Rutin-loaded chitosan nanoparticles alleviated Freund's adjuvant induced rheumatoid arthritis via modulating oxidative stress and inflammatory parameters in Wistar rats.

Rheumatoid arthritis (RA) is the most common chronic inflammatory disease, primarily affecting the joints and with stromal tissue dysregulation causing chronic inflammation and joint destruction. Rutin is a natural flavonoid with potential therapeutic properties in chronic destructive conditions including rheumatoid diseases. In this study, the protective effects of rutin nanoformulation in an animal model of rheumatoid arthritis caused by Freund's complete adjuvant (FCA) were investigated. Sixty male rats were randomly divided into ten groups including normal, negative control, prednisolone 10 mg/kg (positive control), 3 doses of rutin (15, 30, 45mg/kg), rutin nanoparticles (15, 30, 45 mg/kg), and nanoparticle without rutin, for 28 days. Different behavioral parameters including the open field test, acetone drop test, hot plate test, Von Frey test, and inclined plane test were evaluated. Serum levels of glutathione (GSH), catalase, and nitric oxide as well as histopathological analyses were measured in different groups. Also, matrix metalloproteinase (MMP)-2 and MMP-9 activity were appraised by gelatin zymography. The injection of FCA prolonged the rats' immobility duration in comparison to the control group. Rheumatoid arthritis induction also increased nitric oxide and decreased GSH and catalase levels, while these effects were reversed in the groups that received nanoparticles containing rutin and prednisolone. Rutin nanoparticles suppressed MMP-9 and activated MMP-2. Also, this rutin drug delivery system plays a significant role in the improvement of histopathological symptoms. Considering the improvement of behavioral and tissue symptoms and the modulation of the level of inflammatory cytokines, nanoparticles containing rutin can be proposed as a suitable approach in the management of patients with rheumatoid arthritis.

Fabrication of 3D oriented carbon nanofiber by two-nuzzle electrospinning as a cell scaffold.

One of the important issues in tissue engineering has been the development of 3D scaffolds, which guide cells to grow functional tissues and allow the diffusion of nutrients, metabolites, and soluble factors. Factors governing scaffold design include considerations of pore size and morphology, mechanical properties versus porosity, surface properties, and appropriate biodegradability. Three-dimensional structures with low density, high surface area and porosity can be utilized effectively in the tissue engineering. Recently two-nozzle electrospinning was used for fabricate polymeric and ceramic bulky layers with specific formulation. Fabrication of 3D carbon nanofiber with this method was investigated in this assay with FESEM, TGA-DTA, FTIR and XRD. Polyacrylonitrile was used as precursor. The collector speed was changed (15, 30, 60, 150, 300 and 450 rpm) to result in oriented 3D carbon nanofiber after stepwise thermal process under neutral gas atmosphere. The effect of the mechanical force applied by the collector rotation not only can arranged carbon fiber mat but also can change the crystallinity of the carbon structure. The viability and growth capability of cells on nanofibers towards the lowest cytotoxicity of them proved by MTT test. The growth characteristic of neural and mouse bone marrow mesenchymal stem cells cultured in the webs showed the good adhesion with the blown web relative to a normal electrospun mat. The electrospun nanofibers mat had good tensile properties and high porosity and provides a favorable environment for neural cell attachment and proliferation comparable to other scaffolds. The cell viability and cell growth capability in prepared nanofibers were assessed.

Controlled release of 5-fluorouracil to melanoma cells using a hydrogel/micelle composites based on deoxycholic acid and carboxymethyl chitosan.

5-Fluorouracil (5-FU) is an antimetabolite drug widely used for the treatment of skin cancer. Despite its proven efficacy in treating malignancies, its systemic administration is limited due to severe side effects. To address this issue, topical delivery of 5-FU has been proposed as an alternative approach for the treatment of skin cancer, however, the poor permeability of 5-FU through the skin is still a challenge. Here, we introduced a pH-responsive micellar hydrogel system based on deoxycholic acid micelle (DCA Mic) and carboxymethyl chitosan hydrogel (CMC Hyd) to enhance 5-FU efficacy against skin cancer and reduce its systemic side effects by improving its delivery into the skin. The properties of the Mic/Hyd system were determined by Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), zeta sizer, atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Drug release studies showed pH-dependent properties of the Hyd. The final formulation was demonstrated to have enhanced anticancer activity than 5-FU against the growth of melanoma cells. The 5-FU@Mic-Hyd could be a promising delivery platform with enhanced efficacy in the management of skin cancer without systemic toxicity.

Preparation of liposomal hydrogel containing Calendula and application as a wound dressing.

Burn wound is one of the major medical and Hydrogels are one of the best wound dressings for burns. Herein, chitosan/Aloe vera hydrogel was prepared and cross-linked by genipin. The nano-liposomes of soy lecithin as a phospholipid containing calendula were added to the hydrogel. The surface morphology and functional groups were evaluated by SEM and FTIR methods, respectively. The average hydrodynamic diameter was calculated by the dynamic light scattering. Also, the nanoliposomes hydrogel containing calendula has a suitable swelling and vapor permeability. The encapsulation rate of calendula was 83 % which indicates a high load of calendula. In vivo release study of hydrogel containing calendula was achieved by the French diffusion cell. Finally, the cytotoxicity (MTT) test, the proliferation and viability of fibroblast cells (L929) were investigated and the results show no cytotoxicity of the hydrogel. for in vitro study, the passage of calendula-containing liposomes through the skin was investigated. Rat abdominal skin was used as a natural membrane. France diffusion cell was used as a two-compartment model to measure the amount of passage. The skin absorption of the calendula begins with a gentle slope and in 24 h approximately 90% of skin absorption has taken place.

The electrochemical immunosensor for detection of prostatic specific antigen using quince seed mucilage-GNPs-SNPs as a green composite.

Prostatic specific antigen (PSA) is known as a biomarker of prostate cancer. In males, prostate cancer is ranked second as leading cause of death out of more than 200 different cancer types1. As a result, early detection of cancer can cause a significant reduction in mortality. PSA concentration directly is related to prostate cancer, so normal serum concentrations in healthy means are 4 ng and above 10 ng as abnormal concentration. Therefore, PSA determination is important to cancer progression. In this study, a free label electrochemical immunosensor was prepared based on a new green platform for the quantitative detection of the PSA. The used platform was formed from quince seed mucilage containing green gold and silver nanoparticles and synthesized by the green method (using Calendula officinalis L. extract). The quince mucilage biopolymer was used as a sub layer to assemble nanoparticles and increase the electrochemical performance. This nanocomposite was used to increase the antibody loading and accelerate the electron transfer, which can increase the biosensor sensitivity. The antibodies of the PSA biomarker were successfully incubated on the green platform. Under the optimal conditions, the electrochemical impedance spectroscopy (EIS) was proportional to the PSA biomarker concentration from 0.1 pg mL-1 to 100 ng mL-1 with low limit of detection (0.078 pg mL-1). The proposed green immunosensor exhibited high stability and reproducibility, which can be used for the quantitative assay of the PSA biomarker in clinical analyses. The results of real sample analysis presented another tool for the PSA biomarker detection in physiologic models.

Fabrication and characterization of hydrocortisone loaded Dextran-Poly Lactic-co-Glycolic acid micelle.

A nanomicelle based drug delivery systems is a formulation that can improve the bioavailability and dissolution rate of water-insoluble drugs. In this study, the Dextran-Poly Lactic-co-Glycolic Acid copolymer was synthesized with esterification reaction, confirmed using the fourier-transform infrared spectroscopy and nuclear magnetic resonance. The used method for nanomicelle preparation was nanoprecipitation and the critical micelle concentration value was obtained 10 µg/mL. The particle size of the nanomicelle was less than 100 nm ± 4 nm with narrow size distribution (Polydispersity index = 0.06). Hydrocortisone was loaded to this system. The obtained results for the encapsulation efficiency were 79%, and the drug release was adjusted to a first-order kinetic model with 90% release of drug within the 12 h. The MTT assay showed that even in the high concentration of micelle, the cell viability was remained higher than 90%. Considering the toxicity investigation findings, the Dextran-Poly Lactic-co-Glycolic Acid micellar systems can be suggested as a considerable drug delivery system in hydrocortisone pharmaceutical dosage forms.

The application of nanomaterial science in the formulation a novel antibiotic: Assessment of the antifungal properties of mucoadhesive clotrimazole loaded nanofiber versus vaginal films.

Candidiasis is the origin of several chronic diseases and causes a wide range of symptoms from mucosal to systemic and deadly infections. Vaginal patches are one of the best drug delivery systems for the treatment of fungal infections in the vaginal environment, so a mucoadhesive film containing drugs such as clotrimazole and metronidazole is commercially available for patients. In the present study, a physicochemical comparison is made between clotrimazole loaded film and nanofiber fabricated with the new hybrid mucoadhesive formulation of dextran and alginate. Toxicity testing was performed using the MTT assay. Bioadhesion and antifungal effects were investigated for fibers and films. The release behavior of clotrimazole from two systems was evaluated by Franz cell in each case. The most important difference between nanofibrous and film mats were obtained in antifungal, mucoadhesive, Young's modulus and morphology. The nanofiber has a higher antifungal effect and two-fold adhesive to the mouse tissue, than film. The inherent flexibility of nanofiber obviated the need for a plasticizer, which may have cytotoxic side effects. The Clotrimazole loaded nanofibrous of Alginate/Dextran mats were successfully electrospun. They exhibited more bioadhesive with higher and faster antifungal properties versus similar formulation film. Further in vivo investigation is required for their application in vaginal candidiasis.

Efficacy and safety of Achillea wilhelmsii C. Koch capsules on symptom severity and quality of life in patients with irritable bowel syndrome: a randomized, placebo-controlled clinical trial.

Background Irritable bowel syndrome (IBS) is one of the most common digestive diseases. The aim of this clinical trial was to determine the effectiveness of Achillea wilhelmsii C. Koch on the symptom severity and quality of life (QOL) in patients with IBS. Methods The patients were randomized into two groups of 45 each. The QOL and symptom severity of the patients were evaluated at baseline and at completion of the treatments by means of IBS-QOL and IBS severity index. Results The mean severity of clinical symptoms in the Achillea wilhelmsii C. Koch receiving groups before and after the treatment was 282.56 ± 103.57 and 178.06 ± 88.40, and in the placebo group was 265.93 ± 93.56 and 197.74 ± 106.26, respectively. The mean QOL in the Achillea wilhelmsii C. Koch receiving group before and after treatment was 51.49 ± 11.98 and 50.44 ± 13.39 and in the placebo group was 60.71 ± 11.97 and 58.39 ± 11.67, respectively. In both groups, there was a significant difference in the recovery rate in each group (p<0.05). However, the mean difference between the two groups before and after intervention was not significantly different (p>0.05). Also, no patient reported any adverse events during the trial. Although the symptom severity and QOL in both groups were improved compared to those before intervention, there was no significant difference between the two groups. Conclusion It is recommended to conduct future studies with larger sample size and longer treatment periods, and also investigate the efficacy on the IBS subtypes, separately.

Fabrication and in-vitro Investigation of Polycaprolactone - (Polyvinyl Alcohol/Collagen) Hybrid Nanofiber as Anti-Inflammatory Guided Tissue Regeneration Membrane.

BACKGROUND: Periodontal disease is the most common oral condition that affects the tissue surrounding the teeth. The oral cavity is colonized by an impressive array of micro-organisms, many of which can colonize the implants such as Guided Tissue Regeneration (GTR) often utilized in recovering procedures that result in inflammation interfering with the bone regeneration. METHODS: In the current study, a nano-hybrid GTR membrane is developed as a heliacal structure scaffold with localized drug delivery function (Ibuprofen) as an anti-inflammatory agent. Polycaprolactone (PCL) and a blend of Polyvinyl alcohol (PVA)/collagen (Col) (50/50) were electrospun by electrospinning. Ibuprofen (Ibu) was loaded once in the PCL context and once in the hydrophilic portion (PVA/Col). RESULTS: The in vitro release behavior was investigated in each case. Chemical and physical properties were studied for each item. Morphology investigation indicated a heliacal structure with the total average diameter of 1266 nm consististing of porous pores with the average diameter of 256nm. CONCLUSION: The membranes indicated proper mechanical properties and appropriate biodegradation rate as a potential GTR membrane. The controlled and sustained release of Ibu was obtained from both PCL and PVA/COL loaded membranes. Kinetic model study indicated the following zero-order and Higuchi models for the optimum case of PCL loaded and PVA/Col Ibu loaded scaffolds respectively.

Efficacy and safety of a standardized extract from Achillea wilhelmsii C. Koch in patients with ulcerative colitis: A randomized double blind placebo-controlled clinical trial.

BACKGROUND: Using Achillea wilhelmsii as a dietary supplement for gastrointestinal disorders is common in Persian traditional medicine. Its anti-inflammatory, anti-spasmodic and antibacterial properties have been proven by different in vitro and in vivo studies, yet it has not been evaluated in a controlled clinical trial. AIM: This study intended to evaluate the efficacy and safety of A. wilhelmsii in patients with mild to moderate active ulcerative colitis in a randomized, double-blinded, placebo-controlled clinical trial. The hydroalcoholic extract of A. wilhelmsii was standardized based on caffeic acid. METHODS: Forty-nine patients were randomly received A. wilhelmsii capsules or placebo, twice daily for 4 weeks in a 1:1 ratio. The disease activity index (DAI) (Partial Mayo Score), haemoglobin, platelet count, erythrocyte sedimentation rate (ESR) and serum level of C-reactive protein (CRP) were measured at the entry and the end of the treatment. To standardize the extract, caffeic acid was detected and measured in the plant extract using high performance liquid chromatography (HPLC). RESULTS: Of 49 patients who entered the trial, 40 patients completed the study. In both treatment and placebo groups, significant reductions were observed in stool frequency, rectal bleeding, physician global assessment and partial mayo score. There was no significant difference in stool frequency (P = 0.176), rectal bleeding (P = 0.523), physician global assessment (P = 0.341) and partial mayo score (P = 1) in the treatment versus the placebo groups. Laboratory variables including hemoglobin, platelet count, ESR and CRP showed no significant difference between the treatment and the placebo group. Of all participants, only one patient in the treatment group complained about skin rash (grade 1 based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0). CONCLUSION: Oral administration of A. wilhelmsii powder for 4 weeks did not create a clinical response more than placebo. It seemed to be safe in UC patients. Further studies are obligatory to evaluate the therapeutic potential of A. wilhelmsii in the form of extract in UC patients.

Biomacromolecular Based Fibers in Nanomedicine: A Combination of Drug Delivery and Tissue Engineering.

BACKGROUND: Biopolymers based materials (polysaccharides, lipids, proteins, and nucleic acids) are one of the basic resources in bio-engineering sciences because of desirable features. Moreover, nanobiotechnology innovates nanomaterial and associated technique in nano medicine (drug delivery and tissue engineering). METHODS: In the nano-medicine, fibers are introduced as a successful biomimetic extracellular matrix scaffolds and drug carrier systems. Electrospinning as a simple and cost-effective technique is used to design nanofibers. Natural polymers including chitosan, alginic acid, hyaluronic acid, collagen, gelatin, and albumin are excellent candidates for electrospinning. However, these types of biopolymers typically have difficulty in electrospinning. RESULTS: Therefore, for spinning of these polymers, the condition of the procedure including solvent, copolymer addition, cross-linker addition, and optimization of spinning should be done. CONCLUSION: The present study gathered information about fiber-based nanodevices from biopolymers in a drug transportation or tissue engineering.