Conveyance of sofosbuvir through vesicular lipid nanocarriers as an effective strategy for management of viral meningitis.

This study aimed to deliver a potential water-soluble antiviral drug (sofosbuvir) through optimized vesicular lipid nanocarriers (LNs) to the rat brain as a novel strategy against viral meningitis. A 23 factorial design approach was established to assess the effect of formulation composition and process variables on the physicochemical properties of the LNs. Sofosbuvir-loaded LNs (SLNs) were developed by lipid layer hydration method utilizing optimized parameters and evaluated for various in vitro characterizations like FTIR, DSC, XRD, FESEM, vesicle size, zeta potential, drug carrying capacity and drug release. Plasma and brain pharmacokinetic (PK) studies were conducted in Sprague-Dawley rats. FTIR data depicted the absence of any major interaction between the drug and the excipients. DSC revealed a sharp endothermic peak for the drug. XRD showed the amorphic nature of the SLNs. Optimized SLNs were spherical as depicted from FESEM with 42.43 nm size, -49.21 mV zeta potential, 8.31% drug loading and sustained drug release in vitro. Plasma/brain PK studies depicted significant improvement in key PK parameters, viz. AUC, AUMC, MRT, and Vd, compared to those for the free drug. A more than 3.5-fold increase in MRT was observed for optimized SLNs (11.2 h) in brain tissue compared to the free drug (3.7 h). Ex vivo hemolysis data confirmed the non-toxic nature of the SLNs to human red blood cells. In silico docking study further confirmed strong interaction between the drug and selected protein 4YXP (herpes simplex) with docking score of -7.5 and 7EWQ protein (mumps virus) with docking score of -7.3. The optimized SLNs may be taken for further in vivo studies to pave the way towards clinical translation.

Temperature-dependent mucosal permeation kinetics of stigmasterol microspheres: In vivo mice model antioral candidiasis study.

Evaluation of mucosal permeation of stigmasterol from the glutaraldehyde cross linked chitosan microspheres at increasing experimental temperatures was performed. The activation energy of permeation, partition, and diffusion were estimated to understand the permeation kinetic with respect to the temperature. The formulation depicting least activation energy possessed the increased permeation thresholds of drug at the site of application. The encapsulation efficacy and mucoadhesive strength were found to be directly proportional to the polymer-emulsifier ratio. Decreased intensity in crystallography directed the molecular dispersion of microencapsulated drug. The depleted enthalpic phase transition in thermogram affirmed the stigmasterol encapsulation. The sphericity and the size of microspheres were determined by scanning electron photo micrograph. The in vivo quantification of oral Candida infection with different statistical approach and histopathological observation of infected tongue of mice on treatment with the stigmasterol encapsulated microspheres showed significant anti oral candidiasis activity by reduction of fungal colony count and recovery of papillae, reorganization of basal cell layer and newly formed papillae during 21-28 days of treatment.

Identification of bioactive constituents from different fractions of stems of Cuscuta reflexa Roxb. using GC-MS.

The GC-MS analysis of fractions of methanol extract of stem of Cuscuta reflexa (Family Convolvulaceae) was carried out using a THERMO TRACE 1300 Gas Chromatograph equipped and coupled to a mass detector THERMO TSQ 8000 spectrometer with an TG 5MS (30 m × 0.25 mm, 0.25 µm) of capillary column. Database of National Institute of Standards and Technology (NIST) library was used to identify the components. GC-MS revealed two known compounds i.e. 2-Methoxy-4-vinyl phenol (6.80%) and Benzofuran-2,3-dihydro (20.89%) and other 12 unknown compounds such as 3,5-di-tert-Butyl-4-hydroxyanisole (35.50%); Hexatriacontane (12.02%); n-Hexadecanoic acid (10.12%); Scoparone (7.97%); Hexadecanoic acid methyl ester (5.22%); 1,3-Benzenediamine, N, N, N', N' tetramethyl- (15.43%); Phenol, 4(3-hydroxy1propenyl), 2-methoxy (9.31%); Phenol, 2,4 bis (1,1dimethylethyl); 2,3,5,6-Tetramethyl para phenylene diamine (14.18%); Retinoic acid-5,6-epoxy-5,6-dihydro (20.46%); 2,4-Dihydroxy-2,5-dimethyl-3(2H)furan-3-one (10.13%); 2,3-dihydro-3,5-dihydroxy-6-methyl-2-Propyl-tetrahydro-pyran-3-ol (10.13%); Pregn-4-ene-18-oic acid (5.75%) as some of the major compounds in its different fractions. Retinoic acid-5,6-epoxy-5,6-dihydro found as major compound may be responsible for blood glucose lowering potency.

Antidiabetic effects of Cuscuta reflexa Roxb. in streptozotocin induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cuscuta reflexa Roxb. (Convolvulaceae) is traditionally used to treat diabetes mellitus by tribal people of north-east India and Bangladesh. OBJECTIVES: To evaluate the anti-diabetic effects of methanol and aqueous extracts of the aerial parts of Cuscuta reflexa Roxb. in normal, glucose loaded and Streptozotocin (STZ) induced diabetic rats. MATERIALS AND METHODS: The methanol (MECR) and aqueous (AECR) extracts (200 and 400mg/kg body weight) were administered orally to normal and diabetic rats with Metformin and solvent control as comparison groups. Long term effects like FBG, OGTT, lipid profile, HbA1c, body weight, histopathology of major organs, etc. were investigated. RESULTS: MECR and AECR did not have hypoglycemic effects in normal rats. Both AECR and MECR (400mg/kg) treatments showed significant reduction in blood glucose during OGTT in diabetic rats at 3h. Single oral administration of methanol and aqueous extracts (400mg/kg) to diabetic rats significantly reduced (p<0.05) blood glucose level to 61.90% and 55.39% respectively as compared to the Metformin group i.e. 68.32% at the end of 8h. MECR (400mg/kg body weight for 30 days to diabetic rats) showed a significant decrease (p<0.01) of blood glucose level to 60.00% as compared to other groups. The treatment also resulted an improvement in body weights, decreased HbA1c and restored lipid profile. Histopathological injury was not observed, rather repair of beta cells was seen in extract treated diabetic rats. CONCLUSION: Methanolic extract of C. reflexa has significant antidiabetic effects and improves metabolic alterations thereby justifying its traditional folkloric claims.