The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors / 药物分析学报

DNA-nanotechnology-based nano-architecture scaffolds based on circular strands were designed in the form of DNA-nanowires(DNA-NWs)as a polymer of DNA-triangles.Circularizing a scaffold strand(84-NT)was the critical step followed by annealing with various staple strands to make stiff DNA-triangles.Atomic force microcopy(AFM),native polyacrylamide gel electrophoresis(PAGE),UV-analysis,MTT-assay,flow cytometry,and confocal imaging were performed to assess the formulated DNA-NWs and cisplatin(CPT)loading.The AFM and confocal microscopy images revealed a uniform shape and size distribution of the DNA-NWs,with lengths ranging from 2 to 4 μm and diameters ranging from 150 to 300 nm.One sharp band at the top of the lane(500 bp level)with the loss of electrophoretic mobility during the PAGE(native)gel analysis revealed the successful fabrication of DNA-NWs.The loading efficiency of CPT ranged from 66.85％to 97.35％.MTT and flow cytometry results showed biocompatibility of the blank DNA-NWs even at 95％concentration compared with the CPT-loaded DNA-NWs.The CPT-loaded DNA-NWs exhibited enhanced apoptosis(22％)compared to the apoptosis(7％)induced by the blank DNA-NWs.The release of CPT from the DNA-NWs was sustained at＜75％for 6 h in the presence of serum,demonstrating suitability for systemic applications.The IC50 of CPT@DNA-NWs was reduced to 12.8 nM CPT,as compared with the free CPT solution exhibiting an IC50 of 51.2 nM.Confocal imaging revealed the targetability,surface binding,and slow internalization of the DNA-NWs in the scavenger-receptor-rich cancer cell line(HepG2)compared with the control cell line.

Argemone mexicana extract alleviates gastrointestinal disorders by stimulating muscarinic receptors and blocking voltage-gated L-type calcium channels

Objective: To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods: The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath. The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System. The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis, respectively. Results: The total phenolic and total flavonoids contents of the extract were (267.75 ± 5.77) mg GAE/g and (73.86 ± 6.01) mg QE/g, respectively. Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC50 value of 0.016 mg/mL, which was blocked by atropine (0.3 μM). Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC50 value of 2.185 mg/mL. Furthermore, Argemone mexicana extract relaxed potassium (80 mM)-induced contractions (EC50: 9.07 mg/mL), similar to a standard drug verapamil. The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract (1-5 mg/mL) and verapamil (0.1-1 μM). In addition, the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks. Conclusions: Argemone mexicana shows cholinergic agonist and calcium channel blocker activities, as well as antiemetic effect. It may be used as a potential agent for treating gastrointestinal disorders.

Chemical characterization, docking studies, anti-arthritic activity and acute oral toxicity of Convolvulus arvensis L. leaves

Objective: To evaluate acute oral toxicity and anti-arthritic activity of the methanolic extract of Convolvulus arvensis L. leaves. Methods: Safety was assessed by acute oral toxicity (OECD 425) study. Anti-arthritic activity was explored by in vitro (inhibition of protein denaturation) and in vivo (Complete Freund's adjuvant-induced arthritis and carrageenan-induced inflammation) methods. Antioxidant potential was determined by assessing ferric reducing power, DPPH inhibition, and H2O2 scavenging assays. Furthermore, molecular docking was done to check interactions between the plant constituents and cyclooxygenases (COX-1 and COX-2). Quercetin, gallic acid, caffeic acid, syringic acid, sinapic acid, and vanillic acid were quantified by HPLC and eight compounds were identified by GC-MS analysis. Results: No mortality and abnormality in biochemical parameters were observed in the toxicity study. Histological analysis of vital organs also supported these biochemical results. The in vitro and in vivo studies showed that the methanolic extract of leaves of Convolvulus arvensis exhibited dose-dependent anti-arthritic and anti-oxidant potential. Molecular docking showed better interactions of plant compounds with cyclooxygenases as compared to standard ibuprofen. Conclusions: Convolvulus arvensis exhibits strong anti-arthritic activity, justifying the traditional use of the herbal drug.

Polymer blend: a new approach for eliminating curing effect of aqueous dispersion coatings

The aim of present work was to investigate blends of Eudragit® NE 30D with Aquacoat® ECD using different ratios to eliminate curing effect associated with individual polymers. Propranolol HCl 10% w/w was layered onto sugar cores using 5% w/w HPMC as a binder. Drug-layered-cores were coated either with pure or blends of Aquacoat® ECD: Eudragit® NE 30D in a fluidized bed coater to obtain 20% w/w coating level. Talc 35% w/w was used as anti-tacking agent. The pellets were characterized for in vitro dissolution studies, morphology, water uptake-weight loss, osmolality and adhesion of coating after curing at 60 °C or 60 °C/75% RH for 24 h. The findings revealed that Aquacoat® ECD coated pellets showed curing effect due to further gradual coalescence of polymeric particles which resulted into better film formation upon curing. In contrast, the curing effect of Eudragit® NE 30D coated pellets was caused by decrease in adhesion of coatings after curing which provided entirely different swelling behavior of uncured (localized swelling) and cured (uniform swelling) pellets. The undesired curing effect of individual polymers was eliminated by using their blends in appropriate ratio.

Formulation, evaluation and release rate characteristics of medicated jelly of vitamin C

Medicated jelly formulations are patient friendly dosage form for pediatric, geriatric and dysphagic patients. These formulations offer rapid dissolution and absorption of drugs through oral mucosa therefore show the early onset of action. The objective of the study was to develop and evaluate oral jelly formulations of vitamin C. Slurry method was adopted using glucose 103gm, sugar 67gm, gelatin 10gm and sorbitol 6.56gm. Preformulation studies were performed including the organoleptic profile, pH, and solubility of both drugs. The medicated jelly of Vitamin C was prepared and evaluated for physical characteristics, weight variation, syneresis, pH, taste and palatability, drug content, release rate characteristics and stability studies. All the jellies were found to have patient welcoming taste and were palatable. All formulations showed more than 50% drug release within 15 minutes, while 93% drug was released in 30 minutes. The results of release kinetics showed that the formulation followed the zero order release kinetics. Thus the drug was released at constant rate independent of the drug concentration involved in the process. All the medicated jellies were found to remain stable stored for 60 days at different temperatures. The present study revealed that medicated jellies of vitamin C could be employed orally in an effective form as an alternative solid oral dosage form for special population such as pediatrics, geriatrics and patients with dysphagia

Surface Area In Children: A Simple Formula.

We retrospectively compared body surface area (BSA) using the Mosteller formula √ W H ×––––– and a simple weight-based BSA formula ([4Wkg+7]/ [90+Wkg]). 3600 The participants were 363 children who underwent cardiac surgery from 1991 to 2000. Their age ranged from 5 days to 18 years, weight ranged from 1.2 kg to 98 kg and height ranged from 38 cm to 178 cm. There was excellent correlation (r2=0.991) between Mosteller formula and the new formula (P <0.001). We propose that the weight-based formula is easy to use and accurate. It can safely replace Mosteller formula and dispense the need for time-consuming calculations.