Nano-emulsomes for back of the eye delivery of Ganciclovir: formulation optimization, characterization & in vitro/in vivo evaluation.

In this work, novel carriers- nanoemulsomes (NE) of ganciclovir (GCV) and a fluorescent marker sodium fluorescein (SF) were developed and evaluated for posterior ocular delivery via topical route. GCV loaded emulsomes (GCV NE) were optimized by a factorial design and various characterization parameters were performed on the optimized batch. The optimized batch had particle size of 131.04 ± 1.87 nm, % entrapment efficiency of 36.42 ± 3.09% and its TEM image showed discrete spherical structures below 200 nm. Ocular irritation potential of excipients and formulation were evaluated by cell line based in vitro tests on SIRC cell line, results confirmed the safety of excipients for ocular use. Precorneal retention and pharmacokinetic studies of GCV NE were performed in rabbit eyes which showed significant retention of GCV NE in the cul-de-sac. The ocular distribution study of SF-loaded nanoemulsomes (SF NE) were performed in mice eyes by confocal microscopy, images showed fluorescence in the various internal layers of retina, suggesting efficacy of emulsomes in delivering agents to the back of eye via topical administration.

Topical instillation of triamcinolone acetonide-loaded emulsomes for posterior ocular delivery: statistical optimization and in vitro-in vivo studies.

The objective of the present investigation was to formulate and characterize a novel lipid-based carrier-emulsomes loaded with triamcinolone acetonide (TA)/Nile red (NR) for non-invasive delivery to the posterior segment of the eye upon topical application. To optimize and delineate the effect of independent variables on dependent variables, Box-Behnken design (BBD) was adopted. The optimized batch was characterized for size, zeta potential, surface morphology by transmission electron microscopy, drug-excipient interaction by differential scanning calorimetry, osmolarity, pH, ex vivo transcorneal permeation, and stability studies. A short-term exposure (STE) test was performed on Statens Seruminstitut Rabbit Corneal (SIRC) cell lines to evaluate the in vitro ocular irritation. Precorneal retention study was performed in rabbit eyes. Confocal microscopy was used for ocular distribution studies in mice eye by preparing dye (Nile red)-loaded formulations. The surface response and contour plots along with ANOVA results demonstrated an interaction between the factors. The optimized batch had particle size of 131.17 ± 3.17 nm and entrapment efficiency of 71.56 ± 4.19%. TEM image showed unimodal, nano-sized emulsomes. TA-loaded emulsomes exhibited higher transcorneal permeation as compared to drug solution. In vitro irritation studies confirmed the safety of excipients for ophthalmic use. Fluorescence microscopic images obtained after ocular distribution studies showed strong fluorescence in inner and outer plexiform layers of the retina in comparison to dye solution confirming the delivery of dye to the posterior segment of mice eye after topical ocular instillation. Graphical abstract.

A novel nanoparticles impregnated ocular insert for enhanced bioavailability to posterior segment of eye: In vitro, in vivo and stability studies.

The present investigation was carried out to demonstrate with the help of in vitro and in vivo studies that nanoparticles impregnated ocular inserts effectively delivers significant concentration of drug to the posterior segment of eye after topical administration for treatment of glaucoma. Drug loaded Nanoparticles and their ocular insert have been reported to reduce side effects of orally administered Acetazolamide. Eudragit NPs were prepared by the solvent diffusion nanoprecipitation technique. The prepared NPs were evaluated for various parameters such as particle size, zeta potential, % entrapment efficiency, % drug loading, DSC, FTIR, TEM and stability studies. Ocular inserts of NPs were prepared by solvent casting method. The prepared ocular inserts were evaluated for thickness, content uniformity, folding endurance, disintegration time, morphology and stability study. The NPs and ocular inserts were evaluated for in-vitro drug diffusion study, ex-vivo trans-corneal permeability study, in-vivo ocular tolerability and intra ocular pressure (IOP) reduction study. The optimized batch was stable for a period of 3months in lyophilized form. The optimized formulations had size range of 367nm±8nm, zeta potential around +7mV±1.3mV and 51.61%±3.84% entrapment efficiency with 19%±1.40% drug loading. The ex-vivo trans-corneal study showed higher cumulative corneal permeation, flux across corneal tissue (2.460±0.028µg/ml) and apparent corneal permeability (3.926×10-6cm2/s & 3.863×10-6cm2/s) from drug loaded Eudragit NPs and Ocular inserts as compared to drug solution (0.671±0.020µg/ml & 3.166×10-6cm2/s). In-vivo study showed the Eudragit NPs and ocular insert produced significant (P<0.001) lowering in intra ocular pressure compared with the solution of free drug after 3h of topical ocular administration. Plain Eudragit NPs caused no inflammation and/or discomfort in rabbit eyes and neither affected the intra ocular pressure establishing their safety and non irritancy.

Protective role of standardized Feronia limonia stem bark methanolic extract against carbon tetrachloride induced hepatotoxicity.

OBJECTIVE: This study evaluates hepatoprotective potential of Feronia limonia stem bark (FSB) extracts and fractions using experimental models. MATERIALS AND METHODS: Activity levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and cell viability were evaluated in HepG2 cells treated with carbon tetrachloride (CCl4) in presence or absence of FL extracts or fractions. Also, plasma markers of hepatic damage, hepatic antioxidants, lipid peroxidation and histopathological alterations were assessed in rats treated with CCl4 alone or in combination with 200 or 400 mg/kg bodyweight (BW) of FSB-7 or 25 mg/kg BW of silymarin. RESULTS: In vitro co-supplementation of FSB extracts or fractions recorded varying degree of hepatoprotective potentials. Also, pre-supplementation of FSB methanolic extract (FSB-7) followed by CCl4 treatment significantly prevented hepatic damage and depletion of cellular antioxidants. Also, CCl4+ FSB-7 group showed minimal distortion in the histoarchitecture of liver and results were comparable to that of CCl4+ silymarin treated rats. CONCLUSION: This inventory is the first scientific report on hepatoprotective potential of FSB methanolic extract.

Hepatoprotective potential of Tecomella undulata stem bark is partially due to the presence of betulinic acid.

ETHNOPHARMACOLOGICAL RELEVANCE: Tecomella undulata (TU;` Family Bignoniaceae) is used in Indian Ayurvedic system of medicine for treating various diseases including hepatic ailments. It is also incorporated in various marketed hepatoprotective polyherbal formulations. AIM: The present study was aimed at evaluating possible hepatoprotective role of isolated compounds from TU stem bark (TSB) using in vitro and in vivo experimental models. METHODS: In vitro cytotoxicity and hepatoprotective potential of various extract, fractions and isolated compounds from TU stem bark were evaluated using HepG2 cells. Rats were pre-treated with TU methanolic extract (TSB-7) or betulinic acid (MS-2) or silymarin for 7 days followed by a single dose of CCl(4) (0.5 ml/kg, i.p.). Plasma markers of hepatic damage, hepatic antioxidants and indices of lipid peroxidation along with microscopic evaluation of liver were assessed in control and treatment groups. RESULTS: TSB-2 and MS-1 accounted for significant cell death whereas; TSB-1, TBS-7, TSB-9, TSB-10 and, MS-2 did not register significant cytotoxicity. Further, non-cytotoxic components exhibited ascending grade of hepatoprotection in vitro (TSB-10

Hepatoprotective activity of Feronia limonia root.

OBJECTIVES: The aim of this study was to evaluate the hepatoprotective potential of a methanolic extract and of marmesin isolated from the root bark of Feronia limonia. METHODS: Activity levels of aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), cell viability and cell death were evaluated in HepG2 cells (human liver hepatoma cells) treated with CCl4 in the presence or absence of F. limonia extract or marmesin. Plasma activity levels of AST, ALT, bilirubin, alkaline phosphatase, protein, hepatic antioxidants, lipid peroxidation and histopathological evaluations were carried out in rats treated with CCl4 alone or co-supplemented with F. limonia extract or marmesin in a dose-dependent manner. KEY FINDINGS: In-vitro co-supplementation of F. limonia methanolic extract or marmesin significantly minimized alteration in levels of AST and ALT and improved cell viability. Oral administration of F. limonia methanolic extract or marmesin significantly prevented CCl4-induced elevation in the plasma markers of hepatic damage and hepatic lipid peroxidation and a decrease in hepatic antioxidants. In-vivo hepatoprotective potential of F. limonia methanolic extract and marmesin was evident from the minimal alterations in the histoarchitecture of liver. CONCLUSIONS: This has been the first scientific report on the hepatoprotective potential of F. limonia root bark methanolic extract and marmesin.

Amelioration of carbon tetrachloride induced hepatotoxicity in rats by standardized Feronia limonia. Linn leaf extracts.

The hepatoprotective potential of standardized Feronia limonia (Family, Rutaceae) methanolic extract (FL-7) and chloroform soluble fraction (FL-9) were assessed against carbon tetrachloride (CCl4) induced oxidative stress and hepatotoxicity in rats. Rats treated with CCl4 recorded significant elevation in plasma markers of hepatic injury, alteration in hepatic antioxidant status and histopathological damages. However, rats pretreated with FL-7 (200 or 400 mg/kg, p.o.) and FL-9 (100 or 200 mg/kg, p.o.) for 7 days and later administered CCl4 (0.5 ml/kg, i.p.) recorded lowered indices of the above mentioned parameters and minimal histological damage in a dose dependent manner. These results were comparable to that of CCl4+silymarin treated rats. The results obtained with FL-7 and FL-9 are attributable to their free radical scavenging potential due to high contents of polyphenols and flavonols recorded herein. Overall, this study establishes the efficacy of FL-7 and FL-9 as hepatoprotective agents against CCl4 induced hepatotoxicity in rats.

Traditional uses, phytochemistry and pharmacology of Tecomella undulata- A review

The aim of the present review is to present comprehensive information of the traditional uses, phytochemistry and pharmacology of Tecomella undulata (Family, Bignoniaceae) and to discuss future scope of research. Tecomella undulata (TU) is commonly known as desert teak (ver. Rohiro) and is traditionally for treating liver and spleen diseases, tumours, conjunctivitis, hepatosplenomegaly, syphilis, gonorrhea, hepatitis, as a blood purifier and in wound healing. Compounds such as naphthaquinone derivative, iridoid glucoside, phytosterol, fatty alcohol, flavonols, flavonoid glucoside and triterpenoids have been reported from TU. Anti HIV, anti bacterial, anti microbial, immune modulator, analgesic and hepatoprotective activities have been reported from its various aerial parts. In the present review, attempts have been made to compile research reports on TU, to assess current research trends with possible future avenues of research.

Standardization of Feronia limonia L. leaves by HPLC, HPTLC, physico-chemical and histological parameters / Estandarización de hojas de Feronia limonia L. por HPLC, HPTLC, parámetros fisicoquímicos e histológicos

Feronia limonia (Family Rutaceae, subfamily Aurantioideae), commonly known as kaitha or wood apple, is widely used as an ethnomedicine in India. Its leaves are prescribed for a wide variety of ailments like diarrhoea, urinary disorders, treatment of piles or haemorrhoids, acidity, ulcers, ringworm and other chronic skin infections. However, detailed scientific information is not available to identify the plant material and to ascertain its quality and purity. In the present communication, a qualitative fingerprinting of Feronia limonia (FL), extracts have been performed by HPTLC and HPLC methods, which provide qualitative insights into the bioactive constituents present in the extracts. Also, morphological anatomical and physico-chemical characters, along with phytochemical screening and fluorescence analysis of powdered crude drug were carried out for systemic identification and authentification of leaves. This study provides referential information for identification and characterization of FL leaf and its extracts.

Feronia limonia (Familia Rutaceae, subfamilia Aurantioideae), comúnmente conocida como kaitha o manzana de madera, y es extensamente usada como una ethnomedicina en India. Sus hojas son indicadas para una amplia variedad de dolencias como diarrea, desórdenes urinarios, el tratamiento de hemorroides, acidez, úlceras, tiña y otras infecciones crónicas de la piel. Sin embargo, la información científica detallada no está disponible para identificar el material de la especie y averiguar su calidad y pureza. En la presente comunicación, un análisis cualitativo de extractos de Feronia limonia (FL), se realizó por HPTLC y HPLC, lo que proporcionó información cualitativa de los componentes bioactivos presentes en los extractos. También, los caracteres anatómicos, fisico-químicos y morfológicos, junto con un examen fitoquímico y análisis de fluorescencia de la planta en polvo fueron realizados para la identificación sistémica y autentificación de las hojas. Este estudio proporciona la información de referencia para identificación y caracterización de las hojas de FL y sus extractos.

Cytotoxicity evaluation and hepatoprotective potential of bioassay guided fractions from Feronia Limmonia Linn leaf.

OBJECTIVE: To evaluate the cytotoxicity and hepatoprotective potentials of extracts, fractions or isolated compound from the leaves of Feronia limonia (F. limonia). METHODS: Qualitative phytochemical analysis of extracts, fractions or compound was performed by means of thin layer chromatography and spectroscopic assays. The % purity of compound was measured by analytical HPLC. Extracts, fractions or compound have been individually evaluated for their cytotoxicity effects (10, 20, 100, 250, 500, 750 and 1 000 µg/mL). Based on the inhibitory concentration (IC50) obtained from the cell viability assay, graded concentrations of extracts, fractions or isolated compound were assessed (10, 20, 50, 100, 200 µg/mL) for its hepatoprotective potential against CCl4-induced hepatotoxicity by monitoring activity levels of serum glutamatic pyruvatic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT). RESULTS: Results indicated that the methanol extract of F. limonia was non-toxic and hepatoprotective in nature as compared with the petroleum ether extract. The acetone fraction of methanolic extract also showed similar properties but the subsequent two fractions were cytotoxic. However, the pure compound isolated from the penultimate fraction of methanolic extract was non-toxic and hepatoprotective in nature. Biochemical investigations (SGOT, SGPT) further corroborated these cytological observations. CONCLUSIONS: It can be concluded from this study that F. limonia methanol extract, some fractions and pure isolated compound herein exhibit hepatoprotective activity. However, cytotoxicity recorded in the penultimate fraction and investigation of structural details of pure compound warrants further study.