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The Synthesis and Evaluation of RGD-Conjugated Chitosan Gel as Daily Supplement for Body Weight Control.

ABSTRACT: (1) Background: Obesity is one of the most widespread chronic diseases and increases the risk of several other chronic diseases, especially type 2 diabetes. (2) Methods: Endobarrier is a new medical device what is worn in the small intestines for the treatment of type 2 diabetes and obesity. However, given the invasive and other adverse effects of the Endobarrier, we propose the use of RGD peptide conjugated with chitosan (RC) as an alternative. (3) Results: The FTIR and NMR spectrum showed RGD peptide was successfully conjugated on chitosan and RGD-CT is retained in the small intestine even after digestion. In vitro of wst-1 and live and dead staining studies show that the RGD-CT gel is highly biocompatible and non-toxic. Rats treated with the RGD-CT gel for a short term showed significant decrease change more than 30% in body weight, while the blood and hematic biometrics were within normal values. (4) Conclusions: The RGD-CT gel is safe, suitable for the short-term, reducing visceral fat rate health food to control weight. In the future, it is expected to develop a safe, long-term effective, flexibility of use and low-side-effect anti-obesity therapy in the era of precision medicine by further modification.

SUBMITTER: Chen WY

PROVIDER: S-EPMC8399670 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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The Synthesis and Evaluation of RGD-Conjugated Chitosan Gel as Daily Supplement for Body Weight Control.

Chen Wei-Yao WY Chen Yu-Ting YT Ke Cherng-Jyh CJ Chen Ching-Yun CY Lin Feng-Huei FH

Materials (Basel, Switzerland) 20210810 16

(1) Background: Obesity is one of the most widespread chronic diseases and increases the risk of several other chronic diseases, especially type 2 diabetes. (2) Methods: Endobarrier is a new medical device what is worn in the small intestines for the treatment of type 2 diabetes and obesity. However, given the invasive and other adverse effects of the Endobarrier, we propose the use of RGD peptide conjugated with chitosan (RC) as an alternative. (3) Results: The FTIR and NMR spectrum showed RGD ...[more]

PMID: 34442998

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Project description:Background/objectivesHumans carrying the genetic risk variant C at the circadian CLOCK (Circadian Locomotor Output Cycles Kaput) 3111T/C have been shown to have more difficulties to achieve desired weight loss than TT carriers. We tested the hypothesis that the daily rhythm of autonomic nervous function differs in CLOCK 3111C carriers, leading to reduced effectiveness in weight control.Subjects/methodsWe recruited 40 overweight/obese Caucasian women (body mass index>25), 20 carrying CLOCK 3111C (CC and TC) and 20 non-carriers with matched age and body mass index who participated in a dietary obesity treatment program of up to 30 weeks. Following the treatment, ambulatory electrocardiography was continuously monitored for up to 3.5 days when subjects underwent their normal daily activities. To assess autonomic function, heart rate variability analysis (HRV) was performed hourly to obtain mean inter-beat interval between two consecutive R waves (mean RR) and s.d. of normal-to-normal heartbeat intervals (SDNN), and two parasympathetic measures, namely, proportion of differences between adjacent NN intervals that are >50 ms (pNN50), and high-frequency (HF: 0.15-0.4 Hz) power.ResultsIn the TT carriers, all tested HRV indices showed significant daily rhythms (all P-values <0.0001) with lower mean RR, SDNN, pNN50, and HF during the daytime as compared with the nighttime. The amplitudes of these rhythms except for SDNN were reduced significantly in the C carriers (mean RR: ~19.7%, P=0.001; pNN50: 58.1%, P=0.001; and HF: 41.1%, P=0.001). In addition, subjects with less weight loss during the treatment program had smaller amplitudes in the rhythms of mean RR (P<0.0001), pNN50 (P=0.007) and HF (P=0.003). Furthermore, the rhythmicity-weight loss associations were much stronger in the C carriers as compared to the TT carriers (mean RR: P=0.028, pNN50: P=0.0002; HF: P=0.015).ConclusionsThe daily rhythm of parasympathetic modulation may play a role in the influence of the CLOCK variation on body weight control.

Project description:BackgroundMultidrug resistance (MDR) is the major reason for the failure of chemotherapy in colon cancer. Bufalin (BU) is one of the most effective antitumor active constituents in Chansu. Our previous study found that BU can effectively reverse P-glycoprotein (P-gp)-mediated MDR in colon cancer. However, the clinical application of BU is limited due to its low solubility in water and high toxicity. In the present study, a multifunctional delivery system based on vitamin-E- succinate grafted chitosan oligosaccharide (VES-CSO) and cyclic (arginine-glycine-aspartic acid peptide) (RGD)-modified d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by emulsion solvent evaporation method for targeted delivery of BU to improve the efficacy of drug-resistant colon cancer therapy.MethodsThe cytotoxicity of BU-loaded micelles against drug-resistant colon cancer LoVo/ADR and HCT116/LOHP cells was measured by CCK-8 assay. The cellular uptake, Rho123 accumulation, and cell apoptosis were determined by flow cytometry. The expression of apoptosis-related protein and P-gp was measured by Western blot assay. The antitumor activity of BU-loaded micelles was evaluated in LoVo/ADR-bearing nude mice.ResultsBU-loaded VES-CSO/TPGS-RGD mixed micelles (BU@VeC/T-RGD MM) were 140.3 nm in diameter with zeta potential of 8.66 mV. The BU@VeC/T-RGD MM exhibited good stability, sustained-release pattern, higher intracellular uptake, and greater cytotoxicity in LoVo/ADR cells. Furthermore, the mechanisms of the BU@VeC/T-RGD MM to overcome MDR might be due to enhanced apoptosis rate and P-gp efflux inhibition. Subsequently, in vivo studies confirmed an enhanced therapeutic efficiency and reduced side effects associated with BU@VeC/T-RGD MM compared with free BU, owing to the enhanced permeation and retention effect, improved pharmacokinetic behavior, and tumor targeting, which lead to MDR-inhibiting effect in LoVo/ADR-bearing nude mice.ConclusionOur results demonstrated that VeC/T-RGD MM could be developed as a potential delivery system for BU to improve its antitumor activity against drug-resistant colon cancer.

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Project description:Targeting gut microbiota with synbiotics (probiotic supplements containing prebiotic components) is emerging as a promising intervention in the comprehensive nutritional approach to reducing obesity. Weight loss resulting from low-carbohydrate high-protein diets can be significant but has also been linked to potentially negative health effects due to increased bacterial fermentation of undigested protein within the colon and subsequent changes in gut microbiota composition. Correcting obesity-induced disruption of gut microbiota with synbiotics can be more effective than supplementation with probiotics alone because prebiotic components of synbiotics support the growth and survival of positive bacteria therein. The purpose of this placebo-controlled intervention clinical trial was to evaluate the effects of a synbiotic supplement on the composition, richness and diversity of gut microbiota and associations of microbial species with body composition parameters and biomarkers of obesity in human subjects participating in a weight loss program. The probiotic component of the synbiotic used in the study contained Lactobacillus acidophilus, Bifidobacterium lactis, Bifidobacteriumlongum, and Bifidobacterium bifidum and the prebiotic component was a galactooligosaccharide mixture. The results showed no statistically significant differences in body composition (body mass, BMI, body fat mass, body fat percentage, body lean mass, and bone mineral content) between the placebo and synbiotic groups at the end of the clinical trial (3-month intervention, 20 human subjects participating in weight loss intervention based on a low-carbohydrate, high-protein, reduced energy diet). Synbiotic supplementation increased the abundance of gut bacteria associated with positive health effects, especially Bifidobacterium and Lactobacillus, and it also appeared to increase the gut microbiota richness. A decreasing trend in the gut microbiota diversity in the placebo and synbiotic groups was observed at the end of trial, which may imply the effect of the high-protein low-carbohydrate diet used in the weight loss program. Regression analysis performed to correlate abundance of species following supplementation with body composition parameters and biomarkers of obesity found an association between a decrease over time in blood glucose and an increase in Lactobacillus abundance, particularly in the synbiotic group. However, the decrease over time in body mass, BMI, waist circumstance, and body fat mass was associated with a decrease in Bifidobacterium abundance. The results obtained support the conclusion that synbiotic supplement used in this clinical trial modulates human gut microbiota by increasing abundance of potentially beneficial microbial species.

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The Synthesis and Evaluation of RGD-Conjugated Chitosan Gel as Daily Supplement for Body Weight Control.

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The Synthesis and Evaluation of RGD-Conjugated Chitosan Gel as Daily Supplement for Body Weight Control.

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