Investigation of nano lipid vesicles of methotrexate for anti-rheumatoid activity

Prabhakara Prabhu1, Rakshith Shetty1, Marina Koland1, K Vijayanarayana3, KK Vijayalakshmi2, M Harish Nairy1, GS Nisha11Department of Pharmaceutics, Nitte University, NGSM Institute of Pharmaceutical Sciences, Paneer, Deralakatte, Mangalore, Karnataka, India; 2Department of Applied Zoology, Mangalore University, Konaje, Mangalore, Karnataka, India; 3Department of Pharmacy Practice, Manipal University, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, IndiaBackground: The purpose of this study was to formulate and evaluate nano lipid vesicles of methotrexate (MTX) for its anti-rheumatoid activity.Methods: In this study the principle of both active as well as passive targeting using MTX-loaded stealth liposomes as per the magic gun approach was followed. Stealth liposomes of MTX were prepared by thin-film hydration method using a PEGylated phospholipid-like DSPE-MPEG 2000. Similarly, conventional liposomes were prepared using phospholipids like DPPC and DSPC. Conventional liposomes were coated with a hydrophilic biocompatible polymer like chitosan. They were investigated for their physical properties and in vitro release profile. Further, in vivo screening of the formulations for their anti-rheumatoid efficacy was carried out in rats. Rheumatoid arthritis was induced in male Wistar-Lewis rats using complete Freund’s adjuvant (1 mg/mL Mycobacterium tuberculosis, heat killed in mineral oil).Results: It was found that chitosan coating of the conventional liposomes increased the physical stability of the liposomal suspension as well as its entrapment efficiency. The size of the unsonicated lipid vesicles was found to be in the range of 8–10 µm, and the sonicated lipid vesicles in the range of 210–260 nm, with good polydispersity index. Further, chitosan-coated conventional liposomes and the PEGylated liposomes released the drug for a prolonged period of time, compared to the uncoated conventional liposomes. It was found that there was a significant reduction in edema volume in the rat group administered with the test stealth liposomal formulations and chitosan-coated conventional liposomes (PEGylated and chitosan-coated conventional) compared to that of the control and standard (administered with free MTX) group of rats. PEGylated liposomes showed almost equal efficacy as that of the chitosan-coated conventional liposomes.Conclusion: Lipid nano vesicles of MTX can be administered by intravenous route, whereby the drug selectively reaches the target site with reduced toxicity to other organs.Keywords: methotrexate, stealth liposomes, conventional liposomes, chitosan coating, targeted delivery, anti-rheumatoid efficac

Antimicrobial susceptibility, risk factors and prevalence of bla cefotaximase, temoneira, and sulfhydryl variable genes among Escherichia coli in community-acquired pediatric urinary tract infection

INTRODUCTION: The emergence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has become an important challenge among pediatric patients with community-acquired urinary tract infection (UTI). OBJECTIVES: The aim of this study was to assess the antimicrobial susceptibility patterns, associated risk factors and to survey the frequency of bla cefotaximase (CTX-M), bla temoneira (TEM), and bla sulfhydryl variable (SHV) genotypes in ESBL-producing E. coli isolated from children with community-acquired UTI. METHODS: This was a prospective study conducted from November 2012 to March 2016 in a tertiary care center. E. coli isolated in urine cultures from children aged ≤18 years was identified and confirmed for ESBL production. ESBL-positive strains were screened for ESBL encoding genes. Chi-square test and Fisher’s exact test were used to compare the difference in antibiotic susceptibility with respect to ESBL positive and negative, and binary logistic regression was used to identify the risk factors associated with ESBL production. RESULTS: Among 523 E. coli isolates, 196 (37.5%) were ESBL positive, >90% were resistant to cephalosporins, and 56% were resistant to fluoroquinolones. Least resistance was observed for imipenem, netilmicin, and nitrofurantoin (2%, 8.6%, 15.3%). Association between ESBL production and drug resistance was significant for ceftazidime (P < 0.001), cefixime (P < 0.001), cefotaxime (P = 0.010), ceftazidime-clavulanic acid (P < 0.001), levofloxacin (P = 0.037), and gentamicin (P = 0.047) compared to non-ESBL E. coli. CTX-M gene was the most prevalent (87.5%), followed by TEM (68.4%) and SHV (3.1%). Previous history of UTI and intake of antibiotics were the common risk factors. CONCLUSION: ESBL-producing E. coli from community-acquired pediatric UTI carries more than one type of beta-lactamase coding genes correlating their increased antibiotic resistance. Aggressive infection control policy, routine screening for detecting ESBL isolates in clinical samples, and antimicrobial stewardship are the keys to prevent their dissemination in community settings

Investigating dental structure response to air abrasion: a finite element analysis

Air abrasion particles, propelled by a compressed air stream, remove material from the tooth’s surface. The air abrasion parameter plays an important role in removing the strains or plaque from the teeth. The research outcomes shed light on the stress distribution within dental structures using the finite element approach. Enamel, as the hardest and outermost layer of the tooth, consistently bears the highest stress levels during air abrasion procedures, regardless of whether the impact pressure is set at 80 or 100 psi. While enamel takes the initial force, it gradually transfers these forces to the dentin layer beneath, a denser but slightly less hard tissue. For abrasive particles falling within the 40 μ m to 100 μ m size range, an impact pressure of 80 psi is found to strike an optimal balance between effective material removal and minimizing damage to dental structures. However, when working with larger particles exceeding 100 μ m, increasing the impact pressure to 100 psi becomes preferable to maintain efficiency and precision. The results of this research provide valuable guidance for enhancing dental procedures with a strong focus on patient safety and the maintenance of dental health. It underscores the importance of thoughtfully adjusting parameters like particle size and impact pressure to attain favourable treatment results while prioritizing the health and comfort of patients

Investigating the Influence of All-Ceramic Prosthetic Materials on Implants and Their Effect on the Surrounding Bone: A Finite Element Analysis

This study aims to assess and compare the impact of Monolithic Zirconia (MZ) and In-Ceram Zirconia (ZP) superstructures on stress distribution within implants and D2/D4 bone densities under 200 N vertical and oblique occlusal loads using three-dimensional finite element analysis via ANSYS WORKBENCH R2. The analysis employed maximum and minimum von Mises stress values. Modeling an implant (4.2 mm diameter, 10 mm length) and abutment (0.47 mm diameter), with an 8 mm diameter and 6 mm length single crown, the research identified lower von Mises stresses in D2 cancellous bone with the MZ model under vertical loading. Conversely, under oblique loading, the ZP model exhibited maximum von Mises stresses in D4 bone around the implant. This underscores the critical need to consider physical and mechanical properties, beyond mere aesthetics, for sustained implant success. The findings highlight the effect of material composition and stress distribution, emphasizing the necessity of durable and effective implant treatments