Cyclotide nanotubes as a novel potential Drug-Delivery System: Characterization and biocompatibility.

Cyclotides are a class of cyclic peptides that can be self-assembled. This study aimed to discover the properties of cyclotide nanotubes. We performed differential scanning calorimetric (DSC) to characterize their properties. Then, we incorporated the coumarin as a probe and identified the morphology of nanostructures. The stability of cyclotide nanotubes after 3 months of keeping at -20 °C was determined by field emission scanning electron microscopy (FESEM). The cytocompatibility of cyclotide nanotubes was evaluated on peripheral blood mononuclear cells. In vivo, studies were also conducted on female C57BL/6 mice by intraperitoneally administration of nanotubes at 5, 50, and 100 mg/kg doses. Blood sampling was done before and 24 h after nanotube administration and complete blood count tests were conducted. DSC thermogram showed that the cyclotide nanotubes were stable after heating until 200 °C. Fluorescence microscopy images proved that the self-assembled structures of cyclotide can encapsulate the coumarin. FESEM proved that these nanotubes were stable even after 3 months. The results of the cytotoxicity assay and in-vivo study confirmed that these novel prepared nanotubes were biocompatible. These results suggested that the cyclotide nanotubes could be considered as a new carrier in biological fields while they are biocompatible.

Preparation of chitosan nanoparticles for simultaneous drug delivery of dacarbazine and enoxaparin in melanoma.

The aim of this study was to investigate the anti-melanoma and anti-angiogenic effects of enoxaparin surface-coated dacarbazine-loaded chitosan nanoparticles (Enox-Dac-Chi NPs). The prepared Enox-Dac-Chi NPs had a particle size of 367.95 ± 1.84 nm, zeta potential of -7.12 ± 0.25 mV, efficiency of drug loading (DL%) of 73.90 ± 3.84 %, and attached enoxaparin percentage of 98.53 ± 0.96 %. Both drugs had extended-release profiles and approximately 96 % of enoxaparin and 67 % dacarbazine were released within 8 h. The Enox-Dac-Chi NPs with IC50 of 59.60 ± 1.25 µg/ml were the most cytotoxic against melanoma cancer cells compared with chitosan nanoparticles containing only dacarbazine (Dac-Chi NPs) and free dacarbazine. There was no significant difference between the cellular uptake of Chi NPs and enoxaparin coated Chi NPs (Enox-Chi NPs) in B16F10 cells. Enox-Chi NPs with an average anti-angiogenic score of 1.75 ± 0.125 had more anti-angiogenic effect than enoxaparin. The results showed that simultaneous delivery of dacarbazine and enoxaparin by chitosan nanoparticles can enhance the anti-melanoma effect of dacarbazine. Additionally, enoxaparin can prevent the melanoma metastasis by its anti-angiogenic activity. Thus, the designed nanoparticles can be introduced as effective drug delivery vehicles for the treatment and prevention of metastatic melanoma.

Morphological studies of self-assembled cyclotides extracted from Viola odorata as novel versatile platforms in biomedical applications.

Self-assembling peptides have attracted researchers' attention recently. They are classified as biomedical materials with unique properties formed in response to environmental conditions. Cyclotides are macrocyclic plant-derived peptides containing 28-37 amino acids that have the ability to self-assemble. Herein, we investigated the effect of pH, time, and temperature on the self-assembling properties of the cyclotides extracted from Viola odorata. For this purpose, the cyclotides were dispersed in aqueous trifluoroacetic acid at pH 2, 4, or 6 and incubated at 25 or 37 °C for 1, 2, 3, 5, 7 or 10 days, and the morphology of the self-assembled structures was identified by optical microscopy, polarized optical microscopy, scanning electron microscopy, transmission electron microscopy, and fluorescence microscopy. At pH 2 and 4, the self-assembly process of cyclotides comprises a number of steps, starting with the formation of spherical peptide nanostructures followed by hierarchically assembled nanotubes, and then shifting to nanofibers after 10 days. At pH 6, amorphous structures were produced even after 10 days. The temperature also could affect the self-assembly mechanism of the cyclotides. At 25 °C, the spherical peptide micelles formed firstly and then merged to form nanotubes, while at 37 °C the cyclotides showed crystallization followed by an increase in length with time. The fluorescence microscopy images showed that the nanotubes could efficiently entrap the hydrophobic molecules of coumarin. This comparative study on the self-assembly of the cyclotides extracted from Viola odorata is the first example exploring the capacity of these cyclotides to adopt precise nanostructures. The nanotubes and nanofibers obtained with these cyclotides might find interesting applications in drug delivery and tissue engineering.

Immunomodulatory effects of cyclotides isolated from Viola odorata in an experimental autoimmune encephalomyelitis animal model of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that causes chronic inflammation. Cyclotides are small plant proteins with a wide range of biological activity, making them a target for researchers to investigate. This study was conducted to investigate the possible effects of cyclotide-rich fractions from Viola odorata as an immunomodulatory agent in an experimental autoimmune encephalomyelitis (EAE) model of MS. METHODS: At room temperature, the plant materials were subjected to maceration in methanol: dichloromethane (1:1; v/v) for 3 days. The extraction was repeated 3 times, and the final concentrated extract was partitioned 3 times by 1/2 volume of double-distilled water. The aqueous phases were separated and freeze-dried. Finally, the crude extract was fractionated by C18 silicagel using vacuum liquid chromatography, with mobile phases of 30%, 50% and 80% of ethanol: water, respectively. The 50%, and 80% fractions were analyzed by HPLC and MALDI-TOF analysis and administrated intraperitoneally to forty-five female C57BL/6 EAE-induced mice, at 5, 25, and 50 mg/kg doses. After 28 days, the animals were evaluated using EAE clinical scoring which was done every 3 days, cytokine levels, and myelination level. RESULTS: The results confirmed the presence of cyclotides in V. odorata based on their retention time and the composition of mobile phase in HPLC and the molecular weight of the peaks in MALDI-TOF analysis. It was observed that cyclotides, especially in the 80% fraction group at the dose of 50 mg/kg significantly reduced the clinical scores, inflammation, and demyelination in EAE mice compared with the normal saline group (P<0.05), and the results of this group were comparable with fingolimod (P>0.05). CONCLUSION: It could be concluded that V. odorata is a rich source of cyclotides which they could be extracted by an easily available process and also, they could be used as immunomodulatory agents in MS, with similar effects to fingolimod.

The Effect of Topical Cow's Milk on the Healing of Diabetic Foot Ulcers: A Randomized Controlled Pilot Clinical Trial.

Diabetic foot ulcer (DFU) is a very serious side effect among the diabetic patients with substantial clinical and economic consequences. The aim of this study was to investigate the efficacy of cows' milk topical ointment, as an available and cost-effective natural product, on accelerating the healing of DFU. In this randomized controlled clinical trial, patients with grade 1 or 2 DFU were randomly divided into two groups of intervention (n = 50) and control (n = 49). For patients of intervention group, cows' milk 20% topical ointment was applied on the ulcer once daily for two weeks, while a type of novel dressing was used for control group with the same frequency and duration. Both groups received usual standard wound care measures. The percentage of change in the ulcer size and the number of cases with complete wound healing (>90% reduction in the ulcer size) were recorded in the both groups. The ulcer size significantly reduced in both groups on the seventh and 14th days of intervention; however, the percentage of reduction was significantly higher in the intervention (milk) group compared to control at both time points (44.64 ± 15.98 vs. 24.95 ± 12.78, P < .001; 67.67 ± 22.15 vs. 42.87 ± 19.74, P < .001). Furthermore, although more patients in the intervention group (n = 4, 8%) showed complete healing of the ulcer compared to control (n = 0), the difference was not statistically significant (P = .117). Cow's milk 20% topical ointment improves and accelerates the healing of diabetic foot ulcers. However, more clinical studies are required to confirm these effects.

The effectiveness of olibanum orally disintegrating tablet in the treatment of oral aphthous ulcers: A randomized, double-blind, placebo-controlled clinical trial.

Background: Boswellia serrata oleo-gum-resin (frankincense; olibanum) has anti-inflammatory, analgesic, and antimicrobial effects. This study aimed to evaluate the clinical effectiveness of frankincense extract in the treatment of oral aphthous ulcers. Materials and Methods: In a randomized, double-blind, placebo-controlled clinical trial, patients with aphthous ulcers were randomly assigned to either experimental (Frankincense extract) or placebo groups to use orally disintegrating tablets (ODT) of frankincense and placebo, respectively, four times a day for 3 days. The size of aphthous ulcers and the pain severity by visual analogue scale were recorded at days 0, 2, and 4 and compared between the groups. Results: Twenty-five patients in each group completed the study. Olibanum extract ODT significantly reduced the ulcer size on the second (P < 0.001) and fourth (P < 0.001) days as well as the pain score on the second (P = 0.002) and fourth (P < 0.001) days of the intervention compared to placebo. Furthermore, at the end of the intervention, the number of patients with complete ulcer healing and pain relief in the experimental group was significantly more than the placebo group (5 vs. 0, P = 0.02; and 11 vs. 0, P < 0.001, respectively). Conclusion: Taking olibanum extract ODTs reduces the ulcer size and pain severity and accelerates the healing process in the oral aphthous lesions.

3D printed tablets containing oxaliplatin loaded alginate nanoparticles for colon cancer targeted delivery. An in vitro/in vivo study.

This study aimed to develop a colon-targeted tablet of oxaliplatin (OP) using the combination of nanotechnology and fused deposition modeling (FDM) 3D printing to improve its antitumor activity, tumor targetability, and safety profile. Eudragit L100-55 filament containing OP loaded alginate nanoparticles (OP-NPs) were fabricated using hot-melt extrusion method and printed by an FDM printer to 3D printed tablets with good uniformity in the drug content and selective release of OP in the colonic environment. The antitumor effect of 3D printed tablets containing OP-NPs in CT-26 tumor-bearing mice was evaluated compared to intravenous and oral administration of OP solution, and compressed tablets containing OP-NPs, which were prepared by direct compression method with the same formulation. The antitumor effect of 3D printed tablets containing OP-NPs was remarkable and comparable with intravenous OP solution (p Ëƒ 0.05) with a better safety profile, whereas compressed tablets did not show any significant antitumor effect, probably in terms of non-selective drug release in stomach and upper intestine environments. This study highlights the potential of the combination of nanotechnology and 3D printing in the preparation of colon-specific drug delivery systems of chemotherapeutic drugs with good antitumor activity, tumor targetability, and safety profile for colorectal cancer treatment.

Preparation and characterization of 3D printed PLA microneedle arrays for prolonged transdermal drug delivery of estradiol valerate.

Biodegradable polymeric microneedle arrays (BPMNAs) could be explored as potential devices for transdermal drug delivery, which can provide a painless and safe drug delivery method. BPMNAs could also provide high drug-loading capacity and prolonged drug delivery once integrated with a drug reservoir. However, the fabrication of MNAs with a drug reservoir is expensive and requires complicated procedures. The present study was conducted to describe the preparation of a reservoir-based BPMNA containing estradiol valerate using polylactic acid (PLA) with the combination of FDM 3D printing and injection volume filling techniques. The tip size of the 3D printed needles decreased to 173 µm utilizing a chemical etching process. The content of estradiol valerate loaded in the 3D printed PLA MNAs was 29.79 ± 0.03 mg, and the release was in a prolonged manner for up to 7 days. The results of mechanical tests revealed that the force needed for the 3D printed PLA MNAs fracture (900 N) was significantly higher than that needed for their skin penetration (4 N). The successful penetration of 3D printed PLA MNAs through the stratum corneum was confirmed via penetration test, methylene blue staining, and histological examination. The results showed that 3D printed PLA MNAs can penetrate into the skin without reaching to the dermal nerves and puncture of blood vessels. In conclusion, in the current study, we explored the practicability of the preparation of drug loaded reservoir-based BPMNAs using the combination of FDM 3D printing and injection volume filling techniques for painless and prolonged transdermal drug delivery.

Preparation and in vitro evaluation of Vancomycin loaded Montmorillonite-Sodium Alginate topical gel for wound infection

Abstract Despite decades of research, wound healing remains a significant public health problem. This study aimed to develop and evaluate a topical sodium alginate gel containing vancomycin (Van) loaded MMT NPs for wound healing applications. Van was loaded in MMT at different conditions (pHs of 6, 7 and temperatures of 40, 50 °C) (Van/MMT NPs). The optimum formulation (with the smallest particle size and a high value of zeta potential; 270.8 ± 77.35 nm and -35.96 ± 2.73, respectively) showed a high drug-loading capacity (entrapment efficacy of 96%) and a sustained release pattern of Van (95%) over 480 min. The optimum Van/MMT NPs were embedded into the sodium alginate (SA) gel (Van/MMT NPs/SA gel). The Van/ MMT NPs/SA gel showed a sustained and slow release pattern of Van (95%) over 50 h. FTIR tests revealed the electrostatic interaction between MMT and Van. The broth macrodilution tube method was used to determine the minimum inhibitory concentration (MIC) of Van, Van/ MMT NPs, and Van/MMT NPs/SA gel against Staphylococcus aureus. The results showed the promising antibacterial activity of Van/MMT NPs/SA gel, thus, this gel can be a promising formulation for the management of infected wounds

Niosome-carvedilol protects DNA damage of supraphysiologic concentrations of insulin using comet assay: An in vitro study.

Introduction: Hyperinsulinemia occurs in type 2 diabetic patients with insulin resistance. This increase in insulin levels in the blood increases reactive oxygen species production and oxidative stress, resulting in DNA damage. Carvedilol (CRV) is a non-selective beta-blocker, and research has shown that this compound and its metabolites have anti-oxidative properties. Carvedilol can, directly and indirectly, reduce reactive oxygen species (ROS) and has a protective effect on DNA damage from oxidative stress. Given the insolubility of CRV in water, finding new methods to increase its solubility can be an essential step in research. This study aimed to determine whether carvedilol could have a protective effect on insulin-induced genomic damage. Methods: We treated cells with insulin alone, amorphous-CRV alone, and amorphous-CRV and niosomal-CRV with insulin and DNA damage were investigated using the comet method to achieve this goal. Results: Our results showed that insulin in the studied concentration has a significant genotoxic effect and non-cytotoxic at higher concentrations. CRV, both in amorphous and niosome form, reduced insulin-induced DNA damage by reducing ROS production. The comet assay results demonstrate that treating HUVEC cells in pretreatment condition with amorphous-CRV and niosome-CRV significantly reduces DNA damage of insulin.

Preparation and characterization of poly (lactic-co-glycolic acid) nanofibers containing simvastatin coated with hyaluronic acid for using in periodontal tissue engineering.

Periodontal diseases can lead to soft tissue defects. Tissue engineering can provide functional replacements for damaged tissues. Recently, electrospun nanofibers have attracted great interest for tissue engineering and drug delivery applications. This has been revealed that statins exhibit positive impacts on the proliferation and regeneration of periodontal tissues. Electrospun simvastatin loaded poly (lactic-co-glycolic acid) (SIM-PLGA-NF) were prepared using electrospinning technique. Optimal conditions for preparation of SIM-PLGA-NF (PLGA concentration of 30 wt%, voltage of 15 kV, and flow rate of 1.5 ml h-1 ) were identified using a 23 factorial design. The optimized SIM-PLGA-NFs (diameter of 640.2 ± 32.5 nm and simvastatin entrapment efficacy of 99.6 ± 1.5%) were surface modified with 1% w/v hyaluronic acid solution (1%HA- SIM-PLGA-NF) to improve their compatibility with fibroblasts and potential application as a periodontal tissue engineering scaffold. HA-SIM-PLGA NFs were analyzed using SEM, FTIR, and XRD. 1%HA-SIM-PLGA-NF had uniform, bead-free and interwoven morphology, which is similar to the extracellular matrix. The mechanical performance of SIM-PLGA-NFs and release profile of simvastatin from these nanofibers have been also greatly improved after coating with HA. In vitro cellular tests showed that the proliferation, adhesion, and differentiation of fibroblast cells positively enhanced on the surface of 1%HA- SIM-PLGA-NF. These results demonstrate the potential application of 1%HA-SIM-PLGA-NFs as a scaffold for periodontal tissue engineering.

Inhibition of aldehyde dehydrogenase by furazolidone nanoemulsion to decrease cisplatin resistance in lung cancer cells.

Aim: The overexpression of aldehyde dehydrogenase (ALDH) in cancer cells contributes to therapeutic resistance. Furazolidone (FUR) is a strong ALDH inhibitor. Methods: FUR nanoemulsion (NE) was formulated and tested for ALDH inhibitory activity in comparison with free FUR. The cytotoxic potential of cisplatin was evaluated in combination with free FUR and FUR NE. Results: The optimized FUR NE showed droplet size of 167.9 ± 3.1 nm and drug content of 84.2 ± 2.3%. FUR NE inhibited 99.75 ± 2.1% of ALDH activity while 25.0 ± 4.6% was inhibited by free FUR. FUR NE increased the sensitivity to cisplatin in A549 cells by more than tenfold by its ALDH inhibitory effects. Conclusion: This finding can be a promising approach to improve cancer survival in ALDH-positive drug-resistant cancers.

Phytochemical standardization, formulation and evaluation of oral hard gelatin capsules from Pinus eldarica bark extract.

OBJECTIVE: The extract of Pinus eldarica bark contains many polyphenolic compounds that were studied due to their high antioxidant, anti-inflammatory and anti-mutagenic effects. Therefore, the purpose of the present study was to conduct phytochemical standardization and develop hard gelatin capsules from the extract of P. eldarica bark. MATERIALS AND METHODS: Extraction was carried out by maceration method at room temperature for 72 hr using ethanol 70% followed by freeze drying. Quantification and standardization tests were performed using Folin-Ciocalteu method. Then, nine formulations were prepared containing different amounts of stearic acid (1-3%) and corn starch (3%, 10%, and 25%). Each formulation was characterized by FTIR and pharmacopoeial tests such as drug content, disintegration time, flowability parameters and drug release percent. The optimized formulation underwent stability studies at 75±5% humidity and 40±2°C. RESULTS: The total phenolic content of the extract in terms of gallic acid equivalent was 362.8±5.4 mg/g and the total procyanidin content in the extract was 174.386±2.5 mg/g. FTIR revealed no interaction between the components. The results presented that the best formulation of the capsules was achieved they contained 3% of stearic acid and 25% of corn starch. This formulation showed 91.69±0.33% of drug content, 9.36±0.02 min disintegration time and 83.02±0.81% release percent. Moreover, it showed good flowability. Stability studies on the optimized formulation displayed that the formulation was stable within 6 months in the accelerated condition. CONCLUSION: In conclusion, results of the present phytopharmaceutical evaluations confirmed this product as a promising herbal capsule formulation.

Comparison of Efficacy and Peripheral Neuropathy of Solvent-based Paclitaxel with Paclitaxel Poliglumex and NK105: A Systematic Review and Metaanalysis.

Background and Introduction: Peripheral neuropathy is one of the most common dose-limiting side effects of solvent-based paclitaxel. Paclitaxel poliglumex (PPX) and NK105 were developed to overcome the paclitaxel induced peripheral neuropathy. However, the incidence of peripheral neuropathy induced by PPX and NK105 was reported higher than solvent-based paclitaxel, but evidence remains inconsistent. METHODS: The article was reported in accordance with PRISMA Guidelines (Registration number: CRD42021245313). We conducted a meta-analysis to compare the incidence and severity of peripheral neuropathy between solvent-based paclitaxel, PPX and NK105 mono-chemotherapy. RESULTS: Results revealed that no significant difference exists between the incidence of all grade peripheral neuropathy among the solvent-based paclitaxel, PPX and NK105 treated groups. While, the incidence of high grade peripheral neuropathy induced by NK105 was lower than two other groups. Moreover, the overall survival was not improved in PPX compared with other groups. However, NK105 demonstrated significant longer overall survival in patients with cancer. CONCLUSION: Current evidence suggests more attention should be paid to the paclitaxel poliglumex re-formulation.

Preparation and characterization of polypills containing aspirin and simvastatin using 3D printing technology for the prevention of cardiovascular diseases.

Three-dimensional (3D) printing has become a promising manufacturing technique for pharmaceutical products. Fused deposition modeling (FDM) is the most affordable printing technology. But this technique has two major drawbacks: limited drug-loading capacity and the stability of thermolabile drugs. So, other techniques such as melt casting could be associated with FDM to overcome these limitations. In the melt casting method, the drug is mixed with a molten polymer and is poured in the mold and allowed to solidify. The present study for the first time describes the preparation of a multi-compartment polypill permits the physical separation of incompatible drugs by combination of FDM and melt casting techniques. A two-compartment polypill was made using FDM by Eudragit® L100-55 and simultaneously its compartments were filled by aspirin and simvastatin containing molten PEG 6000. Simultaneous usage of FDM and melt casting techniques could increase the drug-loading capacity of 3D-printed polypills. The low temperatures used in melt casting and the absence of solvent in this method would warrant the integrity of polypills, the complete separation of incompatible drugs, and their stability. The prepared polypills showed good uniformity in drug content which confirms the precision of FDM and melt casting techniques. Drug interaction was investigated before and after the accelerated stability test using DSC, which showed that 3D-printed polypills successfully preserved drugs from the interaction. For the first time, this study demonstrates the feasibility of the combination of FDM and melt casting techniques as an innovative platform for CVD polypills production.

A protocol for irradiation of cell lines cultured in multi-well plates: effect of air inhomogeneity on irradiated cell survival.

Introduction: In multi-well cell culture plates, wells are bordered by air cavities. The air cavity inhomogeneities can reduce the amount of delivered dose. In this study, the effect of these cavities on cell survival was investigated.Materials and methods: A special phantom was designed to house the plates and air cavities were filled by water equivalent materials. Cultured melanoma cells were irradiated using 6MV photon for 200 cGy. MTT and clonogenic assay tests were used to evaluate cell survival.Results: Results of MTT assay showed mean survival percentage for irradiated cells in the first group, i.e. plates with air cavities, was 18.9% higher than the second group with air cavities filled with paraffin. Clonogenic assay results showed a maximum of 37% difference in the mean of number of colonies between the first group and the second group (p value < .05).Conclusions: The presence of air cavities in multi-well cell culture plates reduced radiation cell kill by up to 37%. To ensure the accuracy of delivered dose, it is necessary to replace the air cavities as well as the air surrounding the plates by a water equivalent material.

Nanocrystalline cellulose-hyaluronic acid composite enriched with GM-CSF loaded chitosan nanoparticles for enhanced wound healing.

In recent years, applications of biopolymers such as hyaluronic acid (HA) for wound dressing have attracted more attention. However, the poor mechanical properties of HA-based wound dressings limit their clinical applications. Incorporation of reinforcing agents such as nanocrystalline cellulose (CNC) in HA-based wound dressings can improve their mechanical properties. In addition, controlled delivery of growth factors to the wound site using nanoparticles can significantly improve the healing process. In this study, we focus on development and characterization of a novel CNC reinforced HA-based composite containing chitosan nanoparticles loaded with GM-CSF (CNC-HA/GM-CSF-Chi-NPs composite) as an effective wound dressing. CNC-HA/GM-CSF-Chi-NPs composite showed some physicochemical characteristics such as appropriate mechanical properties, high swelling capacity (swelling ratio: 2622.1% ± 35.2%) and controlled release of GM-CSF up to 48 h which make it an excellent candidate for wound dressing. In vivo investigation showed that, after 13 d, the wounds covered with CNC-HA/GM-CSF-Chi-NPs composite could reach to nearly full wound closure and complete re-epithelialization compared to the normal saline treated wounds which exhibited nearly 70% of wound size reduction. Furthermore, the CNC-HA/GM-CSF-Chi-NPs composite treated wounds exhibited significantly lower inflammatory reaction, enhanced re-epithelialization and improved granulation tissue formation compared with CNC-HA/Chi-NPs composite treated wound; it might be due to positive effects of GM-CSF on the wound healing process. Our results suggest that CNC-HA/GM-CSF-Chi-NPs composite can be potentially applied in clinical practice for wound treatment.

Incorporation of rosuvastatin-loaded chitosan/chondroitin sulfate nanoparticles into a thermosensitive hydrogel for bone tissue engineering: preparation, characterization, and cellular behavior.

Rosuvastatin (RSV) has been shown to have significant impact on the simulation of bone regeneration after local injection. The current study aimed to develop a localized controlled delivery system from RSV by incorporating RSV-loaded chitosan/chondroitin sulfate (CTS/CS) nanoparticles into thermosensitive Pluronic F127/hyaluronic acid (PF127/HA) hydrogel. RSV-loaded CTS/CS nanoparticles were prepared by ionic gelation, and the impact of various formulation variables was assessed using the Box-Behnken design. Consequently, optimized RSV-loaded nanoparticles were incorporated into the PF127/HA hydrogel. Rheological properties, degradation rates of hydrogels, and the release rate of RSV from hydrogel were examined. Mean particle size, zeta potential, entrapment efficiency, and mean release time of the optimized RSV-loaded nanoparticles were confirmed as 283.2 ± 16 nm, -31.2 ± 6.8 mV, 63.1 ± 4.2%, and 6.14 ± 0.3 h, respectively. The hydrogel containing 3% w/v CTS/CS nanoparticles existed as a solution with low viscosity at room temperature converted to a semisolid upon increasing the temperature to 35 °C. Hydrogel engrafted with CTS/CS showed controlled release of RSV during 48 h with superior in vitro gel stability. As revealed by cytotoxicity and mineralization assays, incorporation of RSV-loaded particles into PF127/HA hydrogel led to improvement in osteoblast viability and proliferation.

Arginine Functionalized Bacterial Cellulose Nanofibers Containing Gel as an Effective Wound Dressing: In vitro and In vivo Evaluation.

BACKGROUND: Nanofibers such as bacterial cellulose nanofibers (BC-NFs) have gained increasing attention for use in wound dressings. Topical application of arginine can stimulate wound healing significantly. OBJECTIVE: In order to promote the wound healing process, arginine functionalized BC-NFs containing gel (Arg-BC-NFs gel) was prepared by the electrostatic attachment of arginine on the surface of BCNFs. METHOD: The effect of pH was evaluated on the amount of the attached arginine on the BC-NFs surface. The attachment of arginine on BC-NFs surface was investigated by FTIR spectroscopy. The morphology of Arg-BC-NFs was evaluated using FESEM. The viscosity and spreadability of Arg-BC-NFs and the release of arginine from Arg-BC-NFs were evaluated. The effectiveness of Arg-BC-NFs gel was assessed in a full thickness wound model in rats. Re-epithelization, collagen deposition and neovascularization were investigated in the wound tissues using histological and immunohistochemical analysis. RESULTS: FTIR spectra and the zeta potential of BC-NFs confirmed the surface modification of BC-NFs by arginine. FESEM images showed the nanofibrous structure of Arg-BC-NFs. The release of arginine from Arg-BC-NFs gel was in a sustained release manner for 24 h. The appropriate viscosity and spreadability of Arg-BC-NFs gel confirmed its easy topical application. In vivo studies revealed that Arg-BCNFs gel promoted wound closure at a faster rate than BC-NFs gel and arginine solution. Moreover, faster and more organized re-epithelialization, angiogenesis and collagen deposition were achieved in Arg-BC-NFs gel treated group in comparison to other groups. CONCLUSION: Arg-BC-NFs gel can be introduced as an effective wound dressing for acute wounds.