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Objectives Cytokines released by infiltrating T cells may promote mechanisms leading to fibrosis in scleroderma. The aim of this study was to investigate the role of the Th2 cytokine IL-31, and its receptor IL-31RA, in scleroderma skin and lung fibrosis. Methods IL-31 was measured by ELISA of plasma, and by immunochemistry of fibrotic skin and lung tissue of scleroderma patients. The receptor, IL-31RA, was assayed by qPCR of tissue resident cells. Next-generation sequencing was used to profile the responses of normal skin fibroblasts to IL-31. In wild-type Balb/c mice, IL-31 was administered by subcutaneous mini pump, with or without additional TGFβ, and the fibrotic reaction measured by histology and ELISA of plasma. Results IL-31 was present at high levels in plasma and fibrotic skin and lung lesions in a subset of scleroderma patients, and the receptor overexpressed by downstream cells relevant to the disease process, including skin and lung fibroblasts, through loss of epigenetic regulation by miR326. In skin fibroblasts, IL-31 induced next generation sequencing profiles associated with cellular growth and proliferation, anaerobic metabolism and mineralization, and negatively associated with angiogenesis and vascular repair, as well as promoting phenotype changes including migration and collagen protein release via pSTAT3, resembling the activation state in the disease. In mice, IL-31 induced skin and lung fibrosis. No synergy was seen with TGFβ, which supressed IL-31RA. Conclusion IL-31/IL-31RA is confirmed as a candidate pro-fibrotic pathway, which may contribute to skin and lung fibrosis in a subset of scleroderma patients.

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Biodegradable materials are extensively employed to design nanocarriers that mimic extracellular environment in arthritis. The aim of this study was to formulate and characterize biocompatible, biodegradable ketoprofen-loaded chitosan-chondroitin sulfate (CHS-CS) nanoparticles with natural ingredients for transdermal applications. Polymers used in the design of nanocarriers are biodegradable and produce synergistic anti-inflammatory effect for the treatment of arthritis. For transdermal application, argan oil-based emulgel is utilized to impart viscosity to the formulation. Furthermore, naturally occurring argan oil synergizes anti-inflammatory effect of formulation and promotes skin penetration. CHS and CS form nanoparticles by polyelectrolyte complex formation or complex coacervation at pH 5.0. These particles were loaded into argan oil-based emulgel. Employing this method, nanoparticles were formulated with particle size in the range of 300-500 nm. These nanocarriers entrapped ketoprofen and showed more than 76% encapsulation efficiency and 77% release of the ketoprofen at pH 7.4 within 72 h. Drug releases from CHS-CS nanoparticles by mechanism of simple diffusion. Nanoparticle-loaded argan oil emulgel significantly enhanced skin penetration of ketoprofen as compared to marketed gel (p < 0.05). Nanocarriers prepared successfully delivered drug through transdermal route using natural ingredients. Graphical abstract ᅟ.

Nanotechnology has burgeoned over last decade exploring varieties of novel applications in all areas of science and technology. Utilisation of bio-friendly polymers for engineering nanostructures (NS) improves safety and efficacy in drug delivery. Biopolymers not merely employed for fabricating drug carriers but also leveraged for surface functionalisation of other NS to impart bio-mimicking properties. Biopolymer functionalised NS garnered researcher's attention because of their potential to enhance skin permeability of drug cargo. Biopolymers, i.e. cell-penetrating peptides (CPP), chitosan and hyaluronic acid not only enhance skin permeability but also add multiple functions due to their intrinsic biomimetic properties. This multifunctional drug delivery system is a promising tool to achieve skin delivery of large number of therapeutic agents. In this review, functionalisation of NS with biopolymers particularly polysaccharides and polypeptides is discussed in detail. In particular, applications of these functionalised NS for TDDS is elaborated. Moreover, this review provides framework for elaborating importance of functionalisation of NS to enhance skin permeability and depicts advantages of biopolymers to construct more biocompatible carriers for drug cargos.

Cervical carcinoma is one of the most prevalent gynecological cancers throughout the world. Cisplatin is used as first line chemotherapy for treatment of cervical cancer, but it comes with plethora of side effects. The aim of this study was to develop hyaluronic acid coated, thiolated chitosan nanocarriers using green synthesis approach, for CD44 targeted delivery and sustained release of Cisplatin in cervical cancer cells. After synthesis through ionic gelation method, Zeta analysis showed that the nanoparticle size was 265.9 nm with a zeta potential of +22.3 mV and .226 PDI. SEM and TEM analysis confirmed the spherical shape and smooth surface of nanoparticles. FTIR and XRD showed the presence of characteristic functional groups, successful encapsulation of drug, and crystalline nature of nanoparticles respectively. Drug loading and entrapment efficiency were calculated to be 70.1% ± 1.2% and 45% ± .28% respectively. Analysis of in vitro drug release kinetics showed that drug release followed the Higuchi model at pH 6.8 and 7.4 and Cisplatin release for up to 72 h confirmed sustained release. In vitro analysis on cervical cancer cells HeLa and normal cervical epithelial cells HCK1T was done through cell morphology analysis, trypan blue assay (concentration range of 10–80 μg/ml), and MTT cytotoxic assay (concentration range of 10–90 μg/ml). The results showed a higher cytotoxic potential of HA coated, thiolated chitosan encapsulated Cisplatin (HA-ThCs-Cis NP) nanoformulation as compared to pure Cisplatin in HeLa while in HCK1T, pure Cisplatin showed much higher toxicity as compared to HA-ThCs-Cis nanoformulation. These findings suggest that CD44 targeted delivery system can be a useful approach to minimize offtarget toxicities, give sustained release and better cellular uptake in cancer cells.

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In this study, nano-cerium dioxide doped titanium-dioxide (CeO2-TiO2) Nanocomposites (NCs) was used for the photocatalytic degradation of pollutant parameters (color, polyphenols, polyaromatics) from a textile industry wastewater (TI ww) treatment plant located in Izmir, Turkey, at different operational conditions such as at increasing photocatalytic time (0, 10, 15, 20, 30, 60, 90 and 120 min), at different CeO2-TiO2 mass ratios (1%, 3%, 5%, 10%, 15%, 16%, 25%, 30%, 50%), at the different amounts of CeO2 (1, 3, 5, 8, 10, 15, 20 and 25 mg/L) under 130 W Ultraviolet (UV) and 35 W sun lights irradiations, respectively. Color, polyphenols (quercetin, fisetin, ellargic acid, carminic acid, luteolin, and curcumin) and polyaromatics [2,6-dimethylaniline (2,6-DMA), 2-aminoanisole (MOA), 2,4-toluenediamine (TDA), 2-naphthylamine (NA), 4,40-thiobisbenzenamine (TOA), 3,3-dichlorobenzidine (DCB) and 3,30-dimethoxybenzidine (DMOB)] removal efficiencies were observed between 78% and 99% during photocatalytic experiments, under 130 W UV light, at 15% CeO2-TiO2 NCs, at 21°C, after 30 min irradiation time. 15% CeO2-TiO2 NCs shows the highest photodegradation yield of color under both UV and visible-light irradiation, with maximum photo-degradation rates of 99% and 98.5%, respectively, after 30 min irradiation time. 94.44% maximum Microtox acute toxicity yield was found in CeO2-TiO2 NCs = 20 mg/L, at 5% CeO2 mass ratio, after 150 min photodegradation time at 60oC. 90% maximum Daphnia magna acute toxicity removal was obtained in CeO2-TiO2 NCs = 20 mg/L, at 5% CeO2 mass ratio, after 150 min photodegradation time at 60°C. The results show that the CeO2-TiO2 NCs has a high photocatalytic activity to remove the pollutants from TI ww.