Investigation of 5-fluorouracil cardiotoxicity in combinational therapy: Influence of risk factors and demographics in a Pakistani population.

INTRODUCTION: 5-Fluorouracil (5-FU) is a chemotherapeutic agent used to treat various types of cancers. Although widely used, it has consistently been attributed to cardiotoxicities after administration. The purpose of this study was to assess the parameters and predictors of cardiotoxicities associated with various 5-FU-based chemotherapeutic protocols in patients with GI/colorectal cancer, as well as the correlation of these cardiotoxic events with age, sex, cumulative dose, and risk factors such as obesity, hypertension, and family history of cardiac diseases. METHODS: A prospective study consisting of 396 patients of both sexes was conducted in the oncology ward of Nishtar Hospital in Multan, Pakistan. Patients were grouped according to the therapeutic protocol they received (5-FU monotherapy or in combination, with different dosing regimens). Electrocardiography and serum troponin levels were used to assess 5-FU-induced cardiotoxicity. In cases where cardiotoxicity was detected, 5-FU treatment was interrupted; nitroglycerin, nitrates, and calcium channel blockers were administered; and cardiac monitoring was initiated. 5-FU was discontinued in all cases of acute myocardial infarction. RESULTS: Of the 396 patients, 28.5% reported different cardiotoxic symptoms after receiving various 5-FU-containing protocols. 35% had anginal pain, 13% suffered a myocardial infarction, 11% developed hypertension, and 10% presented heart failure. Patients receiving 5-FU combination therapy showed cardiotoxic events that were significantly different from those on 5-FU monotherapy. Based on the ECG results, only the QTc-d interval increased significantly (p < 0.001) after therapy. 68% of the patients had troponin levels > 2 ng/mL at the end of treatment. CONCLUSIONS: Pre-existing cardiac diseases, treatment duration, smoking, and obesity were found to be influential components in the development of cardiotoxicity, and patients with cancer should be closely monitored during 5-FU chemotherapy.

DEVELOPMENT AND VALIDATION OF FAST REVERSED-PHASE HPLC METHOD FOR ANALYSIS OF ESOMEPRAZOLE IN RABBIT PLASMA.

The present study focused to develop rapid, accurate and sensitive reversed-phase high pressure liquid chromatography method for the quantification of esomeprazole (ESO) magnesium in rabbit plasma. Chromatographic separation was achieved isocratically on a reversed-phase C,, column using simple mobile phase consisting of of methanol : acetonitrile: 0.05 M phosphate buffer, pH 7 adjusted with potassium hydroxide (45 : 10 : 45, v/v/v) at a flow rate of 1.0 mL/min and UV detection at 302 nm. The method was validated for system suitability, linearity, precision, accuracy, stability, robustness, LOD and LOQ. The described method stated good linearity over the range of 0.01 to 2.5 pg/mL (r = 0.999). The extraction recovery of esomeprazole was more than 95.3%. The method was precise with relative standard deviation < 1% with more than 90% accuracy and limit of quantification 0.0309 µg/mL. The freeze thaw stability studies indicated that the rabbit plasma samples containing esomeprazole could be stored in freezer at -20°C and handled under normal laboratory conditions without significant loss of drug. In conclusion, the developed method is simple, cost effective and reproducible, with improved sensitivity and running time of analysis.

APPLICATION OF VARIOUS POLYMERS AND POLYMERS BASED TECHNIQUES USED TO IMPROVE SOLUBILITY OF POORLY WATER SOLUBLE DRUGS: A REVIEW.

Solubility is concerned with solute and solvent to form a homogenous mixture. If solubility of a drug is low, then usually it is difficult to achieve desired therapeutic level of drug. Most of the newly developed entities have solubility problems and encounter difficulty in dissolution. Basic aim of solubility enhancement is to achieve desired therapeutic'level of drug to produce required pharmacological response. Different techniques are being used to enhance the solubility of water insoluble drugs. These techniques include particle size reduction, spray drying, kneading method, solvent evaporation method, salt formation, microemulsions, co-solven- cy, hydrosols, prodrug approach, supercritical fluid process, hydrogel micro particles etc. Selection of solubility improving method depends on drug properties, site of absorption, and required dosage form characteristics. Variety of polymers are also used to enhance solubility of these drugs like polyethylene glycol 300, polyvinyl pyrrolidone, chitosan, ß-cyclodextrins etc.

FABRICATION AND IN VITRO EVALUATION OF 5-FLOROURACIL LOADED CHONDROITIN SULFATE-SODIUM ALGINATE MICROSPHERES FOR COLON SPECIFIC DELIVERY.

Chondroitin sulfate and sodium alginate were incorporated in different ratios to prepare glutaraldehyde (GA) crosslinked microspheres by water-in-oil emulsion crosslinking method for delivery of 5-flurouracil (5-FU) to colon. Chemical interaction, surface morphology, thermal degradability, crystallinity evaluation, elemental analysis and drug release results were computed by using FTIR, SEM, DSC and TGA, PXRD, EXD and dissolution studies at pH 1.2, pH 6.8 and pH 7.4, respectively. Results revealed an acetal ring formation, non-porous surfaces, stability up to 450 degrees C with mass loss of 84.31%, variation in carbon and oxygen contents and targeted release at pH 7.4. Different kinetic models were applied on release studies i.e., zero order, first order, Higuchi and Korsmeyer-Peppas. Higuchi model was declared as best fit model based on r2 value (0.99) and mechanism of release was non-Fickian diffusion. A potential approach for colonic delivery of 5-FU was successfully developed.

PREPARATION AND EVALUATION OF pH RESPONSIVE POLY(2-HYDROXYETHYL METHACRYLATE-CO-ITACONIC ACID) MICROGELS FOR CONTROLLED DRUG DELIVERY.

In this study, a series of pH sensitive microgels (MGs) were prepared by modified free radical suspension polymerization of 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA), using ethylene glycol dimethacrylate (EGDMA) as crosslinker. Equilibrium swelling technique was employed for esomeprazole magnesium trihydrate (EMT) loading. Prepared microgels were characterized through Fourier transforms infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), dynamic light scattering technique (DLS), scanning electron microscopy (SEM), equilibrium swelling and in vitro drug release kinetics. FTIR and TGA confirmed the formation of copolymeric p(HEMA-co-IA) network. SEM and DLS revealed smooth, round and uniformly distributed microspheres with particle size up to 10 µm. Developed microgels found to be pH responsive in nature. All the formulations (HIDI - HID5) followed Higuchi model with non-Fickian diffusion mechanism of drug release. It was concluded that p(HEMA-co-IA) microgels have potential to be used as drug carriers for site specific and controlled drug delivery.

Green Synthesis and Evaluation of Lepidium didymum-mediated Silver Nanoparticles for in vitro Antibacterial Activity and Wound Healing in the Animal Model.

Wounds serve as an appropriate medium for the growth of pathogenic bacteria, and bacterial resistance to already available antibiotics demands new and safe approaches in the field of medicine. Silver nanoparticles (AgNPs) exhibited a wide range of applications in biomedicine and emerged as promising nano-antibiotics. The biological preparation of AgNPs by utilizing aqueous plant extract has become an encouraging alternative to traditional chemical methodologies, owing to a viable eco-friendly approach. In the present study, Lepidium didymum leaves extract was used for the biosynthesis of AgNPs-LD. The nanoparticles were characterized through UV-Vis spectroscopy, Fourier transforms infrared spectrometry (FTIR), Scanning electron microscopy (SEM), and X-ray diffraction (XRD). The antibacterial activity of AgNPs-LD was evaluated against Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. Further, AgNPs-LD nanoparticles were incorporated into topical gels to evaluate their effectiveness for wound healing in the rat model. UV-visible spectra showed a surface resonance peak around 400 nm correlated with the synthesis of AgNPs; FTIR spectra verified the participation of phytochemicals present in L. didymum leaves extract in AgNPs-LD synthesis; and SEM revealed dispersed spherical nanoparticles as well as aggregated clusters. XRD analysis confirmed the crystalline nature, face-centered cubic lattice, and average crystallite size of 21.42 nm. The AgNPs-LD showed promising antibacterial activity against tested strains with a maximum zone of inhibition against P. aeruginosa and showed accelerated wound healing capacity comparable to control and standard treatments over the time course of wound healing. The current study concluded that biosynthesized AgNPs-LD nanoparticles are effective as antibacterial agents and are promising novel wound healing products for clinical applications.

Prevalence of nasal Staphylococcus aureus and methicillin-resistant Staphylococcus aureus in hospital personnel and associated risk factors.

Hospital- and community-acquired Staphylococcus aureus infections pose a substantial burden in terms of morbidity, mortality and healthcare costs. The extent of nosocomial S. aureus transmission, in particular methicillin-resistant S. aureus (MRSA), the prevalence of S. aureus colonization in healthy personnel working in hospital was determined. Factors associated with S. aureus nasal carriage and antibiotic sensitivity pattern of the isolates were also analyzed. A total of 129 nasal swabs and epidemiological information concerning risk factors for nasal carriage were obtained from physicians, nurses, sanitary workers and administrative staff. Antibiotic susceptibility testing was performed using disk diffusion method. The prevalence of S. aureus and MRSA nasal carriage was significantly (p < 0.05) higher in physicians (51.8%, 18.5%), nurses (66.6%, 27.3%) and sanitary workers (59%, 13.6%) as compared to administrative staff (27.6%, 2.1%). There was no association between smoking and nasal S. aureus carriage (p = 0.006) and the isolates from physician. The nurses and sanitary workers were comparatively more resistant to various antibiotics than the isolates from administrative staff.

Nasal carriage of staphylococci in health care workers: antimicrobial susceptibility profile.

One year prospective study was evaluated to ascertain the prevalence of nasal carriage of potentially pathogenic bacteria in health care workers and the antibiotic susceptibility profile. The bacterial strains were identified by conventional method and the antibiotic resistance was carried out by disc diffusion method. The prevalence of Staphylococcus aureus, coagulase negative staphylococci and methicillin resistant Staphylococcus aureus were 48%, 46% and 14% respectively. The antibiotic susceptibility pattern of these isolates revealed that Staphylococcus aureus were more resistant towards antibiotics than coagulase negative staphylococci. The most effective antibiotic for S. aureus was found to be vancomycin with 100% efficacy, then cephalothin 92%, ciprofloxacin 91%, amikacin 77% and erythromycin 55%, ampicillin 11% and penicillin 3%. Coagulase negative staphylococci were 100% sensitive to vancomycin and cephalothin. Oxacillin showed 78% effectiveness; while ampicillin and penicillin, demonstrated 64% and 59% respectively. Doxycycline (93%), amikacin (93%), fusidic acid (90%) and erythromycin (92%) were effective antimicrobials.