Biocellulose-based hydrogel dressing as a strategy for the management of chronic arterial wounds.

PURPOSE: To evaluate using a biocellulose-based hydrogel as an adjuvant in the healing process of arterial ulcers. METHODS: A prospective single group quasi-experimental study was carried out with chronic lower limb arterial ulcer patients. These patients received biocellulose-based hydrogel dressings and outpatient guidance on dressing and periodic reassessments. The primary outcomes were the ulcer-healing rate and product safety, which were assessed by ulcer area measured in photographic records of pre-treatment and posttreatment after 7, 30, and 60 days. Secondary outcomes were related to clinical assessment by the quality-of-life scores (SF-36 and EQ-5D) and pain, evaluated by the visual analogue scale (VAS). RESULTS: Seventeen participants were included, and one of them was excluded. Six patients (37%) had complete wound healing, and all patients had a significant reduction in the ulcer area during follow-up (233.6mm2 versus 2.7mm2) and reduction on the score PUSH 3.0 (p < 0.0001). The analysis of the SF-36 and EQ-5D questionnaires showed a statistically significant improvement in almost all parameters analyzed and with a reduction of pain assessed by the VAS. CONCLUSIONS: The biocellulose-based hydrogel was safe and showed a good perspective to promoting the necessary conditions to facilitate partial or complete healing of chronic arterial ulcers within a 60-day follow-up. Quality of life and pain were positively affected by the treatment.

Oleogels for the ocular delivery of epalrestat: formulation, in vitro, in ovo, ex vivo and in vivo evaluation.

The ocular administration of lipophilic and labile drugs such as epalrestat, an aldose reductase inhibitor with potential for diabetic retinopathy treatment, demands the development of topical delivery systems capable of providing sufficient ocular bioavailability. The aim of this work was to develop non-aqueous oleogels based on soybean oil and gelators from natural and sustainable sources (ethyl cellulose, beeswax and cocoa butter) and to assess their reproducibility, safety and efficiency in epalrestat release and permeation both ex vivo and in vivo. Binary combinations of gelators at 10% w/w resulted in solid oleogels (oleorods), while single gelator oleogels at 5% w/w remained liquid at room temperature, with most of the oleogels displaying shear thinning behavior. The oleorods released up to 4 µg epalrestat per mg of oleorod in a sustained or burst pattern depending on the gelator (approx. 10% dose in 24 h). The HET-CAM assay indicated that oleogel formulations did not induce ocular irritation and were safe for topical ocular administration. Corneal and scleral ex vivo assays evidenced the permeation of epalrestat from the oleorods up to 4 and 2.5 µg/cm2 after six hours, respectively. Finally, the capacity of the developed oleogels to sustain release and provide significant amounts of epalrestat to the ocular tissues was demonstrated in vivo against aqueous-based niosomes and micelles formulations loaded with the same drug concentration. Overall, the gathered information provides valuable insights into the development of oleogels for ocular drug delivery, emphasizing their safety and controlled release capabilities, which have implications for the treatment of diabetic neuropathy and other ocular conditions.

Toward a greener multifunctional pharmaceutical excipient: in vivo safety evaluation of nanofibrillated cellulose from tobacco stalk.

Tobacco stalk is a cellulose-rich material and a sustainable alternative to be applied as a plant-based nanofibrillated cellulose (NFC) source. NFC use has garnered attention in the development of oral pharmaceutical forms, despite concerns about its safety due to the adverse effects of nicotine on health. Therefore, we aimed at establishing the safety of NFC derived from tobacco stalk for its potential use as a novel pharmaceutical excipient, exploring its potential functions for tablet production. We conducted acute and subchronic oral toxicity tests in adult female Wistar rats. Initially, individual animals received sequential doses (175-5,000 mg·kg-1) for 24 hours followed by a careful observation of any toxic effects. Subsequently, 20 rats were divided into four groups for a subchronic assay, evaluating toxicity signs, body weight changes, hematological, biochemical, and histopathological parameters. No deaths or other clinical toxicity signs were observed in either the acute or the subchronic assays. We noticed a significant reduction in body weight gain (p < 0.05) after 14 days. We found statistical differences for hematological and biochemical parameters, unrelated to dosage. There were no observed toxic effects, and tobacco stalk ingestion did not adversely affect organ morphology in the histopathological evaluation. The oral administration of NFC at 5,000 mg·kg-1 per day for 28 days was well-tolerated by treated rats, with no reported deaths. In conclusion, NFC derived from tobacco stalk has shown to be a sustainable and safe alternative for use as an excipient at experimental doses, demonstrating compatibility with its proposed applications.

Caffeine Mouth Rinse Plus Ingestion Improves the 10-Km Time Trial Compared to Caffeine Mouth Rinse Alone.

Background: The benefits of caffeine to physical performance have been extensively demonstrated, however, it has recently been speculated that there is an effect of the administration route on its effectiveness. Purpose: The current study investigated the effect of caffeine mouth rinse in isolation or combined with ingestion on performance in a 30-minute constant-load exercise followed by a 10-km cycling time trial. Methods: Ten physically active men performed a 30-minute constant-load exercise at 50% of the graded test Wmax, followed by a 10-km cycling time trial. Before and at the middle points of the constant-load exercise and 10-km cycling time trial, the following conditions were administered: PLA (cellulose ingestion plus mouth rinsing with magnesium sulfate), ING (5 mg.kg-1 of caffeine ingestion plus mouth rinsing with magnesium sulfate), MR (cellulose ingestion plus mouth rinsing with 1.2% caffeine), and COMB (5 mg.kg-1 of caffeine ingestion plus mouth rinsing with 1.2% caffeine). Results: During the 30-minute constant-load exercise, COMB presented a lower rating of perceived exertion (RPE) than MR (p = .04). For the 10-km time trial, the COMB was faster than MR (MR = 1363 ± 345 vs. COMB = 1291 ± 308s, Δ% = 5.57, p = .05). Mean power output was higher in COMB than PLA, ING, and MR (234 ± 15 vs. 169 ± 29, 148 ± 11, and 145 ± 12 W, respectively). There were no differences between conditions for heart rate and RPE during the 10-km time trial. Conclusion: In summary, caffeine mouth rinsing potentiated the effects of caffeine ingestion during the 10-km time trial compared to caffeine mouth rinsing alone.

Effect of hydroxyethyl cellulose soluble hemostatic gauze on hemostasis in facial contouring surgery.

BACKGROUND: In facial contour surgery, due to the narrow field of vision in the oral approach and the abundant blood supply to the maxillofacial area, hemostasis is not easy. The purpose of this study was to evaluate the hemostatic effect of soluble hemostatic gauze. METHODS: We organized a prospective randomized study of 282 patients receiving facial contouring surgery (4 types of procedures in total) during 2016.1.1 to 2018.12.30. For each type of procedure, patients were randomly divided into study group (received hemostatic gauze) and control group (received sterile gauze). Two groups were compared for each type of procedure regarding 5 major perioperative variables: intraoperative blood loss, operation time, 24-hour postoperative drainage volume, total postoperative drainage volume, and postoperative drainage time. Correlation between variables was analyzed. RESULTS: Compared with control group, the study group had higher amount of intraoperative blood loss in mandibular angle ostectomy (MAO) (P < .01) and mandibular angle-body-chin curved ostectomy procedures (P < .05), less total postoperative drainage volume in MAO (P < .01) but not in malarplasty with MAO and partial masseter muscle resection along with MAO procedures. No significant difference was observed between respective study and control groups regarding operation time, 24-hour postoperative drainage volume, and postoperative drainage time in any of the 4 types of surgery. In all 4 types of procedures, a strongly positive correlation was observed between total drainage volume and 24-hour drainage volume in both the study and control groups (r: 0.88-0.97, P < .01). CONCLUSION: The effect of hydroxyethyl cellulose soluble hemostatic gauze on hemostasis in facial contouring surgery is associated with the type of surgery, which can reduce the risk of postoperative bleeding in MAO. However, for surgery with relatively large amount of intraoperative and postoperative bleeding, the hemostatic gauze had a limited postoperative hemostasis efficacy, which needs further evaluation.

Gut microbiota mediate the FGF21 adaptive stress response to chronic dietary protein-restriction in mice.

Chronic dietary protein-restriction can create essential amino acid deficiencies and induce metabolic adaptation through the hepatic FGF21 pathway which serves to maintain host fitness during prolonged states of nutritional imbalance. Similarly, the gut microbiome undergoes metabolic adaptations when dietary nutrients are added or withdrawn. Here we confirm previous reports that dietary protein-restriction triggers the hepatic FGF21 adaptive metabolic pathway and further demonstrate that this response is mediated by the gut microbiome and can be tuned through dietary supplementation of fibers that alter the gut microbiome. In the absence of a gut microbiome, we discover that FGF21 is de-sensitized to the effect of protein-restriction. These data suggest that host-intrinsic adaptive pathways to chronic dietary protein-restriction, such as the hepatic FGF21 pathway, may in-fact be responding first to adaptive metabolic changes in the gut microbiome.

Randomized, Double-Blind, Placebo-Controlled Study of Poly-L-Lactic acid for Treatment of Cellulite in the Lower Extremities.

BACKGROUND: Poly-l-lactic acid (PLLA) is an injectable volumizer with biostimulatory properties used for volumetric structural rejuvenation in patients with facial fat volume loss but has increasingly been utilized for off-face applications. OBJECTIVE: The objectives of this randomized, double-blind, placebo-controlled single center study was to assess the safety and effectiveness of PLLA for the treatment of lower extremity cellulite in adult women. METHODS: 31 healthy women were enrolled in the study. Eligible subjects received 3 treatments every 4 weeks with either PLLA (treatment group) or saline (control group) injections combined with subcision, into each of the glutes or thighs. Follow-up visits were at 1, 3, and 6 months after treatment. Assessments included live ratings, rating of standardized pictures by a blinded evaluator, patient questionnaires, safety, and tolerability ratings. RESULTS: At the 3 and 6-month follow-up, there was a statistically significant change in the global aesthetic improvement scale (GAIS) compared to baseline as assessed by blinded investigators. Significant improvements were shown in the cellulite severity scale (CSS) as well as in the subject satisfaction questionnaires. Treatments were found to be tolerable, and no severe treatment-related adverse events occurred. CONCLUSION: Repeated PLLA treatments combined with subcision are effective and safe in improving the appearance of cellulite. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5380.

Alleviating neuropathy of diabetic foot ulcer by co-delivery of venlafaxine and matrix metalloproteinase drug-loaded cellulose nanofiber sheets: production, in vitro characterization and clinical trial.

BACKGROUND: The objective of the present study was co-delivery of venlafaxin (VEN) and doxycycline (DOX), a matrix metalloproteinase inhibitor drug, for alleviating inflammation and neuropathy in diabetic foot ulcer (DFU). METHODS: Bacterial cellulose nanofiber sheets (BCNS) were loaded with DOX and VEN and categorized by their loading efficiency, release profiles and ex vivo permeation throughrat skin. The optimized nanofibers were used in patients with DFU to compare with the standard wound care regimen during a 12-week trial. Wound area was measured every 2 weeks. Biochemical parameters and microscopic studies of the skin were examined prior and at the end of the treatment. The Michigan Neuropathy Screening Instrument (MNSI) questionnaire was utilized to assess diabetic neuropathy. RESULTS: The optimum formulation showed loading efficiency of 37.8 ± 1.6% for DOX and 48 ± 1.9% for VEN. Rat skin permeation was 40% for DOX after 7-29 h and 83% for VEN during 105 h. Patients treated with BCNS showed no significant difference in their biochemical parameters before and after intervention. The ulcer size showed faster reduction after 12 weeks in the treatment group compared to the control group. The abnormal responses in the MNSI questionnaire decreased and pain-free walking distance increased significantly in the treatment group compared with the control group (p < 0.001). Microscopic studies of the skin after using nanofibers showed a large number of polymorphonuclear chronic inflammatory cells and formation of new capillary beds. CONCLUSIONS: The BCNS loaded with DOX and VEN may expedite healing and reduce neuropathy in the DFU of diabetic patients.

The role of rye bran and antibiotics on the digestion, fermentation process and short-chain fatty acid production and absorption in an intact pig model.

The effects of arabinoxylan (AX)-rich rye bran based diet (RB) and antibiotics on digestion, fermentation and short-chain fatty acids (SCFA) absorption were studied compared with an iso-dietary fibre (DF) cellulose based diet (CEL). Thirty female pigs (body weight 72.5 ± 3.9 kg) were fed a standard swine diet in week 1, CEL as wash-out for bran-associated bioactive components in week 2 and then divided into 3 groups fed either the CEL (n = 10) or RB (n = 20) for 2 weeks, where 10 pigs from RB had daily intramuscular antibiotic injections (RB+) and the other 10 pigs were untreated (RB-) in week 4. In RB, the degradation of AX mainly occurred in caecum and proximal colon (P < 0.01) and to a higher extent than cellulose, which on the other hand, irrespective of antibiotic treatment, was less degraded in the RB groups than in the CEL (P < 0.01). The apparent digestibility of fat and protein in the distal small intestine was lower for RB than CEL (P < 0.05), the protein digestibility remained lower in most of the colon, and the digestibility was not affected by treatment with antibiotics. The colonic concentrations of SCFA, acetate and propionate as well as the butyrate concentration in the distal colon were lower with the RB treatments compared with CEL (P < 0.01). Caecal butyrate concentrations were on the other hand higher, and a significant reduction was seen with antibiotic treatment (P < 0.001). The daily net absorption of SCFA and acetate was lower with RB than with CEL (P < 0.01). In conclusion, RB resulted in different DF degradation processes and SCFA production compared with CEL, whereas antibiotic treatment had marginal effects on the intestinal DF degradation but hampered butyrate production.

Topical microbicides for preventing sexually transmitted infections.

BACKGROUND: This is a updated version of our Cochrane Review published in Issue 6, 2012. Sexually-transmitted infections (STIs) continue to rise worldwide, imposing an enormous morbidity and mortality burden. Effective prevention strategies, including microbicides, are needed to achieve the goals of the World Heath Organization (WHO) global strategy for the prevention and control of these infections. OBJECTIVES: To determine the effectiveness and safety of topical microbicides for preventing acquisition of STIs, including HIV. SEARCH METHODS: We undertook a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CLIB, Web of Science, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and reference lists of relevant articles up to August 2020. In addition, we contacted relevant organisations and experts. SELECTION CRITERIA: We included randomised controlled trials of vaginal microbicides compared to placebo (except for nonoxynol-9 because it is covered in related Cochrane Reviews). Eligible participants were sexually-active non-pregnant, WSM and MSM, who had no laboratory confirmed STIs. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected studies, extracted data, and assessed risks of bias in duplicate, resolving differences by consensus. We conducted a fixed-effect meta-analysis, stratified by type of microbicide, and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included eight trials from the earlier version of the review and four new trials, i.e. a total of 12 trials with 32,464 participants (all WSM). We did not find any eligible study that enrolled MSM or reported fungal STI as an outcome. We have no study awaiting assessment. All 12 trials were conducted in sub-Saharan Africa, with one having a study site in the USA, and another having a site in India. Vaginal microbicides tested were BufferGel and PRO 2000 (1 trial, 3101 women), Carraguard (1 trial, 6202 women), cellulose sulphate (2 trials, 3069 women), dapivirine (2 trials, 4588 women), PRO 2000 (1 trial, 9385 women), C31G (SAVVY) (2 trials, 4295 women), and tenofovir (3 trials, 4958 women). All microbicides were compared to placebo and all trials had low risk of bias. Dapivirine probably reduces the risk of acquiring HIV infection: risk ratio (RR) 0.71, (95% confidence interval (CI) 0.57 to 0.89, I2 = 0%, 2 trials, 4588 women; moderate-certainty evidence). The other microbicides may result in little to no difference in the risk of acquiring HIV (low-certainty evidence); including tenofovir (RR 0.83, 95% CI 0.68 to 1.02, cellulose sulphate (RR 1.20, 95% CI 0.74 to 1.95, BufferGel (RR 1.05, 95% CI 0.73 to 1.52), Carraguard (RR 0.89, 95% CI 0.71 to 1.11), PRO 2000 (RR 0.93, 95% CI 0.77 to 1.14), and SAVVY (RR 1.38, 95% CI 0.79 to 2.41). Existing evidence suggests that cellulose sulphate (RR 0.99, 95% CI 0.37 to 2.62, 1 trial, 1425 women), and PRO 2000 (RR 0.95, 95% CI 0.73 to 1.23) may result in little to no difference in the risk of getting herpes simplex virus type 2 infection (low-certainty evidence). Two studies reported data on tenofovir's effect on this virus. One suggested that tenofovir may reduce the risk (RR 0.55, 95% CI 0.36 to 0.82; 224 participants) while the other did not find evidence of an effect (RR 0.94, 95% CI 0.85 to 1.03; 1003 participants). We have not reported the pooled result because of substantial heterogeneity of effect between the two studies (l2 = 85%). The evidence also suggests that dapivirine (RR 1.70, 95% CI 0.63 to 4.59), tenofovir (RR 1.27, 95% CI 0.58 to 2.78), cellulose sulphate (RR 0.69, 95% CI 0.26 to 1.81), and (Carraguard (RR 1.07, 95% CI 0.75 to 1.52) may have little or no effect on the risk of acquiring syphilis (low-certainty evidence). In addition, dapivirine (RR 0.97, 95% CI 0.89 to 1.07), tenofovir (RR 0.90, 95% CI 0.71 to 1.13), cellulose sulphate (RR 0.70, 95% CI 0.49 to 0.99), BufferGel (RR 0.97, 95% CI 0.65 to 1.45), Carraguard (RR 0.96, 95% CI 0.83 to 1.12), and PRO 2000 (RR 1.01, 95% CI 0.84 to 1.22) may result in little to no difference in the risk of acquiring chlamydia infection (low-certainty evidence). The evidence also suggests that current topical microbicides may not have an effect on the risk of acquiring gonorrhoea, condyloma acuminatum, trichomoniasis, or human papillomavirus infection (low-certainty evidence). Microbicide use in the 12 trials, compared to placebo, did not lead to any difference in adverse event rates. No study reported on acceptability of the intervention.  AUTHORS' CONCLUSIONS: Current evidence shows that vaginal dapivirine microbicide probably reduces HIV acquisition in women who have sex with men. Other types of vaginal microbicides have not shown evidence of an effect on acquisition of STIs, including HIV. Further research should continue on the development and testing of new microbicides.

Chart Review Presenting Safety of Injectable PLLA Used With Alternative Reconstitution Volume for Facial Treatments.

BACKGROUND: Since the approval of Sculptra Aesthetic, the amount of sterile water used to reconstitute the product has gradually increased in clinical practice. A retrospective chart review was conducted to evaluate patient safety associated with a larger reconstitution volume, and to investigate specific parameters for how Sculptra Aesthetic is used in a real-world clinical setting. OBJECTIVE: The primary objective of the study was to evaluate the safety of Sculptra Aesthetic when using a reconstitution volume of 7 to 10 mL, via collection of adverse events related to the product or injection procedure reported in medical records. METHODS: This was a multi-center, retrospective chart review conducted in the US. Medical records for subjects treated in the facial area with Sculptra Aesthetic reconstituted to 7–10 mL were reviewed to obtain information about demographics, treatment data, and adverse events. Each injector completed a questionnaire regarding reconstitution and injection procedures generally used. RESULTS: There were 4483 treatments performed in 1002 subjects; nearly half (48%) had 3 or 4 treatments during the studied period. Subjects most commonly received treatment in the midface/cheek area (97%), temple (94%), and jawline (54%). All injectors indicated adding lidocaine to the solution, resulting in total volumes of 8–10 mL. Adverse events were reported by 3.6% of subjects, all mild in intensity. Nodules were reported by 4 subjects (0.4%). CONCLUSION: The low number of AEs reported in this retrospective chart review suggests that facial aesthetic treatment with PLLA reconstituted to a final volume of 8–10 mL, including anesthetics, is associated with a favorable risk benefit ratio. J Drugs Dermatol. 2021;20(1):18-22. doi:10.36849/JDD.5631.

Fibrillar pharmacology of functionalized nanocellulose.

Cellulose nanocrystals (CNC) are linear organic nanomaterials derived from an abundant naturally occurring biopolymer resource. Strategic modification of the primary and secondary hydroxyl groups on the CNC introduces amine and iodine group substitution, respectively. The amine groups (0.285 mmol of amine per gram of functionalized CNC (fCNC)) are further reacted with radiometal loaded-chelates or fluorescent dyes as tracers to evaluate the pharmacokinetic profile of the fCNC in vivo. In this way, these nanoscale macromolecules can be covalently functionalized and yield water-soluble and biocompatible fibrillar nanoplatforms for gene, drug and radionuclide delivery in vivo. Transmission electron microscopy of fCNC reveals a length of 162.4 ± 16.3 nm, diameter of 11.2 ± 1.52 nm and aspect ratio of 16.4 ± 1.94 per particle (mean ± SEM) and is confirmed using atomic force microscopy. Size exclusion chromatography of macromolecular fCNC describes a fibrillar molecular behavior as evidenced by retention times typical of late eluting small molecules and functionalized carbon nanotubes. In vivo, greater than 50% of intravenously injected radiolabeled fCNC is excreted in the urine within 1 h post administration and is consistent with the pharmacological profile observed for other rigid, high aspect ratio macromolecules. Tissue distribution of fCNC shows accumulation in kidneys, liver, and spleen (14.6 ± 6.0; 6.1 ± 2.6; and 7.7 ± 1.4% of the injected activity per gram of tissue, respectively) at 72 h post-administration. Confocal fluorescence microscopy reveals cell-specific accumulation in these target tissue sinks. In summary, our findings suggest that functionalized nanocellulose can be used as a potential drug delivery platform for the kidneys.

Enhanced anti-cancer activity by localized delivery of curcumin form PVA/CNCs hydrogel membranes: Preparation and in vitro bioevaluation.

This study targets to develop curcumin-loaded polyvinyl alcohol/cellulose nanocrystals (PVA/CNCs) membrane as localized delivery system for breast/liver cancer. A novel strategy was developed for enhancing encapsulation capacity and maximizing therapeutic efficiency of curcumin-loaded PVA/CNCs membranes. Membranes were prepared by solution-casting method using citric acid as crosslinker. SEM revealed that PVA/CNCs ratio (80:20) was chosen as the optimum for loading curcumin. FT-IR indicated that, curcumin was incorporated into PVA/CNCs in amorphous-phase via intermolecular hydrogen bond between curcumin and membrane components. Curcumin showed biphasic-release through burst-release of 41% of curcumin during the first hour, followed by sustained-release of 70% and 94% during 24 h and 48 h, respectively. In vitro cytotoxicity of PVA/CNCs/Curcumin membrane exhibited a selective inhibition proliferation of breast and liver cancer cells in a concentration-dependent without any toxic effect on normal cells. At high concentration (8 mg/ml) of PVA/CNCs/Curcumin, reduced viability to 35% and 7% of MCF-7 and Huh-7 cells, respectively; meanwhile high HFB-4 normal cell viability ≥80% was investigated. Antimicrobial activity of PVA/CNCs/Curcumin was investigated by multi-drug-resistant strains, and MIC values. PVA/CNCs/Curcumin membranes with concentration (40 mg/ml) showed broad-spectrum antimicrobial activities, thus inhibited ~96-99% of microbial growth. PVA/CNCs/Curcumin membranes could be as promised anti-infective biomaterials for breast and liver cancer wound healing.

Multifunctional bioactive chitosan/cellulose nanocrystal scaffolds eradicate bacterial growth and sustain drug delivery.

Chitosan-based hydrogels have received significant interest in tissue engineering and regenerative medicine applications owing to their superior biocompatibility. However, their applications are restricted owing to their weak mechanical strength. Cellulose nanocrystals (CNCs) are often explored as reinforcing agents to improve the native properties of polymers owing to their superior physicochemical properties. We fabricated a multi-functional hydrogel scaffold of chitosan/CNCs by incorporating different amounts of CNCs into a chitosan (CH) hydrogel. Significant enhancement in the mechanical strength was noted in the CH/CNCs as compared to that in pure CH hydrogel scaffolds. The cytocompatibility of the fabricated scaffolds was monitored in the presence of bone-marrow-derived mesenchymal stem cells (BMSCs). Improved cell viability and mineralization were observed with CH/CNC hydrogel scaffolds than those with pure CH hydrogel scaffolds. Enhanced osteogenic-related gene expression was observed in the CH/CNC hydrogel scaffold environment than that in the control, indicating their osteogenic potential, in addition to enhanced antibacterial activity. Developed composite scaffolds exhibited improved sustained drug release compared to that by pure polymer scaffolds, and this was more sustained in the scaffolds with higher CNC content. Therefore, the fabricated scaffolds may have been used in tissue engineering for osteogenesis, as antibacterial agents, and in sustained drug delivery.

Efficacy of a Quail Eggs-Based Dietary Supplement for Allergic Rhinitis: Results of a Single-Arm Trial.

Previous data suggested the potential treatment effect of a proprietary quail eggs-based blend on allergic rhinitis (AR) symptoms, induced by allergen challenge. We herein aimed to investigate the efficacy and safety of a similar dietary supplement, comprising the bioactive ingredients of quail eggs and the zinc mineral, in the setting of active AR. Adult patients (n = 77), aged 18- 60 years, with mild, intermittent AR were enrolled in this single-arm, open-label trial. Patients' responses were assessed based on peak nasal inspiratory flow (PNIF) measurements at two visits (Day 1/Visit 1 and Day 7/Visit 2) and self-rating of AR-associated symptoms on a Visual Analog Scale (VAS) throughout the entire 7-day study period. PNIF values at 15, 30, 60, 90 and 120 min (Visit 1) following administration of an oral dose of the study product were the primary efficacy endpoint. PNIF values (Visit 1) gradually increased from baseline (pre-treatment), with statistical significance first reached 30 min later (p = 0.002). VAS scores (Visit 1) for all AR symptoms gradually decreased with statistical significance first reached at 15 min (rhinorrhea, p = 0.042; itchy nose, p = 0.001; sneezing p < 0.001), 30 min (nasal congestion, p < 0.001; itchy eyes, p = 0.003) or 60 min (watery eyes, p = 0.04). PNIF improvement and decline of VAS scores were significantly more apparent at Visit one vs. Visit 2. Treatment-emergent adverse events were limited to cough and muscle strain (one patient each). Our results support the efficacy, rapid mode of action and tolerability of the investigated product for symptomatic treatment of mild intermittent AR.

Immediate Use After Reconstitution of a Biostimulatory Poly-L-Lactic Acid Injectable Implant.

BACKGROUND: Poly-L-lactic acid (PLLA) is a biodegradable, synthetic polymer that stimulates collagen production and can improve skin quality, volume, and thickness. The current reconstitution procedure for Sculptra, a PLLA-containing injectable device involves 2 hours standing time before use. OBJECTIVE: To evaluate and validate an immediate-use procedure for reconstituting a PLLA-containing injectable device. METHODS AND MATERIALS: Three batches of the product were shaken for 1 minute immediately after reconstitution with 8 mL of sterile water. Different physicochemical tests including viscosity, concentration of excipients (sodium carboxymethylcellulose and mannitol), pH, and particle size distribution were performed for standing times 0, 2, 24, and 72 hours after immediate shaking, and compared with the standard 2 hours standing time before shaking. The recovery and stability of optional addition of 1 mL of 2% lidocaine hydrochloride was also assessed. RESULTS: All physiochemical parameters evaluated were equivalent, regardless of reconstitution procedure, showing that shaking vigorously for 1 minute dissolves the excipients of the product properly without a required standing time and with no impact to the PLLA particles. There were no differences in lidocaine hydrochloride content of suspensions after 0 and 72 hours. CONCLUSION: The PLLA-containing product can be used immediately after reconstitution including vigorous shaking, as shown from physicochemical analyses. Optional addition of lidocaine hydrochloride is feasible. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5228.

Cellulose nanocrystals of variable sulfation degrees can sequester specific platelet lysate-derived biomolecules to modulate stem cell response.

The surface chemistry of cellulose nanocrystals was engineered to show variable sulfation degrees, which was exploited to modulate platelet lysate-derived biomolecule sequestration and presentation. The protein coronas developed on CNC surfaces were characterized and it was demonstrated how they promote different signaling effects on human adipose-derived stem cell behavior.

Characterization of bacterial cellulose composite films incorporated with bulk chitosan and chitosan nanoparticles: A comparative study.

Ternary composite films containing bulk chitosan (CS) and chitosan nanoparticles (CSNPs) with different concentrations were prepared using bacterial cellulose/poly(vinyl alcohol) as the base film and the composites films were compared. The micromorphology and mechanical, physical, chemical, antibacterial, and optical barrier properties of the composite films were compared. CS incorporation improved the mechanical properties, as the maximum tensile strength was increased to 130.55 ± 9.42 MPa. The dense structure of CSNPs prevented water diffusion and lessened the water content of the composite membranes. The inclusion of CS and CSNPs both reduced the water solubility and water vapor permeability. CS-doped films possessed good transparency, while CSNPs had better ultraviolet-barrier properties (3.84 % of transmittance at 200-280 nm). In addition, CSNPs-embedded membranes exhibited prominent antibacterial properties against Escherichia coli and Staphylococcus aureus, which were much greater than those of CS composite membranes with a maximum bacteriostatic diameter of 10.33 ± 1.55 mm.

Dietary cellulose prevents gut inflammation by modulating lipid metabolism and gut microbiota.

A Western diet comprising high fat, high carbohydrate, and low fiber content has been suggested to contribute to an increased prevalence of colitis. To clarify the effect of dietary cellulose (an insoluble fiber) on gut homeostasis, for 3 months mice were fed a high-cellulose diet (HCD) or a low-cellulose diet (LCD) based on the AIN-93G formulation. Histologic evaluation showed crypt atrophy and goblet cell depletion in the colons of LCD-fed mice. RNA-sequencing analysis showed a higher expression of genes associated with immune system processes, especially those of chemokines and their receptors, in the colon tissues of LCD-fed mice than in those of HCD-fed mice. The HCD was protective against dextran sodium sulfate-induced colitis in mice, while LCD exacerbated gut inflammation; however, the depletion of gut microbiota by antibiotic treatment diminished both beneficial and non-beneficial effects of the HCD and LCD on colitis, respectively. A comparative analysis of the cecal contents of mice fed the HCD or the LCD showed that the LCD did not influence the diversity of gut microbiota, but it resulted in a higher and lower abundance of Oscillibacter and Akkermansia organisms, respectively. Additionally, linoleic acid, nicotinate, and nicotinamide pathways were most affected by cellulose intake, while the levels of short-chain fatty acids were comparable in HCD- and LCD-fed mice. Finally, oral administration of Akkermansia muciniphila to LCD-fed mice elevated crypt length, increased goblet cells, and ameliorated colitis. These results suggest that dietary cellulose plays a beneficial role in maintaining gut homeostasis through the alteration of gut microbiota and metabolites.