Chitosan nanofibrous scaffold with graded and controlled release of ciprofloxacin and BMP-2 nanoparticles for the conception of bone regeneration.

The repair of bone defects using grafts is commonly employed in clinical practice. However, the risk of infection poses a significant concern. Tissue engineering scaffolds with antibacterial functionalities offer a better approach for bone tissue repair. In this work, firstly, two kinds of nanoparticles were prepared using chitosan to complex with ciprofloxacin and BMP-2, respectively. The ciprofloxacin complex nanoparticles improved the dissolution efficiency of ciprofloxacin achieving a potent antibacterial effect and cumulative release reached 95 % in 7 h. For BMP-2 complexed nanoparticles, the release time points can be programmed at 80 h, 100 h or 180 h by regulating the number of coating chitosan layers. Secondly, a functional scaffold was prepared by combining the two nanoparticles with chitosan nanofibers. The microscopic nanofiber structure of the scaffold with 27.28 m2/g specific surface area promotes cell adhesion, high porosity provides space for cell growth, and facilitates drug loading and release. The multifunctional scaffold exhibits programmed release function, and has obvious antibacterial effect at the initial stage of implantation, and releases BMP-2 to promote osteogenic differentiation of mesenchymal stem cells after the antibacterial effect ends. The scaffold is expected to be applied in clinical bone repair and graft infection prevention.

Comparative secretome metabolic dysregulation by six engineered dietary nanoparticles (EDNs) on the simulated gut microbiota.

The potential use of engineered dietary nanoparticles (EDNs) in diet has been increasing and poses a risk of exposure. The effect of EDNs on gut bacterial metabolism remains largely unknown. In this study, liquid chromatography-mass spectrometry (LC-MS) based metabolomics was used to reveal significantly altered metabolites and metabolic pathways in the secretome of simulated gut microbiome exposed to six different types of EDNs (Chitosan, cellulose nanocrystals (CNC), cellulose nanofibrils (CNF) and polylactic-co-glycolic acid (PLGA); two inorganic EDNs including TiO2 and SiO2) at two dietary doses. We demonstrated that all six EDNs can alter the composition in the secretome with distinct patterns. Chitosan, followed by PLGA and SiO2, has shown the highest potency in inducing the secretome change with major pathways in tryptophan and indole metabolism, bile acid metabolism, tyrosine and phenol metabolism. Metabolomic alterations with clear dose response were observed in most EDNs. Overall, phenylalanine has been shown as the most sensitive metabolites, followed by bile acids such as chenodeoxycholic acid and cholic acid. Those metabolites might be served as the representative metabolites for the EDNs-gut bacteria interaction. Collectively, our studies have demonstrated the sensitivity and feasibility of using metabolomic signatures to understand and predict EDNs-gut microbiome interaction.

Effects of ingested nanocellulose and nanochitosan materials on carbohydrate digestion and absorption in an in vitro small intestinal epithelium model.

Nanoscale materials derived from natural biopolymers like cellulose and chitosan have many potentially useful agri-food and oral drug delivery applications. Because of their large and potentially bioactive surface areas and other unique physico-chemical properties, it is essential when evaluating their toxicological impact to assess potential effects on the digestion and absorption of co-ingested nutrients. Here, the effects of cellulose nanofibers (CNF), cellulose nanocrystals (CNC), and chitosan nanoparticles (Chnp) on the digestion and absorption of carbohydrates were studied. Starch digestion was assessed by measuring maltose released during simulated digestion of starch solutions. Glucose absorption was assessed by measuring translocation from the resulting digestas across an in vitro transwell tri-culture model of the small intestinal epithelium and calculating the area under the curve increase in absorbed glucose, analogous to the glycemic index. At 1% w/w, CNF and Chnp had small but significant effects (11% decrease and 14% increase, respectively) and CNC had no effect on starch hydrolysis during simulated digestion of a 1% w/w rice starch solution. In addition, at 2% w/w CNC had no effect on amylolysis in 1% solutions of either rice, corn, or wheat starch. Similarly, absorption of glucose from digestas of starch solutions (i.e., from maltose), was unaffected by 1% w/w CNF or CNC, but was slightly increased (10%, p<0.05) by 1% Chnp, possibly due to the slightly higher maltose concentration in the Chnp-containing digestas. In contrast, all of the test materials caused sharp increases (~1.2, 1.5, and 1.6 fold for CNC, CNF, and Chnp, respectively) in absorption of glucose from starch-free digestas spiked with free glucose at a concentration corresponding to complete hydrolysis of 1% w/w starch. The potential for ingested cellulose and chitosan nanomaterials to increase glucose absorption could have important health implications. Further studies are needed to elucidate the mechanisms underlying the observed increases and to evaluate the potential glycemic effects in an intact in vivo system.

Developing Nano-Delivery Systems for Agriculture and Food Applications with Nature-Derived Polymers.

The applications of nanotechnology are wide ranging, and developing functional nanomaterials for agri-food applications from nature-derived polymers is widely conceived as a sustainable approach that is safer for human and animal consumption. In light of this, this review focuses on the advances in the development of nano-delivery systems using nature-derived polymers for agri-food applications. The review opens with a section detailing the different types of nature-derived polymers currently being used in various applications in the agri-food industry with a special mention on microbial extracellular polymeric materials. The major applications of nano-delivery systems in the food sector, such as food fortification and food preservation, as well as in the agricultural sector for controlled release of agrochemicals using nature-derived polymers are discussed. The review ends with a perspective on the safety and public perception of nano-enabled foods with a concluding remark on future directions of incorporating nano-delivery systems for agri-food purposes.

Physicochemical and Morphological Transformations of Chitosan Nanoparticles across the Gastrointestinal Tract and Cellular Toxicity in an In Vitro Model of the Small Intestinal Epithelium.

Nanoscale chitosan materials exhibit size-specific properties that make them useful in agri-food and biomedical applications. Chitosan nanoparticles (Chnps) are being explored as nanocarrier platforms to increase oral bioavailability of drugs and nutraceuticals, but little is known of their fate and transformations in the gastrointestinal tract (GIT) or of their potential toxicity. Here, the GIT fate and cytotoxicity of Chnps, soluble starch-coated Chnps (SS-Chnps), and bulk chitosan powder (Chp), were assessed using a 3-phase simulated digestion and an in vitro cellular small intestinal epithelium model. Physico-chemical characterization revealed dissolution of Chp, but not of Chnps or SS-Chnps, during the gastric phase of digestion, stability of the starch coating of SS-Chnps in the oral and gastric phases, and agglomeration of all materials during the small intestinal phase. A slight but significant (10%, p < 0.01) increase in cytotoxicity (LDH release) was observed with exposure to digested Chnps but not Chp or SS-Chnps.

Small-Intestine-Specific Delivery of Antidiabetic Extracts from Withania coagulans Using Polysaccharide-Based Enteric-Coated Nanoparticles.

Withania coagulans is an Indian medicinal herb, the natural extracts of which are purported to have health-benefiting properties. In this study, the extract was encapsulated in nature-derived polymers with the aim of enhancing its bioavailability. The aqueous extract obtained from the plant W. coagulans was found to elicit the glucose-lowering effect by means of promoting insulin secretion from pancreatic ß cells. The cells treated with the extract showed a nearly 2-fold increase in insulin secretion compared to untreated cells. A delivery system for the extract was developed based on electrosprayed chitosan nanoparticles coated with food-based starch. The enteric starch coating retarded (by 2.5 times) the release of the extract in the stomach. The bioactivity of the encapsulated extract was subsequently tested in vitro on mouse-derived pancreatic ß cells, whereby the delivery system was found to promote insulin secretion. Finally, the extract-encapsulated oral delivery system was tested on diabetic mice and was validated to decrease blood glucose levels by 60%. In summary, it could be inferred that food-grade enteric-coated polysaccharide-based particles increase the bioavailability of the extracted compounds from the plant W. coagulans.

Targeted Gastrointestinal Delivery of Nutraceuticals with Polysaccharide-Based Coatings.

Oral delivery is one of the facile methods for the administration of active ingredients (AIs) like nutraceuticals and drugs. However, its intrinsic disadvantages include poor absorption and bioavailability, degradation of the AI during transit through the gastrointestinal tract (GIT), and a lack of action specificity. Hence, a delivery system for targeted gastrointestinal delivery of AI using polysaccharide-based polymers, that are generally recognized as safe and approved for use as a direct food additive, is proposed. In this regard, mucoadhesive chitosan nanoparticles that could adhere to the mucosa of the GIT are fabricated and encapsulated with AI. These particles are subsequently coated with polysaccharides that have different enzymatic susceptibilities, to allow for specific degradation in the small or large intestines. It is observed that the polysaccharide coating efficiently retarded the nonspecific release of the encapsulated agent until it is exposed to its intended environment of release. The cytotoxicity and uptake of chitosan nanoparticles is further evaluated on Caco2 cells. In conclusion, these polysaccharide-coated nanoparticles can potentially be targeted to different organs in the GIT and to be taken up by the enterocytes for improved oral bioavailability.

Recent advances in complementary and replacement therapy with nutraceuticals in combating gastrointestinal illnesses.

The digestive system provides nourishment to the whole body. Disorders in this system would result in many associated illnesses as the body is deprived of essential nutrients. Gastrointestinal diseases, in particular, gastric ulceration, inflammatory bowel diseases and colorectal cancer have become more prevalent in all population age groups. While this can be attributed to diet and lifestyle changes, the measures to combat these illnesses with conventional drugs is losing popularity owing to the harsh side effects, drug resistance and lack of patient compliance. The focus of this review is to endorse promising nutraceutical dietary components such as phytosterols, polyphenols, anthocyanins and polyunsaturated fatty acids and their synergistic value, in combination with conventional management of key gastrointestinal diseases. As most of these nutraceuticals are labile compounds, the need for protection and delivery using a carrier system is stressed and the methods for targeting to specific parts of the gastrointestinal tract are discussed. A section has also been devoted to perspectives on co-encapsulation methods of drugs and nutraceuticals using different particle systems. Multilayered carrier systems like double layered and core shell particles have been proposed as an exemplary system to co-encapsulate both drugs and nutrients while keeping them segregated.

Advances in stimuli responsive nanobiomaterials for cancer therapy.

Cancer has become one of the major reasons for disease mortality with drastic increase of death rate in recent years. The reason for most of these deaths is due to the inefficacy and failure of the current methods of treatments or due to the unavailability of treatment options. Even after extensive research that has been carried out in the field, there is no gold standard in cancer therapy. With the advancement of the field of nanomedicine and materials science, many research works are being aimed at developing micro and nanocarriers for site-specific delivery of anticancer drugs. As a further advancement in the field, smart carriers, based on nanobiomaterials, which respond to various external and internal stimuli and act locally are being developed to improve the efficacy of current treatments. These smart nanobiomaterials act as carriers for not only anticancer drugs but also for gene and other biomolecules. Keeping the importance and advancement of smart carrier anticancer drug delivery system (AcDDS) in view, this review focuses on stimuli responsive nanobiomaterials that are currently being studied for cancer therapy.

Gradient nanofiber scaffolds for tissue engineering.

Scaffolds are one of the key factors for the success of tissue engineering, in particular when dealing with anchorage-dependent cells. The concept of using scaffolds in tissue engineering lies in mimicking the physical, chemical and biological features of native extracellular matrix (ECM) in order to support cell function, which in turn regulates cellular microenvironment that directs cell growth and subsequent tissue formation. Nanofibers fabricated from both synthetic and natural polymers are being used as scaffolds in many tissue engineering applications. At the molecular level, native ECM is made up of a gradient of fibrous proteins and polysaccharides that are nanoscale structures. The gradient cues of ECM, directs critical cell behaviors such as alignment, motility and differentiation, particularly in the region between soft and hard tissues called interfacial tissue. Therefore, it is essential to develop gradient nanofiber scaffolds particularly for interfacial tissue engineering applications. Keeping these points in view, in this article, we review the recent developments of gradient nanofiber scaffolds, their design strategies, and their applications in tissue engineering.