Methotrexate on its oral and intravenous administration results in unwanted adverse effects. This drawback can be overcome by transdermal delivery because of its painless objective for systemic drug ...administration. Transfersomes are ultra-deformable vesicles with the flexibility to reach deeper tissues of the skin. The objective of this research work was to develop methotrexate transfersomal gel by thin film hydration technique, evaluated for entrapment efficiency, deformability, mean vesicle size, and stability, and incorporated into carbopol gel for ease of handling and skin applicability for a longer period of retention on skin. MTX-TFS gel & conventional gel were characterized for consistency, transparency, viscosity, and pH. Ex-vivo skin permeation studies were performed using abdominal goat skin and drug release kinetic parameters and transdermal flux were calculated using mathematical models. The results indicate that MTX was successfully entrapped (84.77 ± 2.35 %w/w) in transfersomes having 240±1.6 nm vesicle sizes and 27.13±0.7 deformability index. The gel was permeated through the skin at a rate of 28.12±2.58 µg/cm2/hr as compared to the conventional gel (10.35±2.14 µg/cm2/ hr). From the study, it was concluded that the MTX-TFS gel can be used as a possible substitute for the conventional formulation for transdermal drug delivery due to 3 times improvement in transdermal flux.
Transdermal drug delivery influence consumer acceptance and marked increase in bioavailability of some drugs which undergoes hepatic first-pass metabolism. Fabrication of transdermal patch requires ...lots of attention regarding the amount of components used for it. Because of varied nature of polymer and plasticizer, transdermal patches have different properties and different drug release. This study is on the basis to evaluate the amount to be needed for fabrication of diclofenac transdermal patch. Study shows that Hydroxy Propyl Methyl Cellulose has great influence on transdermal patch, if it is used alone in combination with glycerin or PEG-4000 plasticizer.
Hueter-Volkmann's law regarding growth modulation suggests that increased pressure on the end plate of bone retards the growth (Hueter) and conversely, reduced pressure accelerates the growth ...(Volkmann). Literature described the same principle in Rat-tail model. Human spine and its deformity i.e. scoliosis has also same kind of pattern during the growth period which causes wedging in disc or vertebral body.
This cross sectional study in 150 patients of adolescent idiopathic scoliosis was done to evaluate vertebral body and disc wedging in scoliosis and to compare the extent of differential wedging of body and disc, in thoracic and lumbar area. We measured wedging of vertebral bodies and discs, along with two adjacent vertebrae and disc, above and below the apex and evaluated them according to severity of curve (curve < 30 degrees and curve > 30 degrees ) to find the relationship of vertebral body or disc wedging with scoliosis in thoracic and lumbar spine. We also compared the wedging and rotations of vertebrae.
In both thoracic and lumbar curves, we found that greater the degree of scoliosis, greater the wedging in both disc and body and the degree of wedging was more at apex supporting the theory of growth retardation in stress concentration area. However, the degree of wedging in vertebral body is more than the disc in thoracic spine while the wedging was more in disc than body in lumbar spine. On comparing the wedging with the rotation, we did not find any significant relationship suggesting that it has no relation with rotation.
From our study, we can conclude that wedging in disc and body are increasing with progression on scoliosis and maximum at apex; however there is differential wedging of body and disc, in thoracic and lumbar area, that is vertebral body wedging is more profound in thoracic area while disc wedging is more profound in lumbar area which possibly form 'vicious cycle' by asymmetric loading to spine for the progression of curve.
Bosentan is choice of drug for pulmonary arterial hypertension. It belongs to BCS class-II category. Due to poor solubility in aqueous media, treatment leads to frequent dosing & increasing cost of ...therapy subsequently. One cannot unseen the shortcomings of commonly existing solubility enhancement techniques such as physical and chemical modifications of the drug, salt formation, solid dispersion, complexation because of the need for sophisticated equipment, decreased yield, incomplete removal of organic solvents, etc. The novel hybridization technique is a fusion of complexation and liquisolid technique. In this research work, Bosentan was complexed with captisol in the first step. In the second step, the complex was dispersed in non-volatile solvent & mixed with the carrier using mortar-pestle followed by the addition of coating material to form a free-flowing powder. It was then compressed into tablets by mixing with other excipients. The formulation was characterized by phase solubility study, DSC, FTIR, and XRD to confirm drug-excipients compatibility, crystallinity etc. The phase solubility study showed ∼28.85 fold increase in solubility. From screening, Avicel PH101 & Parteck SLC 500 as carrier and coating material respectively & PEG-600 as non-volatile solvent were selected. Explotab as super-disintegrant and Pearlitol 100SD as direct compressible excipient were used. Optimization by 32 factorial design gave Bosentan tablet with disintegrate in time of 7–8 min and showed 87.264±0.823% drug release in 30 min higher than marketed tablet i.e. 61.750±1.226%. From the stability study, the Novel hybridization technique was proved as a choice for solubility enhancement.
The growth-inhibitory activities of an extensive series of quaternized quino4,3,2-klacridinium salts against tumor cell lines in vitro have been measured and their biological properties interpreted ...in the light of differential binding to different DNA isoforms. Selectivity for quadruplex DNA binding and stabilization by compounds were explored through an array of methods: UV absorption and fluorescence emission spectroscopy, surface plasmon resonance, and competition dialysis. Quadruplex DNA interaction was further characterized through FRET and DNA polymerase arrest assays. Telomerase inhibition, inferred from the TRAP assay, is attributed to quadruplex stabilization, supported by the strong correlation (R 2 = 0.81) across the series between quadruplex DNA binding affinity and TRAP inhibition potency. Growth inhibition potency in the NCI60 human tumor cell line panel is more marked in compounds with greater DNA duplex binding affinity (R 2 = 0.82). Quantification of relative quadruplex and duplex binding affinity constants puts some of these ligands among the most selective quadruplex DNA interactive agents reported to date.
Methotrexate is the treatment of choice for rheumatoid arthritis, having significant side effects on oral administration, prompting researchers to consider transdermal administration. Transfersomes ...can overcome the challenges of transdermal administration of drugs because of their deformable nature, allowing for greater skin penetration than other formulations. However, due to an enormous number of product and process variables, the manufacturing of transfersomes proved a pain. The goal of the research study was to use a Plackett‐Burman design to evaluate an important product and process variables connected with the preparation of methotrexate transfersomes. The influence of six product and process variables on %entrapment efficiency and vesicle deformability was investigated and according to p‐values, and the Pareto chart, the concentration of lipid, edge activator, and methotrexate were found critical variables influencing vesicle features having positive and negative effects on variables. In the future, experimental design may be used to optimize these critical parameters for further exploration in the development of methotrexate transfersomes.
Most studies comparing the Risser staging for skeletal maturity are representing the American or European standards which are not always applicable to Asian population who have relatively less height ...and body mass. There is no article available that compares the Risser sign and bone age correlation between patients with idiopathic scoliosis and patients without scoliosis.
To analyze and compare the skeletal age with the Risser sign between scoliosis and non-scoliosis group, a cross-sectional study was done in 418 scoliosis (untreated, bracing or surgically) and 256 non-scoliosis children of Korean origin. Relationship was found in both groups using Pearson correlation test.
In scoliosis group, Pearson correlation exhibited significant correlation (p < 0.01) between Risser sign and chronological age (r2 = 0.791 for girls, 0.787 for boys) and Risser sign and TW3 age (r2 = 0.718 for girls, 0.785 for boys). Non-scoliosis group also showed significant relationship (p < 0.01) between Risser sign and chronological age (r2 = 0.893 for girls, 0.879 for boys) and Risser sign and TW3 age (r2 = 0.913 for girls, 0.895 for boys). Similarly, comparing Cobb angles of each patient according to their Risser staging, exhibited that if scoliosis remains untreated Cobb angle will increase with the increase in their Risser staging (r2 = 0.363 for girls, 0.443 for boys; p < 0.01).
Our results showed that chronological age is equally as reliable as skeletal age method to compare with Risser sign, and therefore, we do not mean to imply that only the Risser sign compared with skeletal age should be considered in the decision making in idiopathic as well as non-scoliosis patients of Korean ethnicity. Concomitant indicators such as menarchal period, secondary sex characteristics, and recent growth pattern will likely reinforce our data comparing Risser sign with skeletal age in decision making.
Two short routes to novel methylated pentacyclic quinoacridinium salts have been devised. New compounds display telomerase-inhibitory potency (<1 μM) in the TRAP assay. ...3,11-Difluoro-6,8,13-trimethyl-8H-quino4,3,2-klacridinium methosulfate (12d, RHPS4, NSC 714187) has a higher selectivity for triplex and quadruplex DNA structures than the 3,6,8,11,13-pentamethyl analogue (12c, RHPS3, NSC 714186) and a low overall growth-inhibitory activity in the NCI 60 cell panel (mean GI50 13.18 μM); in addition, the activity profile of 12d does not COMPARE with agents of the topoisomerase II class. Compound 12d is soluble in water, stable in the pH range of 5−9, efficiently transported into tumor cells, and is currently the lead structure for further elaboration in this new class of telomerase inhibitor.
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