA) index and leptin-to-adiponectin-ratio (LAR).ResultsMean body weight reduction by VLCD accounted to 21.7 kg with a significant improvement of insulin resistance. At baseline, sRAGE serum levels were significantly inversely related to BMI (r_S = −0.642, p = 0.001) and HOMA (r_S = −0.419, p = 0.041). Of interest, sRAGE serum levels at baseline were significantly lower in study subjects with greater reduction of BMI (p = 0.017). In addition, a significantly greater HOMA reduction was observed in subjects with lower sRAGE serum levels at baseline (p = 0.006). Finally, correlation analysis revealed, that changes of sRAGE serum levels were significantly correlated to changes of BMI (r_S = −0.650, p = 0.022) during intervention.ConclusionAnti-inflammatory sRAGE might be a potential future biomarker to predict weight loss and improvement of insulin resistance by a VLCD whereby lower baseline sRAGE serum levels indicate a better outcome of the dietary intervention.