Diruthenium(II-III)-ibuprofen-loaded chitosan-based microparticles and nanoparticles systems: encapsulation, characterisation, anticancer activity of the nanoformulations against U87MG human glioma cells.

The aim of this work was to investigate novel formulations containing diruthenium(II-III)-ibuprofen (RuIbp) metallodrug encapsulated into the chitosan (CT) biopolymer. Microparticles (RuIbp/CT MPs, ∼ 1 µm) were prepared by spray-drying, and RuIbp/CT-crosslinked nanoparticles (NPs) by ionic gelation (RuIbp/CT-TPP, TPP = tripolyphosphate (1), RuIbp/CT-TPP-PEG, PEG = poly(ethyleneglycol (2)) or pre-gel/polyelectrolyte complex method (RuIbp/CT-ALG, ALG = alginate (3)). Ru analysis was conducted by energy dispersive x-ray fluorescence or inductively coupled plasma atomic emission spectroscopy, and physicochemical characterisation by powder x-ray diffraction, electronic absorption and FTIR spectroscopies, electrospray ionisation mass spectrometry, thermal analysis, scanning electron, transition electron and atomic force microscopies, and dynamic light scattering. The RuIbp-loaded nanosystems exhibited encapsulation efficiency ∼ 20-37%, drug loading∼ 10-20% (w/w), hydrodynamic diameter (nm): 103.2 ± 7.9 (1), 91.7 ± 12.6 (2), 270.2 ± 58.4 (3), zeta potential (mV): +(47.7 ± 2.8) (1), +(49.2 ± 3.6) (2), -(28.2 ± 2.0) (3). Nanoformulation (1) showed the highest cytotoxicity with increased efficacy in relation to the RuIbp free metallodrug against U87MG human glioma cells.

The first isolation and molecular characterization of Mycoplasma capricolum subsp. capripneumoniae Pakistan strain: A causative agent of contagious caprine pleuropneumonia.

PURPOSE: Mycoplasma capricolum subsp. capripneumoniae (Mccp) causes a severe, usually fatal disease in goats known as Contagious Caprine Pleuropneumonia (CCPP). CCPP is listed by OIE as a notifiable animal diseases, causing economic losses in terms of high morbidity and mortality. Thus far, very limited information is available on the molecular characterization of the unique Mccp strains prevalent in Pakistan. The study was aimed to isolate Mccp local strain for the development of diagnostics and vaccines. METHODS: Samples were collected during November 2017-December 2018 at Northern areas of Pakistan from 10 goat flocks each in Gilgit-Baltistan, Chitral, Swat, Buner, and Hazara. 900 samples were collected; nasal swabs (n = 400), tracheal swabs (n = 150) from naturally infected goats showing clinical signs of CCPP, and lungs tissue (n = 200), pleural fluid (n = 150) from goats at necropsy. RESULTS: The clinical signs recorded were mucopurulent nasal discharges, cough, abdominal respiration and hyperthermia. The post-mortem revealed, pulmonary consolidation, fibrinous pleuropneumonia, and accumulation pleural fluid. The fried egg like growth was observed on agar in 16 (4%), 11 (7.3%), 38 (19%), and 24 (16%) nasal swab, tracheal swabs, lungs and pleural fluid samples, respectively. PCR targeting 16S rRNA gene revealed isolates, belongs to Mycoplasma mycoides cluster, in 72 (8%) samples. Forty one (4.5%) isolates were Mccp by specie specific PCR generating an amplicon of 316 bp. CONCLUSIONS: We successfully isolated local strain of Mccp for the first time in Pakistan. This Mccp strain could be further utilized for the development of diagnostics and control measures against Mccp infection in goats.

Cyclen-based Gd3+ complexes as MRI contrast agents: Relaxivity enhancement and ligand design.

Magnetic Resonance Imaging (MRI) is a noninvasive radiology technique used to examine the internal organs of human body. It is useful for the diagnosis of structural abnormalities in the body. Contrast agents are used to increase the sensitivity of this technique. 1,4,7,10-Tetraazacyclododecane (cyclen) is a macrocyclic tetraamine. Its derivatives act as useful ligands to produce stable complexes with Gd3+ ion. Such chelates are investigated as MRI contrast agents. Free Gd3+ ion is extremely toxic for in vivo use. Upon complexation with a cyclen-based ligand, it is trapped in the preformed central cavity of the ligand resulting in the formation of a highly stable Gd3+-chelate. Better kinetic and thermodynamic stability of cyclen-based MRI contrast agents decrease their potential toxicity for in vivo use. Consequently, such agents have proved to be safest for clinical applications. Relaxivity is the most important parameter used to measure the effectiveness of a contrast agent. A number of factors influence this parameter. This article elucidates detailed strategies to increase relaxivity of cyclen-based MRI contrast agents. 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) are two key ligands derived from cyclen. They also act as building blocks for the synthesis of novel ligands. A few important methodologies for the synthesis of DOTA and DO3A derivatives are described. Moreover, the coordination geometry of chelates formed by these ligands and their derivatives is discussed as well. Novel ligands can be developed by the appropriate derivatization of DOTA and DO3A. Gd3+-chelates of such ligands prove to be useful MRI contrast agents of enhanced relaxivity, greater stability, better clearance, lesser toxicity and higher water solubility.