Effect of nanocurcumin supplementation on the severity of symptoms and length of hospital stay in patients with COVID-19: A randomized double-blind placebo-controlled trial.

It has been more than a year since the outbreak of COVID-19, and it is still the most critical issue of the healthcare system. Discovering effective strategies to treat infected patients is necessary to decrease the mortality rate. This study aimed to determine the effects of nanocurcumin on the severity of symptoms and length of hospital stay (LOS) in COVID-19 patients. Forty-eight COVID-19 patients were randomly assigned into nanocurcumin (n = 24) and placebo (n = 24) groups receiving 160 mg/day nanocurcumin or placebo capsules for 6 days. Mean differences of O2 saturation were significantly higher in patients who received nanocurcumin supplements (p = 0.02). Also, nanocurcumin treatment significantly reduced the scores of domains 3 and 4 and the total score of Wisconsin Upper Respiratory System Survey (WURSS-24), indicating milder symptoms in the treatment group (p = 0.01, 0.03, and 0.01 respectively). Besides, the LOS in curcumin groups was lower than in the placebo group, although the difference was not statistically significant (6.31 ± 5.26 vs. 8.87 ± 8.12 days; p = 0.416). CBC/differentiate, hs-CRP level and the pulmonary involvement in CT scan were not different between the two groups. As nanocurcumin can be effective in increasing O2 saturation and reducing the severity of symptoms in COVID-19 patients, it could probably be used as a complementary agent to accelerate the recovery of patients.

Oral nano-curcumin formulation efficacy in management of mild to moderate hospitalized coronavirus disease-19 patients: An open label nonrandomized clinical trial.

Curcumin is proposed as a potential treatment option for coronavirus disease-19 (COVID-19) by inhibiting the virus entrance, encapsulation and replication, and modulating various cellular signaling pathways. In this open-label nonrandomized clinical trial, efficacy of nano-curcumin oral formulation has been evaluated in hospitalized patients with mild-moderate COVID-19. Forty-one patients who fulfilled the inclusion criteria were allocated to nano-curcumin (n = 21) group (Sinacurcumin soft gel, contains 40 mg curcuminoids as nanomicelles, two capsules twice a day) or control (n = 20) group, for 2 weeks. Patients' symptoms and laboratory data were assessed at baseline and during follow-up period. Most of symptoms including fever and chills, tachypnea, myalgia, and cough resolved significantly faster in curcumin group. Moreover, SaO2 was significantly higher in treatment group after 2, 4, 7, and 14 days of follow-up and lymphocyte count after 7 and 14 days. Duration of supplemental O2 use and hospitalization was also meaningfully shorter in treatment group. It is also noteworthy to mention that no patient in treatment group experienced deterioration of infection during follow-up period, but it occurred in 40% of control group. Oral curcumin nano-formulation can significantly improve recovery time in hospitalized COVID-19 patients. Further randomized placebo controlled trials with larger sample size are recommended.

The particle size of drug nanocarriers dictates the fate of neurons; critical points in neurological therapeutics.

Neurological disorders and diseases are on the rise in the world, while pharmacists are being encouraged to encapsulate drugs into the nanocarriers. The critical key question is which size of nanocarrier has a promising neurotherapeutic effect. In the present study, FTY-720, an FDA approved drug, was encapsulated into O/W nanocarriers. SEM and DLS data indicated in ultrasonication and stirring methods resulted in spherical nanocarriers with a particle size of 60 and 195 nm (nF60 and nF195), respectively. Further to investigate the effect of particle size on neuronal cells, MTT assay, PI flow-cytometry, LDH release, and NO production examinations were performed. Results showed that small nanocarriers increased cell viability along with the decline of dead cells, while both nanocarriers decreased LDH release and NO production as compared to the conventional drug. Notably, qRT-PCR and western blotting data related to apoptotic markers indicated in the increase of cell mortality in cells treated by nF190 was not due to the increase of apoptosis and Bax/Bcl2 ratio. It is worth mentioning that integrin α5 as a cell surface receptor involves in neuritogenesis was over-expressed in neuronal cells treated by small nanocarriers. However, nF60 increased PTK2 over-expression along with neurite outgrowth, as well. In other words, nanocarriers at the size of 60 nm are preferred to 195 nm as a drug carrier in neurotherapy due to profound impacts on neural cells. Thanks to small nanocarrier broad positive action on neural viability and neurite outgrowth. The present study discloses a pharmaceutical strategy to design drugs based on their particle size efficiency.

Strong binding active constituents of phytochemical to BMPR1A promote bone regeneration: In vitro, in silico docking, and in vivo studies.

Two of the most problematic orthopedic and neurosurgeon visits are associated with spine and craniofacial fractures. Therefore, more attention needs to be paid to finding a medicine to repair these fractures. Amongst the most mysterious herbs, Aloe vera stands out. In the present study, the ameliorating function of A. vera on osteogenesis was studied in vitro and in vivo. Osteoblast-like cells were exposed to A. vera, followed by analysis of cell viability, lactate dehydrogenase release, and intracellular reactive oxygen species (ROS) production. The results showed an enhanced cell biocompatibility in a dose-dependent manner due to attenuated intracellular ROS production. Furthermore, a docking study indicated that the strong affinity of A. vera constituents to type I bone morphogenic protein receptor (BMPR1A) without the involvement of the BMPR1A chain B. The induction of osteogenesis prompts extracellular calcium deposition by osteoblasts, which affirms successful in vitro bone regeneration. However, injection of A. vera in rats with critical size calvarial defects induced Runx2, alkaline phosphatase (ALP), OCN, and BMP2 genes overexpression, which led to the formation of victorious bone with enhanced bone density and ALP activity. It is worthy to note that Aloin has the highest affinity to BMPR1A, whereas there are no reports regarding the impact of Aloenin, Aloesin, and γ-sitosterol on osteogenesis. Furthermore, some of them have antitumor potency, and it might be proposed that they are considered as a bone substitute in the osteotomy site of osteosarcoma with the aim of bone recovery and suppression of osteosarcoma. The whole consequences of this investigation manifests the plausibility of using A. vera as an antioxidant and osteoconductive substitute.

Thymol reduces acetic acid-induced inflammatory response through inhibition of NF-kB signaling pathway in rat colon tissue.

AIM: The aim of the present study was to evaluate the anti-inflammatory effect of thymol in acetic acid-induced rat colitis through inhibiting the NF-κB signaling pathway. METHODS: Colitis was induced by intra-rectal administration of 2 mL of diluted acetic acid (4%) solution using a flexible plastic rubber catheter in Wistar rats. Colitis was induced on the first day and all treatments were applied 5 days after the induction of colitis. Thymol was dissolved in 0.2% tween 80 in saline and administered orally at doses of 10, 30, and 100 mg/kg per day. Macroscopic and histopathologic investigations were done. The expression of myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) was determined by immunohistochemistry (IHC) assay. The protein expression level of pNF-κB p65 was measured by the Western blot technique. RESULTS: Treatment with thymol reduced mucosal and histological damages compared to the acetic acid group. Our results showed that thymol markedly inhibited the production of MPO and TNF-α in the colon tissue of the acetic acid-induced group. In addition, thymol decreased acetic acid-induced up-regulation of pNFκB p65 protein. CONCLUSIONS: The results of our study suggest that thymol exerts an anti-inflammatory effect in acetic acid-induced rat colitis by inhibiting the NF-κB signaling pathway and downregulating TNF-α and MPO expressions.

Melatonin ameliorates TNBS-induced colitis in rats through the melatonin receptors: involvement of TLR4/MyD88/NF-κB signalling pathway.

AIM: The aim of the present study is to investigate the anti-inflammatory effect of melatonin in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis through the inhibition of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signalling pathway and activation of melatonin receptor. METHODS: Colitis was induced in Wistar rats by administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50% ethanol solution using a flexible plastic rubber catheter into the colon via the anus. This resulted in incidence of colitis on the first day, and all treatments were conducted for 10 days after induction of colitis. Melatonin was administered intraperitoneally (i.p.) at doses of 1, 5, and 10 mg/kg/day. Luzindole (non-selective MT1/MT2 receptor antagonist) was administered i.p. at dose of 5 mg/kg/day 15 min prior to melatonin injection. During the experiment, animals were monitored for the appearance of diarrhoea, body weight loss, and rectal bleeding. Myeloid peroxidase enzyme and tumour necrosis factor-α (TNF-α) activities were detected by immunohistochemistry. The protein expression level of TLR4, myeloid differentiation factor 88 (MyD88), NF-κB p65, and inhibitor of kappa B (I-κB) were detected by western blotting analysis. RESULTS: Treatment with melatonin improved weight loss, mucosal, and histological damage compared with TNBS group. In addition, melatonin decreased TNBS-induced up-regulation of TLR4, MyD88, and NF-κB p65, and increased down-regulation of I-κB proteins. On the other hand, the administration of luzindole resulted in the inhibition of melatonin effects. CONCLUSIONS: It seems that the inhibition of TLR4/NF-κB signalling pathway may mediate the anti-inflammatory effects of melatonin in TNBS-induced rat colitis.

Foeniculum vulgare essential oil ameliorates acetic acid-induced colitis in rats through the inhibition of NF-kB pathway.

AIM: The aim of the present study is to investigate the protective effects of Foeniculum vulgare essential oil on intestinal inflammation through the inhibition of NF-kB pathway in acetic acid-induced rat colitis. METHODS: Acute colitis was induced by intra-rectal administration of 2 mL of diluted acetic acid (4%) solution. Two hours after the induction of colitis, 0.2% tween 80 in normal saline, dexamethasone (2 mg/kg) and F. vulgare essential oil (100, 200, 400 mg/kg) were administered to the animals by oral gavage and continued for 5 consecutive days. Assessment of macroscopic and microscopic lesions was done. MPO activity was evaluated by biochemical method. Furthermore, TNF-α activity was detected by immunohistochemistry (IHC) and the expression level of p-NF-kB p65 protein was measured by western blot analysis. RESULTS: Dexamethasone and F. vulgare essential oil (200, 400 mg/kg) reduced the macroscopic and microscopic lesions compared to the acetic acid group (p < 0.01, p < 0.001). In addition, these agents decreased the activity of MPO (p < 0.01, p < 0.001) and the expression of TNF-α positive cells (p < 0.05, p < 0.01, p < 0.001) in the colon tissue compared to acetic acid group. Furthermore, they inhibited acetic acid-induced expression of p-NF-kB p65 protein (p < 0.05, p < 0.001). CONCLUSION: It is proposed that the anti-inflammatory activity of F. vulgare essential oil on acetic acid-induced colitis in rats may involve the inhibition of NF-kB pathway.

Fluorescent multi-responsive cross-linked P(N-isopropylacrylamide)-based nanocomposites for cisplatin delivery.

Magnetic, pH and temperature-sensitive, poly(N-isopropylacrylamide) (PNIPAM)-based nanocomposites with fluorescent properties were synthesized by free radical copolymerization-cross linking of NIPAM, N,N-dimethylaminoethyl methacrylate (DMAEMA) and 4-acrylamidofluorescein (AFA). The model anti-cancer drug, cisplatin (CDDP), was loaded into the resulted nanogel. For the production of CDDP-loaded nanocomposite, Fe3O4 magnetic nanoparticles (MNPs) and CDDP were loaded into the nanogel. Field-emission scanning electron microscopy (FE-SEM) indicated that the size of nanogel and CDDP-loaded nanocomposite were about 90 and 160 nm, respectively. The encapsulation efficiency of CCDP was found up to 65%. The loaded CCDP showed sustained thermal and pH-responsive drug release. A high level of drug release was observed under the conditions of low pH and high temperature. The lower critical solution temperature (LCST) of synthesized nanogel was about 40 °C. CDDP-loaded nanocomposite showed a volume phase transition from 282 to 128 nm at its LCST. Accordingly, in this study, the synthesized nanocomposite can be employed as a stimuli-responsive anti-cancer drug delivery system and the pH and temperature of solution have the potential to monitor the drug release.

Atorvastatin attenuates TNBS-induced rat colitis: the involvement of the TLR4/NF-kB signaling pathway.

AIM: The aim of the present study is to explore whether atorvastatin improves intestinal inflammation through the inhibition of the TLR4/NFkB signaling pathway in TNBS-induced rat colitis. METHODS: Acute colitis was induced by intra-rectal administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50 % ethanol. Twenty four hours after colitis induction, saline, atorvastatin (20 and 40 mg/kg) and sulfasalazine (100 mg/kg) were given to the animals by oral route. This was repeated daily for 1 week. Body weight changes, macroscopic and microscopic lesions were assessed. MPO and TNF-α activities were detected by immunohistochemistry (IHC) and the expression level of TLR4, MyD88 and NF-κB p65 proteins were measured by western blotting analysis. RESULTS: Atorvastatin and sulfasalazine reduced the body weight loss, macroscopic and microscopic lesions. Additionally, both drugs decreased the expression of MPO and TNF-α positive cells in the colon tissue. Furthermore, they inhibited the TNBS-induced expression of TLR4, MyD88 and NF-κB p65 proteins. CONCLUSIONS: It is suggested that the anti-inflammatory effect of atorvastatin on TNBS-induced rat colitis may involve the inhibition of the TLR4/NFkB signaling pathway.

Mesenteric artery responsiveness to acetylcholine and phenylephrine in cirrhotic rats challenged with endotoxin: the role of TLR4.

Cirrhosis is associated with vascular dysfunction and endotoxemia. These experiments were designed to investigate the hypothesis that the administration of a low-dose of lipopolysaccharide (LPS) worsens vascular dysfunction in rats subjected to bile-duct ligation (BDL), and to determine whether LPS initiates changes in vascular Toll-like receptor 4 (TLR4) expression. Four weeks after BDL, the animals were given an intraperitoneal injection of either saline or LPS (1.0 mg/kg body mass). Three hours later, the superior mesenteric artery was isolated, perfused, and then subjected to the vasoconstriction and vasodilatation effects of phenylephrine and acetylcholine, respectively. Our results show that phenylephrine-induced vasoconstriction decreased in the cirrhotic vascular bed (BDL rats) compared with the vascular bed of the sham-operated animals, and that the LPS injections in the cirrhotic (BDL) rats worsened this response. LPS injection administered to the sham-operated animals had no such effect. On the other hand, both the BDL procedure and the LPS injection increased acetylcholine-induced vasorelaxation, but LPS administration to the BDL rats had no effect on this response. The mRNA levels of TLR4 did not change, but immunohistochemical studies showed that TLR4 localization switched from the endothelium to vascular smooth muscle cells following chronic BDL. In conclusion, acute endotoxemia in cirrhotic rats is associated with hyporesponsiveness to phenylephrine and tolerance to the effects of acetylcholine. Altered localization of TLR4 may be responsible for these effects.

Liposomal factor VIII as an efficient pharmaceutical system for the treatment of hemophilia.

Objectives: Currently, the most important treatment approach for hemophilia type A is recombinant Factor VIII. However, due to its low retention time in the blood, the patients usually need successive injections. In addition, neutralization of injected proteins by antibodies complicates treatment. We examined the prolongation of the persistence time of injectable FVIII in the blood and the potential effects on survival using promising PEGylated liposomes (PEGLip) utilizing hydrogenated soy phosphatidylcholine (HSPC, Tm= 54.5 ºC) and 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC, Tm= - 2 ºC). Materials and Methods: Nanoliposomes with different percentages of PEG (3% and 5%) were obtained via the thin film hydration procedure and extrusion. Liposomal FVIII formulation was prepared and characterization was done. Results: The results revealed that the formulations are in the 80-120 nm range with uniform dispersion, which was confirmed using transmission electron microscopy (TEM) imaging. The phase transition temperature (Tm) of the liposomes was obtained by differential scanning calorimetry (DSC). With an attachment efficacy of approximately 87%, proteins bind non-covalently yet with a strong affinity to the exterior of PEGLip. The final formulations underwent additional examination. No significant change was observed in size, charge, and PDI between the FVIII-conjugated liposomal formulations and their liposomal nanoparticles. The selected formulations were injected into BALB/c mice. The circulation time and potential clotting effectiveness of PEGLip-FVIII are vastly improved over free protein, in non-hemophilic mice. Conclusion: The obtained results showed that using phospholipids with high Tm (HSPC) can improve the hemostatic efficiency of liposomes more than phospholipids with low Tm (POPC).

Effect of nano-curcumin supplementation on angina status, and traditional and novel cardiovascular risk factors in overweight or obese patients with coronary slow flow phenomenon: a randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Cardiovascular events and poor quality of life are frequently observed in patients with coronary slow flow phenomenon (CSFP). This trial evaluated the effect of nano-curcumin supplement containing curcuminoids, as multifunctional nutraceuticals, on angina status, and some traditional and novel cardiovascular risk factors in overweight or obese patients with CSFP. METHODS: In this double-blind, randomized, placebo-controlled clinical trial, 42 overweight or obese patients with CSFP received either 80 mg/day of nano-curcumin or placebo for 12 weeks. Seattle angina questionnaire (SAQ) as a clinical measure of angina status, circulating endocan, adropin, homocysteine, lipid profile, and the novel scores of visceral adiposity index (VAI) and waist-triglyceride index (WTI) were assessed before and after the intervention. The independent samples t-test, Mann-Whitney test, analysis of covariance, Chi-square, and Fisher's exact tests were used where appropriate. RESULTS: All domains of SAQ including physical limitation, angina stability, angina frequency-severity, treatment satisfaction, and disease perception and quality of life improved significantly in the nano-curcumin compared with the placebo group. No significant changes were observed in serum endocan, adropin, and homocysteine following the intervention. Triglycerides, triglyceride/high-density lipoprotein cholesterol ratio, WTI and VAI values improved significantly only within the nano-curcumin group. CONCLUSIONS: Supplementation with 80 mg/day nano-curcumin (containing curcuminoids) for 12 weeks significantly improved clinically important disease-specific aspects of health in patients with CSFP. Some traditional and novel cardiovascular risk factors improved significantly only compared with the baseline values, which need further investigation. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Tehran University of Medical Sciences (IR.TUMS.VCR.REC.1398.794). The study protocol was registered at Iranian Registry of Clinical Trials by IRCT20131125015536N8 registration ID at 19.06.2019.

Effect of nano-curcumin supplementation on cardiometabolic risk factors, physical and psychological quality of life, and depression in patients with coronary slow flow phenomenon: a randomized double-blind clinical trial.

BACKGROUND: Extensive evidence has suggested the cardio-protective properties of the polyphenol curcumin. The aim of this study was to investigate the effects of a highly bioavailable curcumin supplement on cardiometabolic risk factors, health-related quality of life, and depression in patients with coronary slow flow phenomenon (CSFP). METHODS: This randomized double-blind placebo-controlled clinical trial was conducted in 42 patients with CSFP (age 35-70 years, 25 ≤ body mass index < 40 kg/m2). Patients received either 80 mg/day nano-curcumin or placebo for 12 weeks. Serum levels of visfatin, high-sensitivity C-reactive protein (hs-CRP), and glycemic indices were measured before and after the intervention. The short form 36-item quality of life (SF-36) and Beck's Depression Inventory-II (BDI-II) questionnaires were assessed, as well. RESULTS: No significant improvements were observed in circulating hs-CRP and visfatin following the intervention. A significant increase was observed in pre- to post-fasting blood glucose (- 0.9 ± 12.2 vs. 7.7 ± 12.4 mg/dl, p = 0.02) and hemoglobin A1C (- 0.1 ± 0.8 vs. 0.5 ± 0.8%, p = 0.04) levels, in the placebo compared with the intervention group. Physical (8.2 ± 8.1 vs. - 1.2 ± 6.5, p < 0.001) and mental (6.8 ± 11.8 vs. - 1.1 ± 10.4, p = 0.02) component summary scores were significantly improved in the nano-curcumin than the placebo group. Additionally, the number of patients with lower degrees of depression was significantly better in the intervention than the placebo group following the supplementation (p = 0.046). CONCLUSION: Curcumin supplementation prevented deterioration of glycemic control and improved physical and psychological quality of life and depression in patients with CSFP. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT20131125015536N8), June 19, 2019.

On the benefit of magnetic magnesium nanocarrier in cardiovascular toxicity of aluminum phosphide.

The present study was designed to determine the effect of a new (25)Mg(2+)-carrying nanoparticle ((25)MgPMC16) on energy depletion, oxidative stress, and electrocardiographic (ECG) parameters on heart tissue of the rats poisoned by aluminum phosphide (AlP). (25)MgPMC16 at doses of 0.025, 0.05, and 0.1 median lethal dose (LD50 = 896 mg/kg) was administered intravenously (iv) 30 min after a single intragastric administration of AlP (0.25 LD50). Sodium bicarbonate (Bicarb; 2 mEq/kg, iv) was used as the standard therapy. After anesthesia, the animals were rapidly connected to an electronic cardiovascular monitoring device for monitoring of ECG, blood pressure (BP), and heart rate (HR). Later lipid peroxidation, antioxidant power, ATP/ADP ratio, and Mg concentration in the heart were evaluated. Results indicated that after AlP administration, BP and HR decreased while R-R duration increased. (25)MgPMC16 significantly increased the BP and HR at all doses used. We found a considerable increase in antioxidant power, Mg level in the plasma and the heart and a reduction in lipid peroxidation and ADP/ATP ratio at various doses of (25)MgPMC16, but (25)MgPMC16-0.025 + Bicarb was the most effective combination therapy. The results of this study support that (25)MgPMC16 can increase heart energy by active transport of Mg inside the cardiac cells.(25)MgPMC16 seems ameliorating AlP-induced toxicity and cardiac failure necessitating further studies.

Preparation and optimization of acetaminophen nanosuspension through nanoprecipitation using microfluidic devices: an artificial neural networks study.

The purpose of this study was to find an artificial neural networks model for determining major factors impacting the stability of an acetaminophen nanosuspansion that was prepared using nanoprecipitation in microfluidic reactors. Four variables, namely concentration of surfactant, solvent and antisolvent flow rate and solvent temperature were used as input variables and time of sedimentation of nanoparticles was considered as output variable. The particle size of optimized formulation was measured by transmission electron microscope and dynamic light scattering. Comparing the 3D graphs from the model showed that antisolvent flow rate and temperature have direct relation with time of sedimentation, whereas solvent flow rate generally has reverse relation with the time of sedimentation. Concentration of surfactant was found to be the most important factor in determining the stability of nanosuspension.

Investigation of Antioxidant and Anti-inflammatory Properties of Berberine Nanomicelles: In vitro and In vivo Studies.

INTRODUCTION: In the present study, neuroprotective effects of berberine (BBR) and berberine nanomicelle (BBR-NM) against lipopolysaccharides (LPS)-induced stress oxidative were investigated, and compared by evaluating their antioxidant and anti-inflammatory activities in PC12 cells, and rat brains. A fast, green, and simple synthesis method was used to prepare BBR-NMs. METHOD: The prepared BBR-NMs were then characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). In vitro experiments were carried out on the LPS-treated PC12 cell lines to investigate the anti-cytotoxic and antioxidant properties of BBR-NM and BBR. The results showed that BBR-NMs with a diameter of ~100 nm had higher protective effects against ROS production and cytotoxicity induced by LPS in PC12 cells in comparison with free BBR. RESULTS: Moreover, in vivo experiments indicated that the activity levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), increased in the brain of LPS-treated rats administrated with BBR-NM at the optimum dose of 100 mg.kg-1 . BBR-NM administration also resulted in decreased concentration of lipid peroxidation (MDA) and pro-inflammatory cytokines, such as Serum interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α). CONCLUSION: Overall, BBR-NM demonstrated higher neuroprotective effects than free BBR, making it a promising treatment for improving many diseases caused by oxidative stress and inflammation.

Gold cluster encapsulated liposomes: theranostic agent with stimulus triggered release capability.

Cancer is a major cause of death worldwide. Cancer-resistant to chemo or radiotherapy treatment is a challenge that could be overcome by a nanotechnology approach. Providing a theranostic nano-platform for different cancer treatment strategies could be revolutionary. Here we introduce a multifunctional theranostic nanostructure which has the capacity for improving cancer diagnosis and treatment through better chemo and radiotherapy and current x-ray imaging systems through co-encapsulation of a small gold cluster and anticancer drug doxorubicin. 2 nm gold clusters represent good heating under radio frequency electric field (RF-EF) exposure and have been used for in vitro hyperthermia treatment of cancerous cells. Liposomal doxorubicin (169 ± 19.8 nm) with gold clusters encapsulation efficiency of 13.2 ± 3.0% and doxorubicin encapsulation efficiency of 64.7 ± 0.7% were prepared and studied as a theranostic agent with a high potential in different cancer treatment modalities. Exposure to a radiofrequency electric field on prepared formulation caused 20.2 ± 2.1% drug release and twice decreasing of IC50 on colorectal carcinoma cells. X-ray attenuation efficiency of the liposomal gold cluster was better than commercial iohexol and free gold clusters in different concentrations. Finally, treatment of gold clusters on cancerous cells results in a significant decrease in the viability of irradiated cells to cobalt-60 beam. Based on these experiments, we concluded that the conventional liposomal formulation of doxorubicin that has been co-encapsulated with small gold clusters could be a suitable theranostic nanostructure for cancer treatment and merits further investigation.

Effect of a collagen-enriched beverage with or without omega-3 fatty acids on wound healing, metabolic biomarkers, and adipokines in patients with major burns.

BACKGROUND & AIMS: This study investigated the effects of collagen hydrolysate and omega-3 fatty acids (FAs) on the rate and quality of wound healing, metabolic disorders, and adipose-derived peptides in patients with major burns. METHODS: In this randomized clinical trial, 66 patients with 20-45% deep partial or full-thickness burns were randomly assigned to three groups to receive either a beverage containing collagen (40 gr/d), collagen (40 gr/d) plus 3 gr/d omega-3 (ω-3) FAs, or placebo for four weeks. Wound healing rate, Vancouver scar scale (VSS), as well as baseline, weeks two and three serum concentrations of adiponectin, fibroblast growth factor 21 (FGF21), neuregulin 4 (NRG4), transforming growth factor (TGF)-ß1, and pre-albumin/hs-CRP ratio were assessed. RESULTS: The wound healing rate during the weeks post-burn (p = 0.006 and p = 0.01), and days of 95% (21.3 ± 6.8 and 22.9 ± 8.7 vs. 34.3 ± 14.8 days, p = 0.003 and p = 0.03) and complete (26 ± 7.7 and 27.4 ± 9.4 vs. 41.1 ± 16.6 days, p = 0.003 and p = 0.01) wound healing were significantly better with Collagen and Collagen. ω-3 compared to the placebo group. The VSS was significantly lower, indicated better scar status, in the both intervention groups compared to the placebo (p = 0.02 and p = 0.01). Wound healing outcomes were not statistically different between the Collagen and Collagen. ω-3 groups. Hs-CRP/pre-albumin ratio was significantly lower in the Collagen. ω-3 than the placebo group at week three (1.2 ± 1.9 vs. 4.8 ± 7.7 dl/l, p = 0.03). The significant decrease in serum adiponectin seen during the trial course within the placebo (10 ± 8.8 to 5.8 ± 4.9 mg/l, p = 0.03) and Collagen (11.8 ± 14 to 8.6 ± 11.7 mg/l, p = 0.03) groups was prevented in the Collagen. ω-3 group (p = 0.4). Circulating FGF21 decreased significantly within the Collagen (p = 0.005) and Collagen. ω-3 (p = 0.02) groups at the end of week three compared to the baseline. CONCLUSIONS: Adding collagen hydrolysate as part of adjunctive therapy improved wound healing rate and quality. These findings as well as the efficacy of omega-3 FAs need to be further confirmed in larger populations. This study was registered with the Iranian Registry of Clinical Trials (IRCT20090901002394N42).

Characterization of stability, safety and immunogenicity of the mRNA lipid nanoparticle vaccine Iribovax® against COVID-19 in nonhuman primates.

mRNA-lipid nanoparticle (mRNA-LNP) vaccines have proved their efficacy, versatility and unprecedented manufacturing speed during the COVID-19 pandemic. Here we report on the physicochemical properties, thermostability, immunogenicity, and protective efficacy of the nucleoside-modified mRNA-LNP vaccine candidate Iribovax® (also called SNEG2c). Injection of BALB/c mice, rabbits and nonhuman primates with two doses of SNEG2c induced production of high-titers of SARS-CoV-2 spike-specific and receptor-binding domain (RBD)-neutralizing antibodies in immunized animals. In addition to the strong humoral response, SNEG2c elicited substantial Th1-biased T-cell response. Sera from rhesus macaques immunized with a low dose of the vaccine showed robust spike-specific antibody titers 3-24× as high as those in convalescent sera from a panel of COVID-19 patients and 50% virus neutralization geometric mean titer of 1024 against SARS-CoV-2. Strikingly, immunization with SNEG2c completely cleared infectious SARS-CoV-2 from the upper and lower respiratory tracts of challenged macaques and protected them from viral-induced lung and trachea lesions. In contrast, the non-vaccinated macaques developed moderate to severe pulmonary pathology after the viral challenge. We present the results of repeat-dose and local tolerance toxicity and thermostability studies showing how the physicochemical properties of the mRNA-LNPs change over time and demonstrating that SNEG2 is safe, well tolerated and stable for long-term. These results support the planned human trials of SNEG2c.

Effects of processing parameters on particle size of ultrasound prepared chitosan nanoparticles: an Artificial Neural Networks Study.

The pharmacokinetic properties of chitosan nanoparticles have been shown to mainly depend on its particle size. The aim of this study was to concurrently evaluate and model the effective parameters, namely, chitosan concentration, buffer pH, amplitude and time of sonication, on the particle size of chitosan nanoparticles. Chitosan solutions were prepared and sonicated with different values for the above mentioned parameters. The data were then modeled using artificial neural networks (ANNs). The results illustrated that all four input parameters affect the size of prepared chitosan nanoparticles. While a reverse effect was observed between the size and the buffer pH as well as time and amplitude of sonication, the concentration was found to directly influence the particle size. The optimum condition to obtain the minimum size of nanoparticles in the range of 50-200 nm was found to be high values of pH and sonication time (i.e. approximately 4.9 and 500 s, respectively) and amplitude values of more than ~55.