Grafting of sulfamethoxazole on acrylic acid−vinyl methyl ketone copolymer using the schiff base reaction−application as a drug delivery system

A series of poly(acrylic acid-co-methylvinylketone–graft–sulfamethoxazole)(AVMDS) species was synthesized for drug carrier applications. The synthesis involved two steps: copolymerization of acrylic acid(AA) with methyl vinyl ketone(MVK) through the free radical route and subsequent grafting of the sulfamethoxazole (SMX) onto the copolymer via the Schiff base reaction of the primary amine of SMX with the carbonyl groups of the MVK units. The structures and properties of the materials were characterized by nuclear magnetic resonance(NMR), X-ray diffraction(XRD), differential scanning calorimetry(DSC), and scanning electronic microscopy (SEM). An in-vitro cytotoxicity test of the drug-carrier systems via MTT assay revealed no significant cytotoxic effect at concentrations up to 100?µg?·?ml^?1. The dynamic release of SMX from these systems through a retro-imidation reaction (inverse Schiff base reaction) was investigated in depth, where the diffusion through the polymer matrix, the enhancement of the water solubility of SMX, the influence of the initial drug concentration, the pH of the medium, and the effect of the degree of swelling of the polymer matrix on the release dynamics were evaluated. The AVMGS4 and AVMGS1 drug carrier systems containing 3.58 and 1.18?wt% of SMX were the best performing systems.     

Multi-stage deep probabilistic prediction for travel demand

Applied Intelligence - Accurate demand prediction is an essential component of any decision support system for smart vehicle dispatching. However, predicting real time demand at the...     

Emperor based resource allocation for D2D communication and QoF based routing over cellular V2X in urban environment (ERA-D2Q)

Wireless Networks - Cellular vehicle-to-everything (C-V2X) communications have elicited significant scrutiny in recent years owing to amenities such as comfort, efficiency, and an enhanced...     

Miscibility enhancement of poly(vinyl chloride)/polystyrene blend: Application to membrane separation of benzene from benzene/cyclohexane mixture by pervaporation

In order to improve the miscibility of poly(vinyl chloride)/polystyrene (PVC/PS) system and to use the prepared material as a membrane to separate benzene from benzene/cyclohexane mixture by pervaporation technique, two poly(styrene-co-N-vinylpyrrolidone) (PSVP) copolymers containing 6.67 and 13.55 mol% of N-vinylpyrrolidone (N-VP) contents were synthesized through a radical polymerization. A comparative study of the miscibility of the PVC/PSVP blends with different compositions was carried out using differential scanning calorimetry, viscosimetry and Fourier transform infrared spectroscopy methods in which the interaction parameters between the two components were widely investigated. To improve the pervaporative flux of PVC membrane to separate benzene from benzene/cyclohexane mixture, a preliminary test of swelling and sorption was performed on PVC/PSVP7 membranes using an azeotropic benzene/cyclohexane mixture. It was revealed that the PVC/PSVP7 membrane containing 10 wt% of PSVP7 showed the best performance and the diffusion behaviour of this mixture through PVC and PVC/PCVP7 membranes has a Fickian behaviour. The pervaporation parameters of this membrane support those of the swelling and selective sorption data and reveal that this membrane could enhance the total flux without significantly affecting its selectivity to benzene.     

Differences in Transporters Rather than Drug Targets Are the Principal Determinants of the Different Innate Sensitivities of Trypanosoma congolense and Trypanozoon Subgenus Trypanosomes to Diamidines and Melaminophenyl Arsenicals

The animal trypanosomiases are infections in a wide range of (domesticated) animals with any species of African trypanosome, such as Trypanosoma brucei, T. evansi, T. congolense, T. equiperdum and T. vivax. Symptoms differ between host and infective species and stage of infection and are treated with a small set of decades-old trypanocides. A complication is that not all trypanosome species are equally sensitive to all drugs and the reasons are at best partially understood. Here, we investigate whether drug transporters, mostly identified in T. b. brucei, determine the different drug sensitivities. We report that homologues of the aminopurine transporter TbAT1 and the aquaporin TbAQP2 are absent in T. congolense, while their introduction greatly sensitises this species to diamidine (pentamidine, diminazene) and melaminophenyl (melarsomine) drugs. Accumulation of these drugs in the transgenic lines was much more rapid. T. congolense is also inherently less sensitive to suramin than T. brucei, despite accumulating it faster. Expression of a proposed suramin transporter, located in T. brucei lysosomes, in T. congolense, did not alter its suramin sensitivity. We conclude that for several of the most important classes of trypanocides the presence of specific transporters, rather than drug targets, is the determining factor of drug efficacy.     

Differential Metabotypes in Synovial Fibroblasts and Synovial Fluid in Hip Osteoarthritis Patients Support Inflammatory Responses

Changes in cellular metabolism have been implicated in mediating the activated fibroblast phenotype in a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim of this study was therefore to characterise the metabolic profile of synovial joint fluid and synovial fibroblasts under both basal and inflammatory conditions in a cohort of obese and normal-weight hip OA patients. Furthermore, we sought to ascertain whether modulation of a metabolic pathway in OA synovial fibroblasts could alter their inflammatory activity. Synovium and synovial fluid was obtained from hip OA patients, who were either of normal-weight or obese and were undergoing elective joint replacement surgery. The synovial fluid metabolome was determined by 1H NMR spectroscopy. The metabolic profile of isolated synovial fibroblasts in vitro was characterised by lactate secretion, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyser. The effects of a small molecule pharmacological inhibitor and siRNA targeted at glutaminase-1 (GLS1) were assessed to probe the role of glutamine metabolism in OA synovial fibroblast function. Obese OA patient synovial fluid (n = 5) exhibited a different metabotype, compared to normal-weight patient fluid (n = 6), with significantly increased levels of 1, 3-dimethylurate, N-Nitrosodimethylamine, succinate, tyrosine, pyruvate, glucose, glycine and lactate, and enrichment of the glutamine–glutamate metabolic pathway, which correlated with increasing adiposity. In vitro, isolated obese OA fibroblasts exhibited greater basal lactate secretion and aerobic glycolysis, and increased mitochondrial respiration when stimulated with pro-inflammatory cytokine TNFα, compared to fibroblasts from normal-weight patients. Inhibition of GLS1 attenuated the TNFα-induced expression and secretion of IL-6 in OA synovial fibroblasts. These findings suggest that altered cellular metabolism underpins the inflammatory phenotype of OA fibroblasts, and that targeted inhibition of glutamine–glutamate metabolism may provide a route to reducing the pathological effects of joint inflammation in OA patients who are obese.     

Miscibility of poly(acrylic acid)/poly(methyl vinyl ketone) blend and in vitro application as drug carrier system

A series of poly(acrylic acid)/poly(methyl vinyl ketone) (PAA/PMVK) blends with different compositions were prepared by the solvent casting method. The miscibility of this pair of polymers was investigated by differential scanning calorimetry(DSC), Fourier transform infra-red (FTIR) and X-Ray diffraction (XRD) techniques. An in-vitro cytotoxicity test of the drug-carrier system via MTT (3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay revealed no significant cytotoxic effects at concentrations up to 100 µg· ml^?1. The STX/PAA-50 drug carrier systems were also prepared by solvent casting of solutions containing the sulfamethoxazole (STX) used as drug model and PAA/PMVK blend in N.N-dimethylformamide then crosslinked with acidified ethylene glycol. The release dynamic of STX from the prepared hydrogels was investigated in which the diffusion through the polymer matrix, the enhancement of the water solubility of STX, the influence of the initial drug concentration, the pH of the medium, and the effect of the degree of swelling of the polymer matrix on the release dynamic was evaluated. According to the total gastrointestinal transit time estimated by Belzer, the estimate distribution of STX released in the different organs indicated that the performance is obtained with the drug – carrier-system containing equal ratios of polymer and 10 wt% of STX (STX-10/PAA-50).