Abstract Poor aqueous solubility of eplerenone (EPL) is a major obstacle to achieve sufficient bi... more Abstract Poor aqueous solubility of eplerenone (EPL) is a major obstacle to achieve sufficient bioavailability after oral administration. In this study, we aimed to develop and evaluate eplerenone nanocrystals (EPL-NCs) for solubility and dissolution enhancement. D-optimal combined mixture process using Design-Expert software was employed to generate different combinations for optimization. EPL-NCs were prepared by a bottom-up, controlled crystallization technique during freeze-drying. The optimized EPL-NCs were evaluated for their size, morphology, thermal behavior, crystalline structure, saturation solubility, dissolution profile, in vivo pharmacokinetics, and acute toxicity. The optimized EPL-NCs showed mean particle size of 46.8 nm. Scanning electron microscopy revealed the formation of elongated parallelepiped shaped NCs. DSC and PXRD analysis confirmed the crystalline structure and the absence of any polymorphic transition in EPL-NCs. Furthermore, EPL-NCs demonstrated a 17-fold prompt increase in the saturation solubility of EPL (8.96 vs. 155.85 µg/mL). The dissolution rate was also significantly higher as indicated by ∼95% dissolution from EPL-NCs in 10 min compared to only 29% from EPL powder. EPL-NCs improved the oral bioavailability as indicated by higher AUC, C max, and lower T max than EPL powder. Acute oral toxicity study showed that EPL-NCs do not pose any toxicity concern to the blood and vital organs. Consequently, NCs prepared by controlled crystallization technique present a promising strategy to improve solubility profile, dissolution velocity and bioavailability of poorly water-soluble drugs.
BACKGROUND Ajuga bracteosa is a traditional herb used against various diseases. OBJECTIVE Current... more BACKGROUND Ajuga bracteosa is a traditional herb used against various diseases. OBJECTIVE Current research aimed to investigate the anti-diabetic and hepato-protective effect of green synthesized silver nanoparticles (ABAgNPs) using Ajuga bracteosa aqueous extract (ABaqu). METHODS In vitro anti-diabetic and cytotoxic effects were carried out via α- glucosidase inhibition, brine shrimp lethality, and protein kinase inhibition assays. For in vivo screening of 200 mg/kg and 400 mg/kg of both ABAgNPs and ABaqu in alloxan-induced and CCl4-induced Swiss albino mice were used. Liver and kidney functional markers, hematology, and histopathological studies were carried out after 14 days of administration. RESULTS In vivo antidiabetic and anti-cancerous effects showed valuable anti-hyperglycemic and hepato-protective potential when mice were treated with ABaqu and ABAgNPs. A significant reduction in the blood glucose level was recorded when ABaqu and ABAgNPs were administrated orally compared...
Mental retardation, also termed as learning impairment or cognitive dysfunction, is a serious man... more Mental retardation, also termed as learning impairment or cognitive dysfunction, is a serious manifestation of nervous system. The defining features of mental retardation are low or subaverage intellectual functioning (Intelligence quotient<70), impairment in at least two of the adaptive skills (e.g communication ability, self care, self guidance, reading, writing ability, etc) before 18 year of age1. Molecular cytogenetics is the study of genetic disorders using advanced technologies combined with cytogenetic and molecular methodologies2. Molecular diagnosis has equal importance as clinical diagnosis in mental retardation and day by day new advancement in these methodologies are being introduced by molecular cytogeneticists. The promising achievement of molecular cytogenetic techniques is the genetic counseling of high risk pregnancies. The current mini-survey of literature discusses an overview of these techniques employed to investigate deletion, duplication, inversion and tra...
BACKGROUND XPD Lys751Gln polymorphism may modulate inter-individual variation in repair capacity ... more BACKGROUND XPD Lys751Gln polymorphism may modulate inter-individual variation in repair capacity of DNA, which may enhance a person's susceptibility to develop colorectal cancer (CRC). The analysis of XPD Lys751Gln polymorphism may provide important information for identifying high-risk individuals and for selecting the most appropriate treatment for poor prognostic CRC patients. OBJECTIVE The overall objective was to find out the association of XPD Lys751Gln gene polymorphism with the risk of having a colorectal cancer and the ultimate clinical outcomes. In this study a total of 300 subjects (CRC and Controls), were genotyped for XPD Lys751Gln. METHODS Using PCR-RFLP methods, the association of XPD Lys751Gln gene polymorphism with the risk of having a colorectal cancer was studied. In addition to overall risk assessment, genotyping results were also investigated with respect to the lifestyle risk factors, patients treated with oxaliplatin-based chemotherapy and clinicopathological characteristics. RESULTS The overall correlation between the XPD Lys751Gln genetic variation and the CRC risk was observed to be significant with both the homozygous variant genotype Gln/Gln as well as heterozygous genotype Lys/Gln being associated with the increased risk of CRC. Additional stratified analyses revealed that XPD Lys751Gln variants remarkably increased risk of CRC in males and younger individuals (≤ 50 years), Naswar users (8.09-fold) and high intake of red meat. CONCLUSIONS Our findings suggest that the relationship between the XPD Lys751Gln variants and lifestyle factors modulates the risk for CRC in Pakistani population.
As the founding editor, it is my privilege and indeed an honour to write this inaugural editorial... more As the founding editor, it is my privilege and indeed an honour to write this inaugural editorial on the launch of the Pakistan Journal of Nuclear Medicine (PJNM), the official journal of the Pakistan Society of Nuclear Medicine and the first nuclear medicine journal being published from Pakistan. PJNM aspires to represent the professional excellence and contributions of the nuclear medicine community in Pakistan at an international level. This peer-reviewed journal aims to contribute towards research and education of physicians in the field of nuclear medicine and allied sciences. The journal shall provide a platform
Background: Multi-drug resistance in bacterial pathogens is a rising concern today. Green synthes... more Background: Multi-drug resistance in bacterial pathogens is a rising concern today. Green synthesis technology has been utilized to cure infectious diseases. Objectives: The aim of the current research was to highlight the antibacterial, antioxidant, and phytochemical screening of green synthesized silver nanoparticles using Ajuga bracteosa. Methods: Extract of A. bracteosa was prepared by maceration technique. Silver nanoparticles were synthesized using A. bracteosa extract and were confirmed by UV-vis spectrophotometer, Scanning electron microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The antibacterial, anti-biofilm, cell proliferation inhibition, TLC-Bioautography, TLC-Spot screening, antioxidant, and phytochemical screening were also investigated. Results: UV-viz spectrum and Scanning electron microscopy indicated the synthesis of green nanoparticles at 400 nm with tube like structures. FTIR spectrum showed the functional groups have a role in capping and st...
Nanocarriers endow tremendous benefits to the drug delivery systems depending upon the specific p... more Nanocarriers endow tremendous benefits to the drug delivery systems depending upon the specific properties of either component. These benefits include, increase in the drug blood retention time, reduced efflux, additional toxicity and targeted delivery. Methotrexate (MTX) is clinically used for cancer treatment. Higher dosage of MTX results in hepatic and renal toxicity. In this study methotrexate silver nanoparticles (Ag-MTX) coated with polyethylene glycol (PEG) are synthesized and characterized. Their anticancer activity and biocompatibility is also evaluated. Ag-MTX nanoparticles are synthesized by chemical reduction method. They are characterized by Ultraviolet-Visible Spectroscopy and Fourier Transform Infrared Spectroscopy. Average size of PEG coated Ag-MTX nanoparticles (PEG-Ag-MTX nanoparticles) is 12nm. These particles exhibited improved anticancer activity against MCF-7 cell line. Hemolytic activity of these particles was significantly less than MTX. PEG-Ag-MTX nanoparticles are potential nanocarrier of methotrexate which may offer MTX based cancer treatment with reduced side effects. In-vivo investigations should be carried out to explore them in detail.
Typhoid is a major health problem but conventional diagnostic methods are inadequate.OBJECTIVES: ... more Typhoid is a major health problem but conventional diagnostic methods are inadequate.OBJECTIVES: Comparison of two latest diagnostic techniques, PCR and Typhidot. SUBJECT& METHODS: Blood samples from 20 patients of suspected early ...
A simple and selective capillary electrophoretic method was established for the simultaneous dete... more A simple and selective capillary electrophoretic method was established for the simultaneous determination of methotrexate (MTX), 7-hydroxymethotrexate (7-OHMTX), 2,4-diamino-N10-methylpteroic acid (DAMPA), and polyglutamate derivatives [MTX-(Glu)n, n=2-7] in whole blood. After extraction, those analytes were separated by fused-silica capillary and a running buffer containing glycine (1.2 M, pH 9.3). The quantitative ranges were 10-50 microM for each analyte. The intra- and inter-day RSD and RE values were all less than 6 and 11%, respectively. The limits of detection (S/N= 3, injection 5 s) were found to be 1 microM for MTX, 7-OHMTX, MTX-(Glu)2, MTX-(Glu)3, and MTX-(Glu)4; 3 microM for MTX-(Glu)5 and MTX-(Glu)6; 5 microM for MTX-(Glu)7, and 8 microM for DAMPA. All recoveries were greater than 94%. This method was applied to blood MTX monitoring in a patient with acute lymphoblastic leukemia.
International Journal of Polymeric Materials and Polymeric Biomaterials
ABSTRACT Sorafenib is the only approved targeted agent against hepatocellular carcinoma (HCC). It... more ABSTRACT Sorafenib is the only approved targeted agent against hepatocellular carcinoma (HCC). It has several limitations predominantly poor aqueous solubility and hepatic first-pass effect that limits its oral delivery leading to low bioavailability, large inter-subject variability, narrow therapeutic window and side effects. Tosylate is used to improve its solubility, which is practically insoluble in water (60 µg/mL) so problems with sorafenib solubility persist. To improve the paharmacokinetic profile, minimize the side effects, and targeting drug to the tumor tissues, several polymeric nano-formulations are being evaluated. In this comprehensive review, various reported polymeric nano-delivery systems for sorafenib are comprehensively covered. GRAPHICAL ABSTRACT
Methotrexate (MTX) is a well-known chemotherapeutic agent for solid tumor. However, its clinical ... more Methotrexate (MTX) is a well-known chemotherapeutic agent for solid tumor. However, its clinical usage is limited due to low permeability, cellular drug efflux, and non-specific drug delivery. These constraints require dose dumping and result in dose-dependent toxic effects. In the current study, MTX-loaded PEGylated gold nanoparticles (PEG-MTX-AuNPs) exposed to acidic pH (tumor cell) trigger a significant drug release profile. MTX was conjugated to citrate functionalized AuNP and stabilized by thiolated methyl polyethylene glycol (mPEG-SH). PEG-MTX-AuNP was cationic with 39.5 ± 1.2 mV zeta potential and a particle size of 39 nm, as revealed by DLS and TEM. AuNP size ranging from 40 to 50 nm was favorable for maximum endosomal uptake and fast drug release. MTX-AuNP showed 39.4% (22.28 µg/ml) drug loading efficiency. Spectroscopic examinations confirmed MTX chemisorption onto AuNPs via carboxyl (–COOH) and gold dative bond. In vitro release study indicated a 6.5-fold increased MTX release in the acidic environment (pH 4.5) compared to physiological pH. The terminal mPEG provided stability in a biological medium, refrained from protein deactivation, and exhibited significant hemocompatibility (less than 5% hemolysis up to 10 μM concentration). In vitro cytotoxicity against human rhabdomyosarcoma (RD) cells indicated significant (p < 0.0001) anticancer activity of PEG-MTX-AuNPs with low median growth inhibition concentration (GI50 = 3.61 ± 0.94 μM) compared to MTX (13.12 ± 0.98 μM) and AuNPs (5.24 ± 0.98 μM) alone. In conclusion, PEG-MTX-AuNPs offer higher stability in ionic and biological media, hemocompatibility, and acidic pH-dependent MTX release, and mediate enhanced in vitro anticancer activity that makes them a potential candidate for skeletal muscle sarcomas. Methotrexate (MTX) is a weak dicarboxylic acid which become ionized at pH 7.4 (PBS) and unionized at endosomal pH 4.5. In ionized state MTX exchanges the negatively charged citrate ions and chemisorbed on AuNPs surface to stabilize and cap AuNPs. While in acidic media MTX become unionized and released in media. The enhanced intracellular release improves therapeutic outcome of MTX. The chemisorption of MTX was further confirmed with FTIR, supported by XRD and UV results.Scheme 1 Methotrexate binding mechanism to AuNP surface Methotrexate binding mechanism to AuNP surface
Current pharmaceutical biotechnology, Jan 17, 2018
Many health hazardous diseases are caused by clinical pathogens. Drug-resistant microbes are one ... more Many health hazardous diseases are caused by clinical pathogens. Drug-resistant microbes are one of the major health problems in the world. To overcome the effect of infectious diseases new antimicrobial agent from nature has been explored which is environmentally friendly, less costly and more effective for the development of next-generation drugs. Bergenia ciliata and silver nitrate both have medicinal properties. The aim of the current research was to evaluate the cytotoxic, and antibacterial effect of green synthesized nanoparticles using Bergenia ciliata rhizome against clinical bacterial pathogens. Extract of Bergenia ciliata was prepared by maceration technique. Silver nanoparticles were synthesized using Bergenia ciliata rhizome extract. Synthesized silver nanoparticles were confirmed by UV-vis spectrophotometer, Scanning electron microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The antibacterial, anti-biofilm, cell proliferation inhibition, DNA protectio...
Tailoring personalized cancer nanomedicines demands detailed understanding of the tumor microenvi... more Tailoring personalized cancer nanomedicines demands detailed understanding of the tumor microenvironment. In recent years, smart upconversion nanoparticles with the ability to exploit the unique characteristics of the tumor microenvironment for precise targeting have been designed. To activate upconversion nanoparticles, various bio-physicochemical characteristics of the tumor microenvironment, namely, acidic pH, redox reactants, and hypoxia, are exploited. Stimuli-responsive upconversion nanoparticles also utilize the excessive presence of adenosine triphosphate (ATP), riboflavin, and Zn2+ in tumors. An overview of the design of stimulus-responsive upconversion nanoparticles that precisely target and respond to tumors via targeting the tumor microenvironment and intracellular signals is provided. Detailed understanding of the tumor microenvironment and the personalized design of upconversion nanoparticles will result in more effective clinical translation.
This study was aimed to develop doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan ... more This study was aimed to develop doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan (DOX-GCPQ) nanoformulation that could enable DOX delivery and noninvasive monitoring of drug accumulation and biodistribution at tumor site utilizing selfflorescent property of doxorubicin. Materials and methods: DOX-GCPQ amphiphilic polymeric nanoformulations were prepared and optimized using artificial neural network (ANN) and characterized for surface morphology by atomic force microscopy, particle size with polydispersity index (PDI), and zeta potential by dynamic light scattering. Fourier transformed infrared (FTIR) and X-ray diffractometer studies were performed to examine drug polymer interaction. The ANN-optimized nanoformulation was investigated for in vitro release, cellular, tumor, and tissue uptake. Results: The optimized DOX-GCPQ nanoformulation was anionic spherical micelles with the hydrodynamic particle size of 97.8±1.5 nm, the PDI of ,0.3, the zeta potential of 28±2 mV, and the encapsulation efficiency of 80%±1.5%. Nanoformulation demonstrated a sustained release pattern over 48 h, assuming Weibull model. Fluorescence microscopy revealed higher uptake of DOX-GCPQ in human rhabdomyosarcoma (RD) cells as compared to free DOX. In vitro cytotoxicity assay indicated a significant cytotoxicity of DOX-GCPQ against RD cells as compared to DOX and blank GCPQ (P,0.05). DOX-GCPQ exhibited low IC 50 (1.7±0.404 µmol) when compared to that of DOX (3.0±0.968 µmol). In skin tumor xenografts, optical imaging revealed significantly lower DOX-GCPQ in heart and liver (P,0.05) and accumulated mainly in tumor (P,0.05) as compared to other tissues. Conclusion: The features of nanoformulation, ie, small particle size, sustained drug release, and enhanced cellular uptake, potential to target tumor passively coupled with the possibility of monitoring of tumor localization by optical imaging may make DOX-GCPQ an efficient nanotheranostic system.
A regulated immune system employs multiple cell types, diverse variety of cytokines and interacti... more A regulated immune system employs multiple cell types, diverse variety of cytokines and interacting signalling networks against infections. Systems biology offers a promising solution to model and simulate such large populations of interacting components of immune systems holistically. This study focuses on the distinct components of the adaptive immune system and analysis, both individually and in association with HCV infection. The effective and failed adaptive immune response models have been developed followed by interventions/perturbations of various treatment strategies to get better assessment of the treatment responses under varying stimuli. Based on the model predictions, the NK cells, T regulatory cells, IL-10, IL-21, IL-12, IL-2 entities are found to be the most critical determinants of treatment response. The proposed potential immunomodulatory therapeutic interventions include IL-21 treatment, blocking of inhibitory receptors on T-cells and exogenous anti-IL-10 antibody...
Background: Hepatitis C virus (HCV) is a major cause of chronic liver infection, which may lead t... more Background: Hepatitis C virus (HCV) is a major cause of chronic liver infection, which may lead to liver cirrhosis, fibrosis, and hepatocellular carcinoma while about one-fourth of the infected patients recover spontaneously. The host immune response remains decisive in the outcomes of antiviral treatment. Single nucleotide polymorphisms (SNPs) at the genes within the human leukocyte antigen (HLA) cluster are associated with differential immune response and treatment outcomes. Objectives: This study aimed to determine the association of SNPs in Tumor necrosis factor-alpha (TNF-α) and HLA genes (HLA-DRB1 and HLA-DQB1) with the outcomes of HCV infection and anti-HCV therapy. Methods: The study included 245 HCV-infected patients visiting a tertiary care hospital, located in Islamabad, Pakistan. Viral quantification and genotyping were performed by real-time PCR. Twenty SNPs in TNF-α, HLA-DRB1, and HLA-DQB1 were sequence-genotyped by the Sanger method in 180 patients. Multivariate logistic regression was performed to establish the association of SNPs with spontaneous clearance of the virus and response to anti-HCV therapy. Results: Five out of 20 SNPs were novel. Allelic variants at three different locations (HLA-DRB1, rs2308802; HLA-DQB1,-8447, and HLA-DQB1,-8471) showed significant associations with two groups of HCV patients receiving anti-HCV treatment (responsive and nonresponsive). Multivariate analyses disclosed that genotype A/A at HLA-DQB1 (-8471) was a significant predictor of positive response to treatment although in the presence of the variant at HLA-DRB1 (rs230880) (P = 0.004). However, no association was detected between the haplotypes constructed for the three sets of SNPs and different categories of patients. Conclusions: This study established a novel SNP HLA-DQB1(-8471) as an important predictor of an effective response to anti-HCV therapy in HCV-infected Pakistani patients. Prescreening of this variant before therapy would benefit HCV patients.
Approximately 10 million people in Pakistan are infected with the hepatitis C virus (HCV). Most p... more Approximately 10 million people in Pakistan are infected with the hepatitis C virus (HCV). Most patients develop chronic hepatitis, with rare cases of spontaneous clearance. However, little is known about multidrug resistant viral variants in Pakistan. This case study describes a 47-year-old male diagnosed with chronic HCV genotype 3a infection in 2003. After an initial diagnosis of viral infection, the patient remained treatment naïve for 5 years. He received two therapy cycles of interferon (IFN) plus ribavirin (RBV) in 2007 and 2010, however, he was non-responsive to the therapy. The patient then received an additional two treatment cycles of pegylated IFN α-2b plus RBV (in 2011 and 2013); he was still non-responsive. In 2016, the patient underwent sofosbuvir plus RBV combination therapy, however, the sustained virological response was still not achieved. The host genetic factor was found to be heterozygous guanine and thymine (GT) and cytosine and thymine (CT) genotypes of rs809...
Abstract Poor aqueous solubility of eplerenone (EPL) is a major obstacle to achieve sufficient bi... more Abstract Poor aqueous solubility of eplerenone (EPL) is a major obstacle to achieve sufficient bioavailability after oral administration. In this study, we aimed to develop and evaluate eplerenone nanocrystals (EPL-NCs) for solubility and dissolution enhancement. D-optimal combined mixture process using Design-Expert software was employed to generate different combinations for optimization. EPL-NCs were prepared by a bottom-up, controlled crystallization technique during freeze-drying. The optimized EPL-NCs were evaluated for their size, morphology, thermal behavior, crystalline structure, saturation solubility, dissolution profile, in vivo pharmacokinetics, and acute toxicity. The optimized EPL-NCs showed mean particle size of 46.8 nm. Scanning electron microscopy revealed the formation of elongated parallelepiped shaped NCs. DSC and PXRD analysis confirmed the crystalline structure and the absence of any polymorphic transition in EPL-NCs. Furthermore, EPL-NCs demonstrated a 17-fold prompt increase in the saturation solubility of EPL (8.96 vs. 155.85 µg/mL). The dissolution rate was also significantly higher as indicated by ∼95% dissolution from EPL-NCs in 10 min compared to only 29% from EPL powder. EPL-NCs improved the oral bioavailability as indicated by higher AUC, C max, and lower T max than EPL powder. Acute oral toxicity study showed that EPL-NCs do not pose any toxicity concern to the blood and vital organs. Consequently, NCs prepared by controlled crystallization technique present a promising strategy to improve solubility profile, dissolution velocity and bioavailability of poorly water-soluble drugs.
BACKGROUND Ajuga bracteosa is a traditional herb used against various diseases. OBJECTIVE Current... more BACKGROUND Ajuga bracteosa is a traditional herb used against various diseases. OBJECTIVE Current research aimed to investigate the anti-diabetic and hepato-protective effect of green synthesized silver nanoparticles (ABAgNPs) using Ajuga bracteosa aqueous extract (ABaqu). METHODS In vitro anti-diabetic and cytotoxic effects were carried out via α- glucosidase inhibition, brine shrimp lethality, and protein kinase inhibition assays. For in vivo screening of 200 mg/kg and 400 mg/kg of both ABAgNPs and ABaqu in alloxan-induced and CCl4-induced Swiss albino mice were used. Liver and kidney functional markers, hematology, and histopathological studies were carried out after 14 days of administration. RESULTS In vivo antidiabetic and anti-cancerous effects showed valuable anti-hyperglycemic and hepato-protective potential when mice were treated with ABaqu and ABAgNPs. A significant reduction in the blood glucose level was recorded when ABaqu and ABAgNPs were administrated orally compared...
Mental retardation, also termed as learning impairment or cognitive dysfunction, is a serious man... more Mental retardation, also termed as learning impairment or cognitive dysfunction, is a serious manifestation of nervous system. The defining features of mental retardation are low or subaverage intellectual functioning (Intelligence quotient<70), impairment in at least two of the adaptive skills (e.g communication ability, self care, self guidance, reading, writing ability, etc) before 18 year of age1. Molecular cytogenetics is the study of genetic disorders using advanced technologies combined with cytogenetic and molecular methodologies2. Molecular diagnosis has equal importance as clinical diagnosis in mental retardation and day by day new advancement in these methodologies are being introduced by molecular cytogeneticists. The promising achievement of molecular cytogenetic techniques is the genetic counseling of high risk pregnancies. The current mini-survey of literature discusses an overview of these techniques employed to investigate deletion, duplication, inversion and tra...
BACKGROUND XPD Lys751Gln polymorphism may modulate inter-individual variation in repair capacity ... more BACKGROUND XPD Lys751Gln polymorphism may modulate inter-individual variation in repair capacity of DNA, which may enhance a person's susceptibility to develop colorectal cancer (CRC). The analysis of XPD Lys751Gln polymorphism may provide important information for identifying high-risk individuals and for selecting the most appropriate treatment for poor prognostic CRC patients. OBJECTIVE The overall objective was to find out the association of XPD Lys751Gln gene polymorphism with the risk of having a colorectal cancer and the ultimate clinical outcomes. In this study a total of 300 subjects (CRC and Controls), were genotyped for XPD Lys751Gln. METHODS Using PCR-RFLP methods, the association of XPD Lys751Gln gene polymorphism with the risk of having a colorectal cancer was studied. In addition to overall risk assessment, genotyping results were also investigated with respect to the lifestyle risk factors, patients treated with oxaliplatin-based chemotherapy and clinicopathological characteristics. RESULTS The overall correlation between the XPD Lys751Gln genetic variation and the CRC risk was observed to be significant with both the homozygous variant genotype Gln/Gln as well as heterozygous genotype Lys/Gln being associated with the increased risk of CRC. Additional stratified analyses revealed that XPD Lys751Gln variants remarkably increased risk of CRC in males and younger individuals (≤ 50 years), Naswar users (8.09-fold) and high intake of red meat. CONCLUSIONS Our findings suggest that the relationship between the XPD Lys751Gln variants and lifestyle factors modulates the risk for CRC in Pakistani population.
As the founding editor, it is my privilege and indeed an honour to write this inaugural editorial... more As the founding editor, it is my privilege and indeed an honour to write this inaugural editorial on the launch of the Pakistan Journal of Nuclear Medicine (PJNM), the official journal of the Pakistan Society of Nuclear Medicine and the first nuclear medicine journal being published from Pakistan. PJNM aspires to represent the professional excellence and contributions of the nuclear medicine community in Pakistan at an international level. This peer-reviewed journal aims to contribute towards research and education of physicians in the field of nuclear medicine and allied sciences. The journal shall provide a platform
Background: Multi-drug resistance in bacterial pathogens is a rising concern today. Green synthes... more Background: Multi-drug resistance in bacterial pathogens is a rising concern today. Green synthesis technology has been utilized to cure infectious diseases. Objectives: The aim of the current research was to highlight the antibacterial, antioxidant, and phytochemical screening of green synthesized silver nanoparticles using Ajuga bracteosa. Methods: Extract of A. bracteosa was prepared by maceration technique. Silver nanoparticles were synthesized using A. bracteosa extract and were confirmed by UV-vis spectrophotometer, Scanning electron microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The antibacterial, anti-biofilm, cell proliferation inhibition, TLC-Bioautography, TLC-Spot screening, antioxidant, and phytochemical screening were also investigated. Results: UV-viz spectrum and Scanning electron microscopy indicated the synthesis of green nanoparticles at 400 nm with tube like structures. FTIR spectrum showed the functional groups have a role in capping and st...
Nanocarriers endow tremendous benefits to the drug delivery systems depending upon the specific p... more Nanocarriers endow tremendous benefits to the drug delivery systems depending upon the specific properties of either component. These benefits include, increase in the drug blood retention time, reduced efflux, additional toxicity and targeted delivery. Methotrexate (MTX) is clinically used for cancer treatment. Higher dosage of MTX results in hepatic and renal toxicity. In this study methotrexate silver nanoparticles (Ag-MTX) coated with polyethylene glycol (PEG) are synthesized and characterized. Their anticancer activity and biocompatibility is also evaluated. Ag-MTX nanoparticles are synthesized by chemical reduction method. They are characterized by Ultraviolet-Visible Spectroscopy and Fourier Transform Infrared Spectroscopy. Average size of PEG coated Ag-MTX nanoparticles (PEG-Ag-MTX nanoparticles) is 12nm. These particles exhibited improved anticancer activity against MCF-7 cell line. Hemolytic activity of these particles was significantly less than MTX. PEG-Ag-MTX nanoparticles are potential nanocarrier of methotrexate which may offer MTX based cancer treatment with reduced side effects. In-vivo investigations should be carried out to explore them in detail.
Typhoid is a major health problem but conventional diagnostic methods are inadequate.OBJECTIVES: ... more Typhoid is a major health problem but conventional diagnostic methods are inadequate.OBJECTIVES: Comparison of two latest diagnostic techniques, PCR and Typhidot. SUBJECT& METHODS: Blood samples from 20 patients of suspected early ...
A simple and selective capillary electrophoretic method was established for the simultaneous dete... more A simple and selective capillary electrophoretic method was established for the simultaneous determination of methotrexate (MTX), 7-hydroxymethotrexate (7-OHMTX), 2,4-diamino-N10-methylpteroic acid (DAMPA), and polyglutamate derivatives [MTX-(Glu)n, n=2-7] in whole blood. After extraction, those analytes were separated by fused-silica capillary and a running buffer containing glycine (1.2 M, pH 9.3). The quantitative ranges were 10-50 microM for each analyte. The intra- and inter-day RSD and RE values were all less than 6 and 11%, respectively. The limits of detection (S/N= 3, injection 5 s) were found to be 1 microM for MTX, 7-OHMTX, MTX-(Glu)2, MTX-(Glu)3, and MTX-(Glu)4; 3 microM for MTX-(Glu)5 and MTX-(Glu)6; 5 microM for MTX-(Glu)7, and 8 microM for DAMPA. All recoveries were greater than 94%. This method was applied to blood MTX monitoring in a patient with acute lymphoblastic leukemia.
International Journal of Polymeric Materials and Polymeric Biomaterials
ABSTRACT Sorafenib is the only approved targeted agent against hepatocellular carcinoma (HCC). It... more ABSTRACT Sorafenib is the only approved targeted agent against hepatocellular carcinoma (HCC). It has several limitations predominantly poor aqueous solubility and hepatic first-pass effect that limits its oral delivery leading to low bioavailability, large inter-subject variability, narrow therapeutic window and side effects. Tosylate is used to improve its solubility, which is practically insoluble in water (60 µg/mL) so problems with sorafenib solubility persist. To improve the paharmacokinetic profile, minimize the side effects, and targeting drug to the tumor tissues, several polymeric nano-formulations are being evaluated. In this comprehensive review, various reported polymeric nano-delivery systems for sorafenib are comprehensively covered. GRAPHICAL ABSTRACT
Methotrexate (MTX) is a well-known chemotherapeutic agent for solid tumor. However, its clinical ... more Methotrexate (MTX) is a well-known chemotherapeutic agent for solid tumor. However, its clinical usage is limited due to low permeability, cellular drug efflux, and non-specific drug delivery. These constraints require dose dumping and result in dose-dependent toxic effects. In the current study, MTX-loaded PEGylated gold nanoparticles (PEG-MTX-AuNPs) exposed to acidic pH (tumor cell) trigger a significant drug release profile. MTX was conjugated to citrate functionalized AuNP and stabilized by thiolated methyl polyethylene glycol (mPEG-SH). PEG-MTX-AuNP was cationic with 39.5 ± 1.2 mV zeta potential and a particle size of 39 nm, as revealed by DLS and TEM. AuNP size ranging from 40 to 50 nm was favorable for maximum endosomal uptake and fast drug release. MTX-AuNP showed 39.4% (22.28 µg/ml) drug loading efficiency. Spectroscopic examinations confirmed MTX chemisorption onto AuNPs via carboxyl (–COOH) and gold dative bond. In vitro release study indicated a 6.5-fold increased MTX release in the acidic environment (pH 4.5) compared to physiological pH. The terminal mPEG provided stability in a biological medium, refrained from protein deactivation, and exhibited significant hemocompatibility (less than 5% hemolysis up to 10 μM concentration). In vitro cytotoxicity against human rhabdomyosarcoma (RD) cells indicated significant (p < 0.0001) anticancer activity of PEG-MTX-AuNPs with low median growth inhibition concentration (GI50 = 3.61 ± 0.94 μM) compared to MTX (13.12 ± 0.98 μM) and AuNPs (5.24 ± 0.98 μM) alone. In conclusion, PEG-MTX-AuNPs offer higher stability in ionic and biological media, hemocompatibility, and acidic pH-dependent MTX release, and mediate enhanced in vitro anticancer activity that makes them a potential candidate for skeletal muscle sarcomas. Methotrexate (MTX) is a weak dicarboxylic acid which become ionized at pH 7.4 (PBS) and unionized at endosomal pH 4.5. In ionized state MTX exchanges the negatively charged citrate ions and chemisorbed on AuNPs surface to stabilize and cap AuNPs. While in acidic media MTX become unionized and released in media. The enhanced intracellular release improves therapeutic outcome of MTX. The chemisorption of MTX was further confirmed with FTIR, supported by XRD and UV results.Scheme 1 Methotrexate binding mechanism to AuNP surface Methotrexate binding mechanism to AuNP surface
Current pharmaceutical biotechnology, Jan 17, 2018
Many health hazardous diseases are caused by clinical pathogens. Drug-resistant microbes are one ... more Many health hazardous diseases are caused by clinical pathogens. Drug-resistant microbes are one of the major health problems in the world. To overcome the effect of infectious diseases new antimicrobial agent from nature has been explored which is environmentally friendly, less costly and more effective for the development of next-generation drugs. Bergenia ciliata and silver nitrate both have medicinal properties. The aim of the current research was to evaluate the cytotoxic, and antibacterial effect of green synthesized nanoparticles using Bergenia ciliata rhizome against clinical bacterial pathogens. Extract of Bergenia ciliata was prepared by maceration technique. Silver nanoparticles were synthesized using Bergenia ciliata rhizome extract. Synthesized silver nanoparticles were confirmed by UV-vis spectrophotometer, Scanning electron microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The antibacterial, anti-biofilm, cell proliferation inhibition, DNA protectio...
Tailoring personalized cancer nanomedicines demands detailed understanding of the tumor microenvi... more Tailoring personalized cancer nanomedicines demands detailed understanding of the tumor microenvironment. In recent years, smart upconversion nanoparticles with the ability to exploit the unique characteristics of the tumor microenvironment for precise targeting have been designed. To activate upconversion nanoparticles, various bio-physicochemical characteristics of the tumor microenvironment, namely, acidic pH, redox reactants, and hypoxia, are exploited. Stimuli-responsive upconversion nanoparticles also utilize the excessive presence of adenosine triphosphate (ATP), riboflavin, and Zn2+ in tumors. An overview of the design of stimulus-responsive upconversion nanoparticles that precisely target and respond to tumors via targeting the tumor microenvironment and intracellular signals is provided. Detailed understanding of the tumor microenvironment and the personalized design of upconversion nanoparticles will result in more effective clinical translation.
This study was aimed to develop doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan ... more This study was aimed to develop doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan (DOX-GCPQ) nanoformulation that could enable DOX delivery and noninvasive monitoring of drug accumulation and biodistribution at tumor site utilizing selfflorescent property of doxorubicin. Materials and methods: DOX-GCPQ amphiphilic polymeric nanoformulations were prepared and optimized using artificial neural network (ANN) and characterized for surface morphology by atomic force microscopy, particle size with polydispersity index (PDI), and zeta potential by dynamic light scattering. Fourier transformed infrared (FTIR) and X-ray diffractometer studies were performed to examine drug polymer interaction. The ANN-optimized nanoformulation was investigated for in vitro release, cellular, tumor, and tissue uptake. Results: The optimized DOX-GCPQ nanoformulation was anionic spherical micelles with the hydrodynamic particle size of 97.8±1.5 nm, the PDI of ,0.3, the zeta potential of 28±2 mV, and the encapsulation efficiency of 80%±1.5%. Nanoformulation demonstrated a sustained release pattern over 48 h, assuming Weibull model. Fluorescence microscopy revealed higher uptake of DOX-GCPQ in human rhabdomyosarcoma (RD) cells as compared to free DOX. In vitro cytotoxicity assay indicated a significant cytotoxicity of DOX-GCPQ against RD cells as compared to DOX and blank GCPQ (P,0.05). DOX-GCPQ exhibited low IC 50 (1.7±0.404 µmol) when compared to that of DOX (3.0±0.968 µmol). In skin tumor xenografts, optical imaging revealed significantly lower DOX-GCPQ in heart and liver (P,0.05) and accumulated mainly in tumor (P,0.05) as compared to other tissues. Conclusion: The features of nanoformulation, ie, small particle size, sustained drug release, and enhanced cellular uptake, potential to target tumor passively coupled with the possibility of monitoring of tumor localization by optical imaging may make DOX-GCPQ an efficient nanotheranostic system.
A regulated immune system employs multiple cell types, diverse variety of cytokines and interacti... more A regulated immune system employs multiple cell types, diverse variety of cytokines and interacting signalling networks against infections. Systems biology offers a promising solution to model and simulate such large populations of interacting components of immune systems holistically. This study focuses on the distinct components of the adaptive immune system and analysis, both individually and in association with HCV infection. The effective and failed adaptive immune response models have been developed followed by interventions/perturbations of various treatment strategies to get better assessment of the treatment responses under varying stimuli. Based on the model predictions, the NK cells, T regulatory cells, IL-10, IL-21, IL-12, IL-2 entities are found to be the most critical determinants of treatment response. The proposed potential immunomodulatory therapeutic interventions include IL-21 treatment, blocking of inhibitory receptors on T-cells and exogenous anti-IL-10 antibody...
Background: Hepatitis C virus (HCV) is a major cause of chronic liver infection, which may lead t... more Background: Hepatitis C virus (HCV) is a major cause of chronic liver infection, which may lead to liver cirrhosis, fibrosis, and hepatocellular carcinoma while about one-fourth of the infected patients recover spontaneously. The host immune response remains decisive in the outcomes of antiviral treatment. Single nucleotide polymorphisms (SNPs) at the genes within the human leukocyte antigen (HLA) cluster are associated with differential immune response and treatment outcomes. Objectives: This study aimed to determine the association of SNPs in Tumor necrosis factor-alpha (TNF-α) and HLA genes (HLA-DRB1 and HLA-DQB1) with the outcomes of HCV infection and anti-HCV therapy. Methods: The study included 245 HCV-infected patients visiting a tertiary care hospital, located in Islamabad, Pakistan. Viral quantification and genotyping were performed by real-time PCR. Twenty SNPs in TNF-α, HLA-DRB1, and HLA-DQB1 were sequence-genotyped by the Sanger method in 180 patients. Multivariate logistic regression was performed to establish the association of SNPs with spontaneous clearance of the virus and response to anti-HCV therapy. Results: Five out of 20 SNPs were novel. Allelic variants at three different locations (HLA-DRB1, rs2308802; HLA-DQB1,-8447, and HLA-DQB1,-8471) showed significant associations with two groups of HCV patients receiving anti-HCV treatment (responsive and nonresponsive). Multivariate analyses disclosed that genotype A/A at HLA-DQB1 (-8471) was a significant predictor of positive response to treatment although in the presence of the variant at HLA-DRB1 (rs230880) (P = 0.004). However, no association was detected between the haplotypes constructed for the three sets of SNPs and different categories of patients. Conclusions: This study established a novel SNP HLA-DQB1(-8471) as an important predictor of an effective response to anti-HCV therapy in HCV-infected Pakistani patients. Prescreening of this variant before therapy would benefit HCV patients.
Approximately 10 million people in Pakistan are infected with the hepatitis C virus (HCV). Most p... more Approximately 10 million people in Pakistan are infected with the hepatitis C virus (HCV). Most patients develop chronic hepatitis, with rare cases of spontaneous clearance. However, little is known about multidrug resistant viral variants in Pakistan. This case study describes a 47-year-old male diagnosed with chronic HCV genotype 3a infection in 2003. After an initial diagnosis of viral infection, the patient remained treatment naïve for 5 years. He received two therapy cycles of interferon (IFN) plus ribavirin (RBV) in 2007 and 2010, however, he was non-responsive to the therapy. The patient then received an additional two treatment cycles of pegylated IFN α-2b plus RBV (in 2011 and 2013); he was still non-responsive. In 2016, the patient underwent sofosbuvir plus RBV combination therapy, however, the sustained virological response was still not achieved. The host genetic factor was found to be heterozygous guanine and thymine (GT) and cytosine and thymine (CT) genotypes of rs809...
Uploads
Papers by Abida Raza