Preparation and Physicochemical Characterization of Hyaluronic Acid-Lysine Nanogels Containing Serratiopeptidase to Control Biofilm Formation.

Remarkable resistance of bacterial biofilms to high doses of antimicrobials and antibiotics is one of their main challenges. Encapsulation of proteolytic enzymes is one of the suggested strategies to tackle this problem. In this regard, the antibacterial and anti-biofilm activity of biocompatible hyaluronic acid- Lysine nanogels containing serratiopeptidase (SRP-loaded HA-Lys nanogel) was assessed against P. aeruginosa and S. aureus strains. SRP-loaded HA-Lys nanogel was prepared using dropping method and optimized by Box-Behnken experimental design. These formulations were studied for physical characterization, release profile, stability, bioactivity, and anti-biofilm effects. The particle size, polydispersity index (PDI), and surface charge were measured by Zetasizer Nano ZS. The average particle size and zeta potential of the optimum sample were 156 nm and -14.1 mV, respectively. SRP release showed an initial burst followed by sustained release and the highest release was around 77%. Enzyme biological activity data revealed the higher efficiency of free SRP compared to SRP-loaded HA-Lys nanogel. The time-kill assay showed that both forms of SRP-loaded HA-Lys nanogel and blank HA-Lys nanogel showed significant antimicrobial activity against examined bacteria in comparison to the free enzyme. The obtained results demonstrated improved anti-biofilm efficacy and down regulation of tested biofilm genes for both SRP-loaded HA-Lys nanogel 100% and blank HA-Lys nanogel 100% compared to SRP 100%.

Evaluation of the association between clinical parameters and ADAM33 and ORMDL3 asthma gene single-nucleotide polymorphisms with the severity of COVID-19.

BACKGROUND: Coronavirus Disease of 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients had varying clinical symptoms and disease severity (mild, moderate, severe, and critical). Several risk factors, including genetic polymorphisms, have been reported to be associated with disease risk and severity. This study aimed to investigate the association of two polymorphisms in the orosomucoid1-like 3 (ORMDL3) and a disintegrin and metalloprotease 33 (ADAM33) asthma-related genes with the severity of COVID-19. MATERIAL AND METHODS: The study included 116 COVID-19 patients with a positive polymerase chain reaction (PCR) test for the SARS-CoV-2 Delta variant. 58 patients with moderate symptoms, 28 patients with severe symptoms, and 30 outpatients with mild symptoms. Genotyping of rs7216389 in the ORMDL3 and rs2280091 in ADAM33 genes was performed by polymerase chain reaction-restriction fragment length polymorphism. Furthermore, records of patients were studied for hematological profiles and biochemical markers. RESULTS: No significant association was found between rs7216389 and rs2280091 and the severity of COVID-19 between different groups of COVID-19 patients. The serum levels of RBC and neutrophil-to-lymphocyte ratio were significantly increased; the erythrocyte sedimentation rate (ESR), and Aspartate transaminase (SGOT) were significantly decreased during treatment in intensive care unit (ICU) patients. The serum levels of red blood cells, Platelets, Urea, Alkaline phosphatase, ESR, Alanine transaminase (SGPT), and SGOT were significantly increased during treatment in hospitalized patients. The serum levels of inflammatory factors, including C-reactive protein (CRP), D-dimer, and Ferritin at the time of admission, were significantly higher in patients admitted to the ICU patients compared to the other group of patients. CONCLUSION: The two polymorphisms studied in this research are not suitable markers for predicting the severity of COVID-19. However, there are significant differences in the amounts of some blood factors in different groups of COVID-19 patients (P < 0.05) and these factors can be used as a marker for the disease severity prediction.

Disulfiram-Loaded Niosomes Reduces Cancerous Phenotypes in Oral Squamous Cell Carcinoma Cells.

OBJECTIVE: Surgery and chemotherapy are the most common therapeutic strategies proposed for oral squamous cell carcinoma (OSCC). However, some of the disadvantages associated with the current methods like unwanted side effects and poor drug response lead the scientist to seek for novel modalities and delivery approaches to enhance the efficacy of treatments. The study aimed to assess the effectiveness of disulfiram (DSF)-loaded Niosomes on cancerous phenotypes of the OSCC cells. MATERIALS AND METHODS: In this experimental study, an optimum formulation of DSF-loaded Niosomes was developed for the treatment of OSCC cells to reduce drug doses and improve the poor stability of DSF in the OSCC environment. The design expert software was utilized to optimize the particles in terms of size, polydispersity index (PDI), and entrapment efficacy (EE). RESULTS: Acidic pH increased the release rate of DSF from these formulations. The size, PDI, and EE of Niosomes were more stable at 4°C compared to 25°C. The results indicated that DSF-loaded Niosomes could induce apoptosis (P=0.019) in the OSCC cells compared to the control group. Moreover, it could reduce colony formation ability (P=0.0046) and also migration capacity of OSCC cells (P=0.0015). CONCLUSION: Our findings indicated that the application of proper dose of DSF-loaded Niosomes (12.5 µg/ml) increases apoptosis, decreases colony formation capacity and declines the migration ability of OSCC cells.

Co-delivery of doxorubicin and paclitaxel via noisome nanocarriers attenuates cancerous phenotypes in gastric cancer cells.

Gastric cancer (GC) is known as a deadly malignancy all over the world, yet none of the current therapeutic regimens have achieved efficacy. this current study has aimed to optimize and reduce treatment doses and overcome multidrug resistance in GC by developing optimum niosomal formulation for the delivery of doxorubicin (DXR), paclitaxel (PTX), and their co-delivery. The particles' size, polydispersity index (PDI), and entrapment efficacy (EE%) were optimized using statistical techniques, i.e., Box-Behnken and Central Composite Design. In contrast to soluble drug formulations, the release rate of medicines from nanoparticles were higher in physiological and acidic pH. Niosomes were more stable at 4 °C, compared to 25 °C. The MTT assay revealed that the IC50 of drug-loaded niosomes was the lowest among all developed formulations. The apoptosis-related genes (CASPASE-3, CASPASE-8, and CASPASE-9) and tumor suppressor genes (BAX, BCL2) were evaluated in cancer cells before and after treatment. In comparison to control cells and cells treated with soluble forms of DXR and PTX, while the expression of BCL2 decreased, the expression of BAX, CASPASE-3, CASPASE-8, and CASPASE-9 was enhanced in cells treated with drug-loaded niosomes. Drug-loaded niosomes inhibited colony formation capacity and increased apoptosis in human AGS gastric cancer cells. Our results indicate that co-delivery of DXR and PTX-loaded niosomes may be an effective and innovative therapeutic approach to gastric cancer.