Development and DoE-ANN based optimization of novel swellable matrix-diffusible doxorubicin loaded zinc oxide nanoflowers using sonochemical-precipitation method.

This research aimed to acquire doxorubicin loaded zinc oxide nanoflowers (DOX-ZnO-NFs) for intracellular drug cargo possessing a synergistic in-vitro anticancer activity with minimal toxicity. Zinc is the main inorganic metallic component of various enzyme systems and has the possibility of fabrication into the diverse nano-structural forms. An easy absorption and extensive tissue distribution of zinc have made it unique candidate for drug delivery system. Hence, the zinc oxide nanoflowers were prepared with sonochemical-precipitation. The developed system was characterized using the reported methods and was optimized employing design of experiment, coupled with artificial neural network approach. The optimized nanoflowers (DOX-ZnO-NFV) were anionic with particle size of 24 ± 0.05 nm, polydispersity index of <0.5, a zeta potential of -25.68 ± 0.16 mV, yield of 87.40% and encapsulation efficiency of 85.25%. DOX-ZNO-NFV depicted sustained DOX release, around 65.413% release in 30 h at pH 7.4 and assumed Weibull model with its derived parameters, a and b of 22.77 and 0.918, respectively. DOX-ZnO-NFV remained stable on storage for 3 months at 4° C/50% RH and 25° C/60% RH. DOX-ZnO-NFV displayed a zone of inhibition of 13.50 ± 1.25 mm and 25.50 ± 0.98 mm, respectively against gram-positive Staphylococcus aureus and gram-negative Escherichia coli strains, presenting the nanoflowers as self-preservative. DOX-ZnO-NFV exhibited higher in-vitro anticancer activity in Henrietta Lacks cell line, with least hemolysis compared to the free DOX and ZnO-NF. Thus, doxorubicin loaded zinc oxide nanoflowers envisioned to act as better chemotherapeutic cargos with the maximize anticancer activity and minimal toxicity.

Enhanced Mefenamic Acid Release from Poloxamer-Silicon Dioxide Gel Filled in Hard Gelatin Capsules - An Application of Liquid Semisolid Matrix Technology for Insoluble Drug.

INTRODUCTION: Liquid Semisolid Matrix (LSSM) technology involves the filling of drugmixed gel in hard gelatin capsules for different applications. METHODS: In continuation of our previous work on LSSM technology, 10% (w/w) of practically insoluble model drug, mefenamic acid was incorporated in gels of different poloxamers with 8% (w/w) SiO2. RESULTS: Gels exhibited plasticity or pseudoplasticity along thixotropy at 2 and 24 h enabling their easy filling into hard gelatin capsules without content seepage. Mefenamic acid gels prepared with L64 and L92 maintained their apparent viscosities for the study period of one month. Around 100% mefenamic acid was released within 90 min from L64- and in 150 min from L92-SiO2 gels, both with first-order kinetics. In 12 month long-term stability studies, only mefenamic acid-L64- SiO gel at 30°C/65% RH indicated dispersion stability with similar rheology and release pattern to that at 2, 24 and 30 days. No chemical drug-polymer interactions were found in FTIR. CONCLUSION: The release of practically insoluble mefenamic acid could be enhanced from gel formulated with L64 and SiO2.

Medicinal Plants and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Treatment of Arthritis: A Literature Review.

Context: Arthritis is an inflammatory disease of diarthrodial joints and is associated with swollen inflamed joints, disruption of joints, and loss of integrity of articular cartilage and synovial joints. Objective: The current review intended to examine the data on the epidemiology, causes, clinical diagnosis, and prevention and control of different types of arthritis and on the use of medicinal plants in gouty arthritis. Design: The research team performed a literature review, searching relevant literature databases, including bioRxiv, medRxiv, Google Scholar, Embase, PsychINFO, and PubMed. The search terms were arthritis, diarthodial joints, use of medicinal plants in gouty arthritis, and synovial joints. Setting: The study took place in the main library of the University of Sargodha in Sargodha, Pakistan. Results: The research team identified 135 studies, and eventually 92 unique academic publications were included in the analysis. Arthritis can develop and progress in any musculoskeletal joint, and most commonly occurs in knees, hips, shoulders, and hands. Major risk factors for arthritis include age, obesity, trauma, other diseases, and smoking. Arthritis is classified into various types, including rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis, septic arthritis, and psoriatic arthritis (PsA). RA and OA are the most common types worldwide. RA is an autoimmune disease in which the body's immune cells attack the joints. OA develops due to damage of cartilage, tissues, and joints due to age, obesity, or stress on joints. Gouty arthritis develops due to hyperuricemia; deposits of monosodium urate crystals can lead to gouty arthritis. Septic arthritis occurs due to a microbial infection in synovial joints because in synovial joints the basement membrane is absent. PsA develops due to the psoriasis-skin disease. Conclusions: The current review showed that different types of arthritis has different causes and pathogeneses. Pain in joints is a major and common symptom in all types of arthritis. Arthritis is managed pharmacologically and nonpharmacologically. Treatment is different for each class of arthritis according to its cause and symptoms.

The Potentially Recommended Pharmacotherapy for COVID-19.

CONTEXT: A completely unique coronavirus (2019-nCoV), formally referred to as severe acute respiratory syndrome (SARS-CoV-2), appeared in China. SARS-CoV-2 is an etiological mediator of coronavirus 2 (COVID-19), characterized by pneumonic contagion in human beings. In spite of forceful suppression, this virus has spread worldwide. No specific drugs have been approved by the FDA for treating COVID-19 patients. OBJECTIVE: The study intended to examine the data from studies on clinical management of COVID-19. DESIGN: The research team performed a literature review, searching relevant literature databases. The sources of data included bioRxiv, medRxiv, Google Scholar, Embase, PsychINFO, WanFang Data, and PubMed. The search terms were treatment of the novel coronavirus, management of nCoV-19, chloroquine, and hydroxychloroquine. SETTING: The study took place in the main library of the University of Sargodha in Sargodha, Pakistan. RESULTS: The study identified 42 unique studies that had reported and confirmed over 1500 cases of nCoV-19 by April 21, 2020. The studies found that clinical management, for patients who presented with symptoms, included supportive care and control measures that comprised mechanical ventilator support and supplementary oxygen. CONCLUSIONS: There have been intensive attempts to explore drug therapy for the prophylaxis and treatment of SARS-CoV-2 infection during this COVID-19 pandemic. Several drugs have been identified which including remdesivir, two antimalarials (chloroquine and hydroxychloroquine) and immunosuppressive agents. The effects of most drug interventions are currently highly uncertain and several drugs and vaccines are under trail for the effective treatment of COVID-19 virus, until an effective treatment will discover social distancing and physical hygiene should be practiced strictly.

Devoid Knowledge and Low Adherence Precipitate Uncontrolled Blood Pressure: A Depiction From Cross-Sectional Study.

OBJECTIVE: The present study was aimed to assess knowledge regarding disease, adherence to medication and blood pressure control among hypertensive patients. METHODS: A cross-sectional study involving 384 hypertensive patients attending a tertiary care, public sector hospital in Islamabad, Pakistan, was conducted. Data was collected by using Urdu versions of pre-validated hypertension knowledge questionnaire and Medication Adherence Scale by Morisky. Each patient's blood pressure was measured through a calibrated mercury sphygmomanometer. Data was analyzed statistically by using SPSS software version 21.0. Chi-square test was performed to determine association level among study variables. Mann-Whitney and Kruskal-Wallis tests were performed to assess for statistically significant differences of demographic variables with systolic BP and diastolic BP. Multiple regression was used to predict the impact of two or more independent variables on dependent variable. P value of <.05 was considered to be significant. RESULTS: Mean (SD) systolic and diastolic blood pressures of 384 patients were 140.39 ± 15.485 and 88.74 ± 10.683 in mmHg respectively. The mean knowledge score was (13.26 ± 5.16 out of 22) and median score was 13. 103 (26.8%) of the patients had poor knowledge, whereas, 191 (49.7%) had moderate knowledge regarding hypertension with most of them at bottom line in the scale of moderate knowledge. The mean medication adherence score was (4.66 ± 2.743 out of 8), while 204 (53.1%) were categorized as poor adherent. CONCLUSION: The current study concluded that knowledge regarding hypertension, adherence to treatment and blood pressure control among hypertensive patients was found poor.

Biochemical Dynamics and Clinical Features of Novel Corona Virus (2019-nCoV).

CONTEXT: The novel Corona Virus (nCoV-19) was initially reported in Wuhan, China during December 2019, and later people with nCoV-19 were identified in different parts of the world. Infected people had shown symptoms resembling pneumonia, but about 50% of patients were asymptomatic. OBJECTIVE: The study intended to examine the data from studies on nCoV-19. DESIGN: The research team performed a literature review, searching relevant literature databases. The sources of data included bioRxiv, medRxiv, Google Scholar, Embase, PsychINFO, WanFang Data and PubMed. The search terms were novel Corona Virus, and nCoV-19 structure. SETTING: The study took place in the main library of the University of Sargodha, Sargodha, Pakistan. RESULTS: The study identified 22 studies that had reported and confirmed over 2000 cases of nCoV-19 by January 26, 2020. The studies found that the virus was transmitted through respiratory droplets. The virus has two serotypes, OC43 and 229E. CONCLUSIONS: No specific curative therapy is available for CoVid-19. However, certain precautionary measures may potentially reduce the transmission, including washing hands, using sanitizers frequently, avoiding public gatherings, and quarantining or isolating patients. This virus has spread globally and immunocompromised individuals, and especially older individuals, are at significant risk. Community and healthcare professionals have a positive role to play in controlling the spread of the disease.

Impact of pharmacist's intervention on disease related knowledge, medication adherence, HRQoL and control of blood pressure among hypertensive patients.

The present study was aimed to evaluate the effect of educational intervention provided to the patients of hypertension through pharmacist with the goal to improve knowledge about hypertension, adherence to prescribed medicines, blood pressure control and HRQoL(Health Related Quality of Life).A total of 384 patients were assigned randomly into 2 groups including intervention and control groups each having 192 patients. Urdu versions of knowledge questionnaire regarding hypertension, medication adherence scale (MMAS-U) by Morisky and EuroQol scale (EQ-5D) were utilized. Each patient's blood pressure was measured. After educational intervention, an increase was found in mean knowledge score about hypertension (18.18 ± 4.00), adherence score (5.89 ± 1.90), HRQoL score (0.73 ± 0.12) and Visual Analogue Scale (VAS) score (69.39 ± 5.90) among the IG. The blood pressure control also improved and lower systolic (131.81 ± 10.98 mmHg) and diastolic blood pressures (83.75 ± 6.21 mmHg) were observed among the patients of IG. This study showed that educational programs are useful for patients in increasing patient's levels of knowledge about hypertension, improving adherence to prescribed medication and enhancing blood pressure control. This increase is in turn accountable to improve HRQoL.

Effect of Rheology and Poloxamers Properties on Release of Drugs from Silicon Dioxide Gel-Filled Hard Gelatin Capsules-A Further Enhancement of Viability of Liquid Semisolid Matrix Technology.

The liquid and semisolid matrix technology, filling liquids, semi-solids and gels in hard gelatin capsule are promising, thus, there is a need of enhanced research interest in the technology. Therefore, the present study was aimed to investigate isoniazid (freely soluble) and metronidazole (slightly soluble) gels filled in hard gelatin capsules for the effect of poloxamers of different viscosities on release of the drugs. Gel of each drug (10% w/w, particle size 180-250 µm), prepared by mixing poloxamer and 8% w/w hydrophilic silicon dioxide (Aerosil® A200), was assessed for rheology, dispersion stability and release profile. Both the drugs remained dispersed in majority of gels for more than 30 days, and dispersions were depended on gels' viscosity, which was further depended on viscosity of poloxamers. A small change in viscosity was noted in gels on storage. FTIR spectra indicated no interactions between components of the gels. The gels exhibited thixotropic and shear-thinning behaviour, which were suitable for filling in hard gelatin capsules without any leakage from the capsules. The release of both drugs from the phase-stable gels for 30 days followed first-order kinetics and was found to be correlated to drugs' solubility, poloxamers' viscosity, polyoxyethylene contents and proportion of block copolymer (poloxamers) in the gels. The findings of the present study indicated that release of drugs of different solubilities (isoniazid and metronidazole) might be modified from gels using different poloxamers and Aerosil® A200.

Role of Natural Radiosensitizers and Cancer Cell Radioresistance: An Update.

Cancer originates from genetic mutations accumulation. Cancer stem cells have been depicted as tumorigenic cells that can differentiate and self-renew. Cancer stem cells are thought to be resistant to conventional therapy like chemotherapy and radiation therapy. Radiation therapy and chemotherapy damage carcinomic DNA cells. Because of the ability of cancer stem cells to self-renew and reproduce malignant tumors, they are the subject of intensive research. In this review, CSCs radioresistant mechanisms which include DNA damage response and natural radiosensitizers have been summed up. Reactive oxygen species play an important role in different physiological processes. ROS scavenging is responsible for regulation of reactive oxygen species generation. A researcher has proved that microRNAs regulate tumor radiation resistance. Ionizing radiation does not kill the cancer cells; rather, IR just slows down the signs and symptoms. Ionizing radiation damages DNA directly/indirectly. IR is given mostly in combination with other chemo/radiotherapies. We briefly described here the behavior of cancer stem cells and radioresistance therapies in cancer treatment. To overcome radioresistance in treatment of cancer, strategies like fractionation modification, treatment in combination, inflammation modification, and overcoming hypoxic tumor have been practiced. Natural radiosensitizers, for example, curcumin, genistein, and quercetin, are more beneficial than synthetic compounds.

Hypoglycemic activity of Ficus racemosa bark in combination with oral hypoglycemic drug in diabetic human.

Medicinal herbs, used in indigenous medicines in crude forms for the management of diabetes mellitus, contain both the organic and inorganic constituents. The aim of the study was to find out the hypoglycemic effect of Ficus racemosa in a group of diabetic subjects taking oral hypoglycemic drug. Twenty five of each, male and female, diabetic patients, selected from Fatima Jinnah Medical College, Lahore, Pakistan, taking oral hypoglycemic drug were included in this study and were given orally the extract (5 mL) of bark of Ficus racemosa (about 100 mg) two times for 15 days. Blood samples for estimation of blood glucose and parameters of liver and renal functions were estimated. It was observed that after taking the herb in combination with drug, blood glucose level (fasting and after breakfast) was markedly decreased in both male and female but significant difference was only observed in sugar level of males after 1.5 h after breakfast. To rule out herb toxicity, liver and renal functions tests of patients was also performed which were observed to be in normal range. Present investigation established a pharmacological evidence to support the folklore claim that Ficus racemosa is good anti-diabetic agent.