FORMULATION AND CHARACTERIZATION OF ROPINIROLE HYDROCHLORIDE LOADED SOLID LIPID NANOPARTICLES

Objective: The aim of the present study was to formulate and evaluate the Solid Lipid Nanoparticles (SLNs) of Ropinirole Hydrochloride (ROP).Methods: ROP-loaded SLNs were prepared by a double emulsion method using glyceryl monostearate (GMS) as lipid and soya lecithin as a stabilizer. All formulated ROP-loaded SLNs were characterized for its particle size and size distribution, zeta potential, % Entrapment Efficiency (EE) and drug loading. The formulations were optimized in terms of GMS to soya lecithin ratio and sonication time of primary emulsion. Shape and surface morphology of the optimized formulation was studied using optical microscopy and scanning electron microscopy. In vitro and ex vivo Study of optimized formulation was also performed and compared with a pure drug solution.Results: The particle size and polydispersity index (PDI), zeta potential and EE of optimized formulation were found to be 320±5.15 nm, 0.260±0.012,-37.9±1.43, 56.13±2.33% respectively. In vitro and ex vivo permeation study revealed that percentage cumulative drug release of optimized formulation was found to be 58.45±1.75% and 53.75±1.34 % respectively in 24 h and more than 90% drug release from pure drug solution was found to be within 6 h. Drug release from the formulation is sustained as compared to the plain drug solution which release 97.74 % (in vitro) and 88.15 % (ex vivo) of the drug within 6 h.Conclusion: From the results, it concludes that drug released from SLNs follows sustained release pattern and it will enhance the overall activity of the drug.Â

NANOEMULSION COMPONENTS SCREENING OF QUETIAPINE FUMARATE: EFFECT OF SURFACTANT AND CO SURFACTANT

Objective: Correct selection of oils, surfactants, and co surfactants along with their optimum concentration is essential to get stable and clinicallyacceptable nanoemulsions. The aim of the present study was, to provide an efficient screening approach for the excipients selection for the optimumnanoemulsion formulation development.Methods and Results: The solubility of quetiapine (QTP) fumarate in the oils (Capryol 90, isopropyl myristate, castor oil, and olive oil), surfactants(labrasol, cremophor EL, Brij L23, Tween 20, and Tween 80), and co surfactants (ethanol, isopropyl alcohol, and propylene glycol) was taken as thecriterion for selection. The maximum solubility of QTP was found to 35.54±0.91, 40.4±0.83, and 32.07±0.92 in Isopropyl myristate, Tween 20, andpropylene glycol, respectively. The effect of Tween 20/propylene glycol mass ratio on the nanoemulsion formation was also studied by varying theratio from 3:1 to 1:0 for the further optimization of the system. The highest nanoemulsion region was obtained at Tween 20/propylene glycol inthe mass ratio of 3:1. Formulations were selected from the phase diagram at which concentration of oil was constant with increasing (30, 35, 40,45% wt/wt) concentration of surfactant/co surfactant mass ratio (Smix) and subjected to thermodynamic stability tests. The optimized formulationswere characterized for particle size, viscosity, pH and refractive index measurements. All the selected formulations were found to be stable, and thedroplet size was found to be <100 nm.Conclusion: The formulations were thermodynamically stable and can be effectively used for the drug delivery applications

A comparative study on the lipid peroxidation and total antioxidant status in patients with and without varicose veins

Background: The prevalence of varicose veins was increasing with increasing age but a deviance from the normal prevalence of the female patients. The patho- physiology has yet not been clearly delineated but the role of certain enzymes leading to oxidative stress has been implicated in the causation of this disease. Therefore, the present study was conducted to compare the lipid peroxidation and total antioxidant status in the patients with and without varicose veins.Methods: This study was performed after the institutional ethical clearance and informed consent from all the participants. Patients who were admitted for the surgery of inguinal Hernia were taken as controls. The blood was obtained and its serum was used for the estimation of MDA, GPx, and total antioxidant status using commercially available kit, according to the manufacturer’s guidelines in the central research laboratory of the institute. The data was represented as Mean±S.D. and compared using students‘t’ test and a p value of <0.05 was considered the level of significance.Results: The Serum estimations of MDA, GPX and TAC on comparison to Normal Individuals did not show any statistical significance (p>0.05).Conclusions: The levels of MDA, GPX and TAC were at the upper limit of the normal ranges in patients of Varicose veins indicating that more on antioxidants as a measure of global stress index in varicose veins are needed to be performed in the future with different Antioxidants and Advent of investigative modalities for the same.

RADIOPROTECTIVE ACTIVITY OF FICUS RACEMOSA ETHANOL EXTRACT AGAINST ELECTRON BEAM INDUCED DNA DAMAGE IN VITRO, IN VIVO AND IN SILICO

Objective: To investigate the radioprotective effect of Ficus racemosa (Fr) ethanol stem bark extract against electron beam radiation (EBR) induced DNA damage using in vitro, in vivo and in silico models.Methods: The extract of Fr was tested against radiation induced DNA damage by exposing pBR322 plasmid to different EBR dose rates. Comet assay was conducted using mice which were exposed at 6Gy EBR. In silico study was performed by inhibiting p53 protein C-chain (1TUP C) using phyto chemicals of Fr.Results: The in vitro results revealed that, Fr at lower concentration (50µg) showed inhibitory effect on radiation induced DNA damage compared with control. Exposure of mice to 6Gy EBR increased comet parameters like TL (Tail length), OTM (Olive tail moment) and %T (percentage of DNA in the tail) of blood lymphocytes. Fr ethanol extract given orally prior to irradiation at a dose of 400 mg/kg body weight protected the DNA from the radiation damage. The phytochemicals of Fr showed clear interaction with p53 protein chain C, specifically binding to Arginine 248 (ARG248) and Arginine 273 (ARG273) amino acid residues thereby inhibiting the p53 protein-DNA interaction upon radiation.Conclusion: The present study indicates that Fr ethanol extract significantly reduced radiation induced DNA damage in vivo and in vitro. It also showed that the biologically active compounds of Fr have ability to inhibit wild p53 protein which is responsible for apoptosis; these compounds can be used as radioprotectors during chemotherapy to protect normal tissues surrounding cancerous tissue.Â

Association of FADS2 rs174575 gene polymorphism and insulin resistance in type 2 diabetes mellitus

Background: Many risk factors contribute to the pathogenesis of diabetes. Gene and lifestyle factors are considered to be the major contributors. A dietary pattern is attributed to be one of the lifestyle risk factors favoring diabetes. The present study aims to find an association between fatty acid desaturase (FADS) gene polymorphism and glycemic profile in type 2 diabetes mellitus (T2DM). Methodology: A total of 429 subjects were included in the study on the basis of inclusion and exclusion criteria, of which 213 and 216 subjects were diabetic and control, respectively. Body mass index was calculated. Fasting plasma glucose, glycated hemoglobin (HbA1c) and insulin were measured using commercially available kits. rs174575 of FADS2 was selected based on previous publications and identified using the dbSNP database. To compare the biochemical parameters with the genotype, the following three models were used: additive model (CC vs CG vs GG), dominant model (CC + CG vs GG), and recessive model (CC vs CG + GG). Results and Discussion: FBS, HbA1c, insulin, HOMA-IR, and HOMA-B exhibited a high and statistically significant difference between subjects and controls. The three models exhibited a statistically significant difference between FBS, HOMA-IR, and HOMA- B (p<0.05). Conclusion: The distribution of rs174575 genotype differed significantly between the subjects and controls in the present study. The study revealed that genetic variation in FADS2 is an additional facet to consider while studying the risk factors of T2DM

EFFECT OF FATTY ACID BASED FUNCTIONAL LIPIDOMICS IN WOMEN WITH BREAST CANCER

Objective: Lipid metabolism alteration is a prominent feature during malignant transformation. We investigated the difference in plasma fatty acids (FAs) and molecular biomarkers in breast cancer women and controls. Methods: This comparative study was carried out on eighty breast cancer women and forty control women. FAs were analyzed in gas chromatography and calculated as a percentage of total FAs. FA molecular markers were estimated by the FA data. Non-parametric statistical tests were used. Results: Saturated FAs were higher in the case group. Control group had higher linoleic acid (p=0.04), suggesting decreased desaturase activity. N-6 FAs were higher and n-3 FAs were lower in breast cancer cases. The n6/n3 ratio, cardiovascular risk ratio (p<0.001), and inflammatory risk ratio were high, whereas saturation index and unsaturation index (p=0.05) were lower in breast cancer cases. Conclusion: Lipidomics of the cell membrane is significantly influenced by FAs, and the dietary FAs regulate the enzymatic activities in the FA metabolism pathway

CORRELATION BETWEEN APOB100/APOA1 RATIO AND INSULIN RESISTANCE IN TYPE 2 DIABETES MELLITUS: Apolipoproteins and Type 2 diabetes mellitus

Objective: Various lipid abnormalities are associated with Type 2 diabetes, thereby increasing the risk of cardiovascular disease and metabolic syndrome. The objective of the study is to correlate apolipoprotein ratio with insulin resistance (IR) to understand its role in Type 2 diabetes mellitus. Methods: The study population included 416 subjects of which 197 were non-diabetic and remaining 219 were non-diabetic and served as control subjects. Body mass index was calculated. Fasting plasma glucose, insulin, glycated hemoglobin levels, total cholesterol, triglyceride and high-density lipoprotein, ApoA-1, and ApoB-100 were measured using commercially available kits. Statistical analysis was performed with SPSS for Windows 16.0. Significance was defined as p<0.05. Results: Apolipoprotein A-1 levels were lower in the diabetic group whereas apolipoprotein B-100 levels, apolipoprotein ratios were higher in the diabetic group. ApoB100 and apolipoportein ratio showed a positive correlation with IR. Conclusions: The study results indicate that apolipoprotein B100/ApoA-1 ratio can act as a strong biomarker for IR

A Comparative Analytical Study of Krishna Musali Choorna and Krishna Musali Kshara

Krishna Musali (Curculigo orchioides) is among the Dashapushpa, a group of ten herbs which is culturally and medically important to the people of Southern India, especially in Kerala. Krishna Musali is mentioned in various context in the names of Krishna Musali, Talapatri, Talamooli etc. and it is having Madhuratikta rasa, Ushna virya and it is Vatapittahara and Rasayana properties. In classics references about this drug can be seen in the context of Dhoomapana yoga, Kshara vidhi, Ekangasopha chikitisa etc and the Acharyas were categorized in to specific Gana or Varga based on its mode of action.  Krishna Musali Choorna and Kshara prepared based on the method of preparation mentioned in Sharangadhara Samhita. Analytical study was carried out for the purpose of standardization. For the qualitative assurance of the raw material analytical study provides the objective parameters for the standardization leading to a reproducible quality. These tests were done for evaluating the anticancer activity of Krishna Musali Choorna and Kshara in cervical cancer cell lines. The preliminary phytochemical study shows high alkalinity of Krishna Musali Kshara compared to Choorna, it supports the definition of alkali of being caustic and corrosive in nature. So, it will be helpful in the treatment of early stages of Cervical carcinoma

Oxidative Stress, Antioxidant Status and DNA Damage in Type 2 Diabetes Mellitus

ABSTRACT Diabetes mellitus is known to be associated with increased oxidative stress. Oxygen free radicals are implicated in pancreatic beta cell damage and genesis of diabetes as well as in the pathogenesis of diabetic complications like cardiovascular disease, neuropathy, retinopathy and nephropathy. The present study is to evaluate lipid peroxidation, Myeloperoxidase level, antioxidant status and DNA damage in type 2 diabetic persons and to compare the results with non diabetic healthy control subjects. Serum Malondialdehyde (MDA) Myeloperoxidase (MPO), Total antioxidants, (TAC) Superoxide dismutase (SOD), Catalase (CAT) and Total cholesterol, (TC), HDL cholesterol (HDL-C), Triglycerides (TG) were estimated spectrophotometrically. A comet assay was employed to evaluate DNA damage. Type 2 diabetic subjects had higher levels of plasma MDA and MPO concentration, but lower TAC, GSH, CAT and SOD activity. Correlation analysis shows that there is a positive association between MPO and MDA concentration but negative correlations with TAC status and SOD activity to the fasting blood glucose level and duration of diabetes. The comet assay revealed higher percentage of DNA damage in diabetics when compared to control subjects. The results of our present study suggests that hyperglycemia in diabetic subjects is the predominant cause for oxidative stress over antioxidant defense systems leading to lipid peroxidation and oxidative DNA damage which possibly contribute to the development of diabetes and its complications