ECM-mimetic, NSAIDs loaded thermo-responsive, immunomodulatory hydrogel for rheumatoid arthritis treatment.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches for RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biological agents. To overcome the drug-associated toxicity of conventional therapy and transdermal tissue barrier, an injectable NSAID-loaded hydrogel system was developed and explored its efficacy. RESULTS: The surface morphology and porosity of the hydrogels indicate that they mimic the natural ECM, which is greatly beneficial for tissue healing. Further, NSAIDs, i.e., diclofenac sodium, were loaded into the hydrogel, and the in vitro drug release pattern was found to be burst release for 24 h and subsequently sustainable release of 50% drug up to 10 days. The DPPH assay revealed that the hydrogels have good radical scavenging activity. The biocompatibility study carried out by MTT assay proved good biocompatibility and anti-inflammatory activity of the hydrogels was carried out by gene expression study in RAW 264.7 cells, which indicate the downregulation of several key inflammatory genes such as COX-2, TNF-α & 18s. CONCLUSION: In summary, the proposed ECM-mimetic, thermo-sensitive in situ hydrogels may be utilized for intra-articular inflammation modulation and can be beneficial by reducing the frequency of medication and providing optimum lubrication at intra-articular joints.

Citrus Essential Oils in Aromatherapy: Therapeutic Effects and Mechanisms.

Citrus is one of the main fruit crops cultivated in tropical and subtropical regions worldwide. Approximately half (40-47%) of the fruit mass is inedible and discarded as waste after processing, which causes pollution to the environment. Essential oils (EOs) are aromatic compounds found in significant quantities in oil sacs or oil glands present in the leaves, flowers, and fruit peels (mainly the flavedo part). Citrus EO is a complex mixture of ~400 compounds and has been found to be useful in aromatic infusions for personal health care, perfumes, pharmaceuticals, color enhancers in foods and beverages, and aromatherapy. The citrus EOs possess a pleasant scent, and impart relaxing, calming, mood-uplifting, and cheer-enhancing effects. In aromatherapy, it is applied either in message oils or in diffusion sprays for homes and vehicle sittings. The diffusion creates a fresh feeling and enhances relaxation from stress and anxiety and helps uplifting mood and boosting emotional and physical energy. This review presents a comprehensive outlook on the composition, properties, characterization, and mechanism of action of the citrus EOs in various health-related issues, with a focus on its antioxidant properties.

Bio-sorbents, industrially important chemicals and novel materials from citrus processing waste as a sustainable and renewable bioresource: A review.

Citrus waste includes peels, pulp and membrane residue and seeds, constituting approximately 40-60% of the whole fruit. This amount exceeds ~110-120 million tons annually worldwide. Recent investigations have been focused on developing newer techniques to explore various applications of the chemicals obtained from the citrus wastes. The organic acids obtained from citrus waste can be utilized in developing biodegradable polymers and functional materials for food processing, chemical and pharmaceutical industries. The peel microstructures have been investigated to create bio-inspired materials. The peel residue can be processed to produce fibers and fabrics, 3D printed materials, carbon nanodots for bio-imaging, energy storage materials and nanostructured materials for various applications so as to leave no waste at all. The article reviews recent advances in scientific investigations to produce valuable products from citrus wastes and possibilities of innovating future materials and promote zero remaining waste for a cleaner environment for future generation.

Modern Extraction and Purification Techniques for Obtaining High Purity Food-Grade Bioactive Compounds and Value-Added Co-Products from Citrus Wastes.

Citrus contains a range of highly beneficial bioactive compounds, such as polyphenols, carotenoids, and vitamins that show antimicrobial and antioxidant properties and help in building the body's immune system. On consumption or processing, approximately 50% of the fruit remains as inedible waste, which includes peels, seeds, pulp, and segment residues. This waste still consists of substantial quantities of bioactive compounds that cause environmental pollution and are harmful to the ecosystem because of their high biological oxygen demand. In recent years, citrus cultivation and the production of processed foods have become a major agricultural industry. In addition to being a substantial source of economy, it is an ideal and sustainable and renewable resource for obtaining bioactive compounds and co-products for food and pharmaceutical industries. In the present article, the various methods of extraction, conventional and modern, as well as separation and isolation of individual bioactive compounds from the extraction mixture and their determination have been reviewed. This article presents both aspects of extraction methods, i.e., on a small laboratory scale and on an industrial mass scale. These methods and techniques have been extensively and critically reviewed with anticipated future perspectives towards the maximum utilization of the citrus waste.

Citrus essential oils: Extraction, authentication and application in food preservation.

Citrus EOs is an economic, eco-friendly and natural alternatives to chemical preservatives and other synthetic antioxidants, such as sodium nitrites, nitrates or benzoates, commonly utilized in food preservation. Citrus based EOs is obtained mainly from the peels of citrus fruits which are largely discarded as wastes and cause environmental problems. The extraction of citrus oils from the waste peels not only saves environment but can be used in various applications including food preservation. The present article presents elaborated viewpoints on the nature and chemical composition of different EOs present in main citrus varieties widely grown across the globe; extraction, characterization and authentication techniques/methods of the citrus EOs; and reviews the recent advances in the application of citrus EOs for the preservation of fruits, vegetables, meat, fish and processed food stuffs. The probable reaction mechanism of the EOs based thin films formation with biodegradable polymers is presented. Other formulation, viz., EOs microencapsulation incorporating biodegradable polymers, nanoemulsion coatings, spray applications and antibacterial action mechanism of the active compounds present in the EOs have been elaborated. Extensive research is required on overcoming the challenges regarding allergies and obtaining safer dosage limits. Shift towards greener technologies indicate optimistic future towards safer utilization of citrus based EOs in food preservation.

Drug-eluting balloon: design, technology and clinical aspects.

A drug-eluting balloon is a non-stent technology in which the effective homogenous delivery of anti-proliferative drugs is processed by the vessel wall through an inflated balloon. This is done to restore luminal vascularity in order to treat atherosclerosis, in-stent restenosis and reduce the risk of late thrombosis without implanting a permanent foreign object. The balloon technology relies on the concept of targeted drug delivery, which helps in the rapid healing of the vessel wall and prevents the proliferation of smooth muscle cells. Several drug eluting devices in the form of coated balloons are currently in clinical use, namely DIOR®, PACCOCATH®, SeQuent®Please and IN.PACT™. The device varies in terms of the material used for making the balloon, the coating techniques, the choice of coated drug and the release pattern of the drug at the site. This review gives an insight into the evolution, rationale and comparison of the marketed drug-eluting balloons. Here, different coating techniques have been analysed for the application and critical analysis of available DEB technologies, and a technical comparison has been done.

Design and evaluation of artificial cornea with core-skirt design using polyhydroxyethyl methacrylate and graphite.

PURPOSE: Artificial cornea is the effective treatment option for corneal blindness. One of the challenges with the artificial cornea is limited, or no tissue integration necessitates reimplantation due to necrosis or corneal melting. We propose here a new formulation approach for core-skirt incorporating graphite in the outer skirt region to improve cell adhesion. METHODS: Hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate were procured from Sigma-Aldrich. Polyhydroxyethyl methacrylate (PHEMA) was synthesized by free radical polymerization of HEMA. PHEMA hydrogel core with graphite incorporated skirt was developed with the help of mould and spacer. Pores were introduced into the skirt by salt leaching technique using sodium chloride as porogen. The porous skirt was improved for its aesthetic appeal of black colour and mechanical strength to sustain intraocular pressure by incorporating graphite. The material properties of the newly developed design were evaluated in terms of wetting behaviour, mechanical strength, water vapour permeability, degradation profile and cell adhesion. RESULTS: The polymerization of HEMA was confirmed by thin layer chromatography and FTIR. Water content of the polymeric film was optimized at 50% where maximum transparency with required refractive index of 1.4 was obtained. The concentration of salt vital for the essential porosity was also optimized using optical microscopy and scanning electron microscopy. Other properties, namely mechanical strength, water vapour transmission rate and degradation behaviour, showed that the developed design is suitable for ocular applications. Furthermore, cell adhesion study confirmed tissue adhesion in the skirt region but absent in the core. CONCLUSION: The core-skirt design may offer an efficient cornea replacement alternative with enhanced tissue integration in addition to desired mechanical behaviour with a clear and aesthetic vision.

Nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/collagen/graphene oxide scaffolds for wound coverage.

The purpose of wound management is to prevent wound from infection, increase the fibroblast cell growth, and preserve cellular function. The polymeric electrospun nanofiber scaffold made up of natural and/or synthetic polymer provides an extracellular matrix for support and initiates the growth, proliferation and differentiation of fibroblast cells. The present study deals with the development of poly3-hydroxybutyric acid-co-3-hydroxyvaleric acid (PHBV) nanofibrous scaffold imbedded with graphene oxide (GO), and collagen. Nanofibrous PHBV offers advantages like structural resemblance to native extracellular matrix, high porosity and surface area to volume ratio. The nanofibrous mats were morphologically and chemically characterized by Field Emission Scanning Electron Microscopy (FESEM) and Fourier Transform Infrared (FTIR) Spectroscopy. FESEM images showed the nanofiber diameter was decreased and porosity increased by adding GO and collagen into the matrix without any chemical interaction among them. Incorporation of GO into the matrix increases mechanical strength of scaffold in addition to antibacterial activity against E. coli and S. aureus with decrease in pore size and hydrophilicity. In contrast, collagen addition into the nanofibers enhanced hydrophilicity without affecting mechanical strength and porosity significantly. Moreover, collagen enhanced cell proliferation capacity of nanofibers in comparison to the samples of PHBV+GO and virgin PHBV. The combination of collagen and GO with PHBV has balanced properties which can be utilised for the application.

A review on carrier systems for bone morphogenetic protein-2.

Bone morphogenetic protein-2 (BMP-2) has unique bone regeneration property. The powerful osteoinductive nature makes it considered as second line of therapy in nonunion bone defect. A large number of carriers and delivery systems made up of different materials have been investigated for controlled and sustained release of BMP-2. The delivery systems are in the form of hydrogel, microsphere, nanoparticles, and fibers. The carriers used for the delivery are made up of metals, ceramics, polymers, and composites. Implantation of these protein-loaded carrier leads to cell adhesion, degradation which eventually releases the drug/protein at site specific. But, problems like ectopic growth, lesser protein delivery, inactivation of the protein are reported in the available carrier systems. Therefore, it is need of an hour to modify the available carrier systems as well as explore other biomaterials with desired properties. In this review, all the reported carrier systems made of metals, ceramics, polymers, composites are evaluated in terms of their processing conditions, loading capacity and release pattern of BMP-2. Along with these biomaterials, the attempts of protein modification by adding some functional group to BMP-2 or extracting functional peptides from the protein to achieve the desired effect, is also evaluated. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 904-925, 2017.