THERAPEUTIC DRUG MONITORING OF BROAD SPECTRUM ANTIFUNGAL, VORICONAZOLE- A REVIEW

Voriconazole is a broad-spectrum antifungal drug. It belongs to triazole group, and is available in market as oral as well as intravenous (IV) forms. It is highly effective against a number of clinically important fungi causing invasive infections. Its pharmacokinetic profile is non-linear with extensive inter-individual and intra-individual variability. Various factors contribute towards this variability including age, race, gender, genotype, hepatic functions, administration with or without food, and concomitant administration of other drugs causing drug interactions. Variability in plasma concentrations of the drug, arising from these factors, may result in variations in efficacy of the drug or may contribute towards potential toxicity. Voriconazole therapeutic drug monitoring is mandatory considering bad prognosis of patients suffering from invasive fungal infections, especially ones who are immunosuppressed, and prolonged period of treatment needed, in order to optimize antifungal treatment and to prevent the adverse events.&nbsp

Study of erythrocytes as a novel drug carrier for the delivery of artemether

Resealed erythrocytes have been explored in various dimensions of drug delivery, owing to their high biocompatibility and inability to initiate immune response. The present research was designed to evaluate the drug delivery potential of erythrocytes by loading a hydrophobic anti-malarial drug, Artemether. Three different loading techniques were applied to achieve maximum optimized drug loading. A HPLC method was validated for drug quantification in erythrocytes. The relatively high loading was achieved using hypotonic treatment was 31.39% as compared to other two methods. These, drug loaded erythrocytes were characterized for membrane integrity via ESR showing higher ESR values for drug loaded cells as compared to normal cells. Moreover, microscopic evaluation was done to observe morphological changes in erythrocytes after successful loading which showed swollen cells with slight rough surface as compared to smooth surface of normal cells. Drug release was studied for 8 h which showed more than 80% release within 3-7 h from erythrocytes treated with different hypotonic methods. Overall, the study revealed a potential application of erythrocytes in delivery of hydrophobic drugs using hypotonic treatment as compared to other methods

Validated RP-HPLC method for the simultaneous determination of glucosamine sulphate and curcumin in cream formulation: A novel stability-indicating study

Purpose: To develop and validate a stability-indicating reverse phase-high performance liquid chromatography (RP-HPLC) method for the simultaneous determination of glucosamine sulphate (GS) and curcumin (Cur) in drug solution and formulation.Methods: The optimized chromatographic conditions were achieved by passing various compositions of mobile phases over  different reverse phase chromatographic columns. Various validation parameters, including linearity, range, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, specificity and system suitability were performed and evaluated. Stability studies under stressed conditions were done to evaluate the effects of acid, alkali, oxidation, heat and degradation by UV light.Results: The validated method was linear over the concentration range of 0.094 to 1.5 mg/mL for GS and 0.125 to 1.5 mg/mL for Cur, with a correlation coefficient > 0.999. The Intra and inter-day precision were 1.9 % for GS and 0.5 % for Cur, while accuracy was 96 and 102 % for GS and Cur, respectively. Stability studies showed that GS was highly sensitive to acid, alkali and oxidation and less sensitive to heat and UV. Cur was stable against acid, heat and oxidation but sensitive to alkali and UV.Conclusion: The developed and validated method was precise and accurate for both GS and Cur and can potentially be utilized for their identification and quantification at industrial, research and quality control laboratories

Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies

From MDPI via Jisc Publications RouterHistory: accepted 2021-11-14, pub-electronic 2021-11-19Publication status: PublishedFunder: The Oman Research Council; Grant(s): BFP/RGP/HSS/19/198The rapidly growing global burden of cancer poses a major challenge to public health and demands a robust approach to access promising anticancer therapeutics. In parallel, nanotechnology approaches with various pharmacological properties offer efficacious clinical outcomes. The use of new artificial variants of nanosponges (NS) as a transporter of chemotherapeutic drugs to target cells has emerged as a very promising tool. Therefore, in this research, ethylcellulose (EC) NS were prepared using the ultrasonication assisted-emulsion solvent evaporation technique. Withaferin-A (WFA), an active ingredient in Withania somnifera, has been implanted into the nanospongic framework with enhanced anticancer properties. Inside the polymeric structure, WFA was efficiently entrapped (85 ± 11%). The drug (WFA) was found to be stable within polymeric nanosponges, as demonstrated by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies. The WFA-NS had a diameter of 117 ± 4 nm and zeta potential of −39.02 ± 5.71 mV with a polydispersity index (PDI) of 0.419 ± 0.073. In addition, scanning electron microscopy (SEM) revealed the porous surface texture of WFA-NS. In vitro anticancer activity (SRB assay) results showed that WFA–NS exhibited almost twice the anticancer efficacy against MCF-7 cells (IC50 = 1.57 ± 0.091 µM), as quantified by flow cytometry and comet tests. Moreover, fluorescence microscopy with DAPI staining and analysis of DNA fragmentation revealed apoptosis as a mechanism of cancer cell death. The anticancer activity of WFA-NS was further determined in vivo and results were compared to cisplatin. The anticancer activity of WFA-NS was further investigated in vivo, and the data were consistent to those obtained with cisplatin. At Day 10, WFA-NS (10 mg/kg) significantly reduced tumour volume to 72 ± 6%, which was comparable to cisplatin (10 mg/kg), which reduced tumour volume to 78 ± 8%. Finally, the outcomes of molecular modeling (in silico) also suggested that WFA established a stable connection with nanosponges, generating persistent hydrophobic contacts (polar and nonpolar) and helping with the attractive delayed-release features of the formulation. Collectively, all the findings support the use of WFA in nanosponges as a prototype for cancer treatment, and opened up new avenues for increasing the efficacy of natural product-derived medications

Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan

INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research

Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan.

INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500 cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research

Diagnosis of Acute Dengue Virus Infection Using Enzyme-Linked Immunosorbent Assay and Real-Time PCR

Dengue fever is a viral infection caused by the dengue virus and is a growing concern for public health worldwide, particularly in tropical and subtropical regions. This study aimed to assess the diagnostic accuracy of a commercially available NS1 ELISA kit for dengue fever in Pakistan using multiplex qRT-PCR as the gold standard. The study recruited 1236 suspected cases of dengue fever admitted to public sector hospitals in Lahore, Pakistan. Of the suspected cases, 610 (49.3%) were confirmed positive for DENV infection through qRT-PCR, with all four serotypes detected. DENV-2 was the most prevalent serotype, detected in 95.7% of cases. The NS1 ELISA kit detected 71.1% of the positive cases. However, the diagnostic accuracy of the NS1 ELISA kit was found to be only 64.89%. Of the 610 confirmed cases, 68% were male and 32% were female, with a median age of 30 years. Dengue fever was diagnosed in 91.8% of cases, while 8.2% were diagnosed with dengue hemorrhagic fever (DHF). DHF patients had a higher prevalence of abdominal pain, hemorrhagic manifestations, and thrombocytopenia. The cocirculation of all four DENV serotypes in Lahore is concerning and could lead to more severe forms of the disease, such as DHF or dengue shock syndrome, in the future. The study highlights the low diagnostic accuracy of commercially available NS1 ELISA kits and emphasizes the importance of using molecular methods to confirm acute dengue infections. Given the increasing prevalence of dengue fever in developing countries like Pakistan, more accurate and reliable diagnostic tools are needed for effective disease management and control

Piper nigrum Fruit Extract as an Antibiotic Resistance Reversal Agent in MDR Bacteria

Antibiotic resistance development and spread in clinical pathogens is an immense threat that has already outpaced the discovery and development of novel and more effective antibiotic drugs. Recently the focus has been shifted to medicinal plants as novel therapeutic options for reversing antibiotic resistance by targeting different resistance mechanisms. Piper nigrum is a plant that has the potential to reverse antibiotic resistance and increase the efficacy of the current drugs. In the present study, seven different antibiotics, clindamycin, gentamicin, levofloxacin, amikacin, tigecycline, imipenem, and tetracycline, were used against antibiotic-resistant Staphylococcus aureus and Salmonella typhi. Antibiotic resistance reversal analysis was tested by the AST disc method. Increased zones of inhibition of S. aureus by four antibiotics, clindamycin (9 mm), gentamicin (7 mm), levofloxacin (9 mm), and amikacin (9 mm) were recorded after using P. nigrum extract. In addition, the use of P. nigrum extract also increased the zone of inhibition of S. typhi with amikacin (11 mm), gentamicin (10 mm), tigecycline (9 mm), levofloxacin (11 mm), and imipenem (10 mm). This study suggests that P. nigrum extracts can be used as natural antibiotic resistance reversal agents that increase the effectiveness of current antibiotics and can reverse antibiotic resistance

<i>Piper nigrum</i> Fruit Extract as an Antibiotic Resistance Reversal Agent in MDR Bacteria

Antibiotic resistance development and spread in clinical pathogens is an immense threat that has already outpaced the discovery and development of novel and more effective antibiotic drugs. Recently the focus has been shifted to medicinal plants as novel therapeutic options for reversing antibiotic resistance by targeting different resistance mechanisms. Piper nigrum is a plant that has the potential to reverse antibiotic resistance and increase the efficacy of the current drugs. In the present study, seven different antibiotics, clindamycin, gentamicin, levofloxacin, amikacin, tigecycline, imipenem, and tetracycline, were used against antibiotic-resistant Staphylococcus aureus and Salmonella typhi. Antibiotic resistance reversal analysis was tested by the AST disc method. Increased zones of inhibition of S. aureus by four antibiotics, clindamycin (9 mm), gentamicin (7 mm), levofloxacin (9 mm), and amikacin (9 mm) were recorded after using P. nigrum extract. In addition, the use of P. nigrum extract also increased the zone of inhibition of S. typhi with amikacin (11 mm), gentamicin (10 mm), tigecycline (9 mm), levofloxacin (11 mm), and imipenem (10 mm). This study suggests that P. nigrum extracts can be used as natural antibiotic resistance reversal agents that increase the effectiveness of current antibiotics and can reverse antibiotic resistance

Hepatoprotective and Renoprotective Properties of Lovastatin-Loaded Ginger and Garlic Oil Nanoemulsomes: Insights into Serum Biological Parameters

Background and Objectives: Dyslipidemia is gaining much attention among healthcare professionals because of its high association with the malfunctioning of a number of normal physiological and metabolic processes in the body. Obesity is directly interconnected with dyslipidemia and is said to be a denouement of hyperlipidemia and, if left untreated, may lead to intense damage to organs that are directly involved in fat metabolism. The objective of this study was to investigate the synergistic antiobesity and anti-hyperlipidemic activities along with hepato- and renoprotective potential of nanoemulsomes (NES) of lovastatin (LTN)-loaded ginger (GR) and garlic (GL) oils. Materials and Methods: LTN nanoemulsomes co-encapsulated with GR oil and GL oil were prepared by a thin hydration technique. Eight-week-old male Wistar rats weighing 200&ndash;250 g were induced with hyperlipidemia via a high-fat diet (HFD) comprising 40% beef tallow. Body weight, serum biochemical lipid parameters, and those for liver and kidney functions, serum TC, LDL-C, vLDL-C, HDL-C, TG, atherogenic index (AI), ALT, AFT, ALP, &gamma;-GT, total protein (TP), serum albumin and globulin ratio (A/G), serum creatinine, blood urea nitrogen (BUN) and blood urea, and histopathology of hematoxylin and eosin (H&amp;E) stained liver and kidney sections of all aforementioned groups were examined in the treated animals. Results: Nanoemulsomes of LTN-loaded GR and GL oils provided synergistic effects with LTN, exerted better ameliorative actions in reducing serum TC, LDL-C, vLDL-C, triglycerides, and AI, and improved serum HDL-C levels. Serum ALT, AST, ALP, and &gamma;-GT levels were in the normal range for nanoemulsome groups. H&amp;E stained liver and kidney sections of these animals confirmed better hepatoprotective and renoprotective effects than LTN alone. Serum biochemical parameters for renal functions also claimed to be in the moderate range for nanoemulsome-treated groups. Conclusion: This study demonstrated that nanoemulsomes of LTN-loaded GR and GL oils synergistically provided better antihyperlipidemic, hepatoprotective, and renoprotective effects as compared to LTN alone