Characterization and gastroprotective effects of Rosa brunonii Lindl. fruit on gastric mucosal injury in experimental rats - A preliminary study.

Gastric ulcer is the most prevalent disorder affecting a large population. Rosa brunonii Lindl. fruit (RBF) has traditionally been used to treat stomach pains. Therefore, the current work aimed to isolate, characterize, and investigate the gastro-protective effect of Rosa brunonii Lindl. fruit chloroform extract (RBFCE) against ethanol-induced gastric ulcers in rats. Quercetin 3-O-glucoside (QUE-G) was isolated and characterized by modern spectroscopic techniques. RBFCE was orally administered at 250 mg/kg, 500 mg/kg, and 750 mg/kg doses for ten days. Gastric ulcer was induced by a single dose of absolute ethanol (5 ml/kg) on the last day of the study. Histological changes were calculated, along with ulcer inhibition and the ulcer index (UI). Gastric juice volume, pH, acidity, mucus content, and protein content were evaluated to understand the mechanism underlying its gastroprotective effect. Omeprazole (OMP) was used as the positive control. RBFCE at a dose of 750 mg/kg significantly (p<0.01) reduced the UI (3.54) and increased the protection rate (67.63%) compared to the negative (ulcer) control group. Treatment with RBFCE in a dose-dependent manner increased the gastric pH, mucus content, and total protein while decreasing gastric juice volume and total acidity. Histopathological studies showed severe gastric mucosal injury and edema in ulcer control animals compared to extract-treated groups. This study demonstrated that oral administration of RBFCE possesses a significant gastroprotective effect due to its anti-secretory and cytoprotective mechanisms. Our findings support the traditional use of RBF to treat the gastric ulcer.

Phylogenetic diversity and mutational analysis of New Delhi Metallo-ß-lactamase (NDM) producing E. coli strains from pediatric patients in Pakistan.

The evolution of NDM genes (bla NDM) in E. coli is accounted for expansive multidrug resistance (MDR), causing severe infections and morbidities in the pediatric population. This study aimed to analyze the phylogeny and mutations in NDM variants of E. coli recovered from the pediatric population. Carbapenem-resistant clinical strains of E. coli were identified using microbiological phenotypic techniques. PCR technique used to amplify the bla NDM genes, identified on agarose gel, and analyzed by DNA sequencing. The amino acid substitutions were examined for mutations after aligning with wild types. Mutational and phylogenetic analysis was performed using Lasergene, NCBI blastn, Clustal Omega, and MEGA software, whereas PHYRE2 software was used for the protein structure predictions. PCR amplification of the bla NDM genes detected 113 clinical strains of E. coli with the contribution of bla NDM-1 (46%), bla NDM-4 (3.5%), and bla NDM-5 (50%) variants. DNA sequencing of bla NDM variants showed homology to the previously described bla NDM-1, bla NDM-4, and bla NDM-5 genes available at GenBank and NCBI database. In addition, the mutational analysis revealed in frame substitutions of Pro60Ala and Pro59Ala in bla NDM-4 and bla NDM-5, respectively. The bla NDM-1 was ortholog with related sequences of E. coli available at GenBank. The phylogenetic analysis indicated that the NDM gene variants resemble other microbes reported globally with some new mutational sites.

Chemical and pharmacological comparison of modern and traditional dosage forms of Joshanda.

Recently, a traditional remedy (Joshanda) has been replaced largely by modern ready-to-use dosage forms, which have not been compared to the original remedy. Therefore, the present study aimed to compare a number of modern dosage forms with traditional remedy. Seven brands, 3 batches each, were compared with a Lab-made formulation with reference to analytical (proximate analyses, spectroscopic and chromatographic metabolomes) and pharmacological profiles (anti-inflammatory and antibacterial activities). Chemical and pharmacological differences were found between Lab-made Joshanda and modern dosage forms. Such variations were also found within the brands and batches of modern formulations (p < 0.05). The Lab-made Joshanda showed significantly higher pharmacological activities as compared to modern brands (p ). The results of the present study indicate that modern dosage forms are unstandardised and less effective than the traditional remedy. Characteristic profiles obtained from Lab-made Joshanda may be used as reference to produce comparable dosage forms.

Advances in nano-delivery systems for doxorubicin: an updated insight.

Doxorubicin (DOX) is the most effective chemotherapeutic drug developed against broad range of cancers such as solid tumours, transplantable leukemias and lymphomas. Conventional DOX-induced cardiotoxicity has limited its use. FDA approved drugs i.e. non-pegylated liposomal (Myocet®) and pegylated liposomal (Doxil®) formulations have no doubt shown comparatively reduced cardiotoxicity, but has raised new toxicity issues. The entrapment of DOX in biocompatible, biodegradable and safe nano delivery systems can prevent its degradation in circulation minimising its toxicity with increased half-life, enhanced pharmacokinetic profile leading to improved patient compliance. In addition, nano delivery systems can actively and passively target the tumour resulting increase in therapeutic index and decreased side effects of drug. Foreseeing the need of a comprehensive review on DOX nanoformulations, in this article we for the first time have given an updated insight on DOX nano delivery systems.

Cell to rodent: toxicological profiling of folate grafted thiomer enveloped nanoliposomes.

Polymeric nanomaterials, hybridized with lipid components, e.g. phosphocholine or fatty acids, are currently being explored for efficient nano-platforms for hydrophobic drugs. However, their toxicology and toxicokinetics need to be established before enabling their clinical potential. The aim of this study was to investigate the toxicological profile of thiomer enveloped hybrid nanoliposomes (ENLs) and bare nanoliposomes (NLs), loaded with docetaxel (DTX) hydrophobic drug, biocompatible nano-carriers for therapeutic cargo. The in vitro toxicity of hybrid ENLs and NLs was evaluated towards the HCT-116 colon cancer cell line. Biocompatibility was explored against macrophages and acute oral toxicity was examined in mice for 14 days. The anticancer IC50 for ENLs was 0.148 µg ml-1 compared with 2.38 µg ml-1 for pure docetaxel (DTX). The human macrophage viability remained above 65% and demonstrated a high level of biocompatibility and safety of ENLs. In vivo acute oral toxicity showed slight changes in serum biochemistry and haematology but no significant toxicities were observed referring to the safety of DTX loaded hybrid ENLs. On histological examination, no lesions were determined on the liver, heart and kidney. These studies showed that hybrid ENLs can serve as a safe and biocompatible platform for oral delivery of hydrophobic drugs.

Is folklore use of Euphorbia helioscopia devoid of toxic effects?

OBJECTIVE: To evaluate acute toxic effects of Euphorbia helioscopia in order to assure the safety and usefulness of herbal remedy. MATERIALS AND METHODS: The Organization for Economic Cooperation and Development (OECD) for chemical testing guidelines No. 425 for acute oral toxicity testing were followed in this study. Mice were divided into three groups (n = 5). Group I served as control. Groups II and III were administered methanol extract of E. helioscopia leaves and latex orally at dose of 2000 mg/kg, respectively. Then, all the animals were observed for two weeks. Blood sampling was done by cardiac puncture after 14 days from each group for biochemical analysis. Histopathology was performed to find out any microscopic lesion in vital organs. RESULTS AND DISCUSSION: LD50 was found greater than 2000 mg/kg. There was decrease in cholesterol, triglycerides, LDL and VLDL levels of latex and leaves with methanol extract-treated animals, with respect to control indicating plant's hypolipidemic effect. On macroscopic examination, no lesions were found on vital organs, such as liver, heart and kidney; and normal architecture was observed on microscopic examination. CONCLUSION: On the basis of results, it was concluded that methanol extract of E. helioscopia leaves and latex were devoid of toxic effects in acute toxicity study.

Folate grafted thiolated chitosan enveloped nanoliposomes with enhanced oral bioavailability and anticancer activity of docetaxel.

Folate grafted and thiolated chitosan was synthesized and wrapped on the surface of mixed phosphatidylcholine based nanoliposomes (NLs) to improve the oral absorption and targeted pharmacological activity of anti-cancer drugs against breast cancer. In this study, a chitosan derived thiomer, having intrinsic properties of P-glycoprotein (P-gp) efflux pump inhibition, mucoadhesion and controlled drug release at a target site, was exploited to improve the performance of docetaxel (DTX) loaded NLs for better oral pharmacokinetics, targeted anti-cancer activity, liposomal stability and the physical characteristics of NLs. Thiomer enveloped nanoliposomes (ENLs) and bare nanoliposomes (NLs) were synthesized with the ingredient ratio pre-determined via Response Surface Methodology (RSM) plots by Design Expert® software. ENLs and NLs were thoroughly characterized for their surface chemistry, particle size, zeta potential, PDI, encapsulation efficiency, stability and release profile. ENLs were spherical in shape with a particle size of 328.5 ± 30 nm, a positive zeta potential of 18.81 ± 2.45 and a high encapsulation efficiency of 83% for DTX. Controlled release of DTX from formulations was observed for over 72 h for each formulation. The presence of thiol groups at the surface of the ENLs resulted in higher swelling and in situ gelling properties compared to the corresponding NLs. Furthermore, ENL/mucin mixtures showed a time dependent increase in viscosity for up to 12 h, leading to a 19.07-fold increased viscosity. Ex vivo permeation and P-glycoprotein inhibiting properties, studied in rat's small intestine, showed a 9.6-fold higher permeation and 13-fold enhancement of DTX in the presence of ENLs. In vitro cytotoxicity studies indicated that the ENLs can efficiently kill MD-MB-231 breast cancer cells with 200 fold lower IC50 values than DTX alone as a positive control. The pharmacokinetic study revealed that the ENLs significantly improved the oral bioavailability of DTX i.e. up to 13.6 fold as compared to an aqueous dispersion of DTX. Therefore, these enveloped hybrid nanoliposomes (ENLs) have the potential to be developed as useful nanocarriers for efficient oral delivery and breast cancer management using DTX.