Enhanced EPR directed and Imaging guided Photothermal Therapy using Vitamin E Modified Toco-Photoxil.

Herein we report synthesis, characterization and preclinical applications of a novel hybrid nanomaterial Toco-Photoxil developed using vitamin E modified gold coated poly (lactic-co-glycolic acid) nanoshells incorporating Pgp inhibitor d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a highly inert and disintegrable photothermal therapy (PTT) agent. Toco-Photoxil is highly biocompatible, physiologically stable PTT material with an average diameter of 130 nm that shows good passive accumulation (2.3% ID) in solid tumors when delivered systemically. In comparison to its surface modified counterparts such as IR780-Toco-Photoxil, FA-Toco-Photoxil or FA-IR780-Toco-Photoxil accumulation are merely ~0.3% ID, ~0.025% ID and ~0.005% ID in folate receptor (FR) negative and positive tumor model. Further, Toco-Photoxil variants are prepared by tuning the material absorbance either at 750 nm (narrow) or 915 nm (broad) to study optimal therapeutic efficacy in terms of peak broadness and nanomaterial's concentration. Our findings suggest that Toco-Photoxil tuned at 750 nm absorbance is more efficient (P = 0.0097) in preclinical setting. Toco-Photoxil shows complete passiveness in critical biocompatibility test and reasonable body clearance. High tumor specific accumulation from systemic circulation, strong photothermal conversion and a very safe material property in body physiology makes Toco-Photoxil a superior and powerful PTT agent, which may pave its way for fast track clinical trial in future.

Embelin - a drug of antiquity: shifting the paradigm towards modern medicine.

INTRODUCTION: Embelia ribes or Embelia tsjeriam-cottam, more commonly known as vidanga, is a type of ayurvedic medicine that has been used to treat various diseases for a number of years. Bright orange embelin -rich fruits have been well established as ethnomedicinals, for a number of years with their pharmacological actions attributed to their hydroxybenzoquinone active constituent. Embelin has become known specifically for its antihelminthic and contraceptive use. AREAS COVERED: This drug evaluation provides a historical summary of embelin along with its therapeutic use, phytochemistry and toxicology. Embelin's pharmacotherapeutical properties are also discussed along with its molecular targets. It is hoped that this article will help to draw the attention of researchers and biopharmaceutical companies to the untapped potential in bioprospection for the development of new drugs. EXPERT OPINION: Embelin is the only known non-peptide small-molecule X-linked inhibitor of the apoptosis protein (XIAP) - an anti-apoptotic protein considered a promising cancer therapeutic target. Embelin acts as an NF-κB blocker and potential suppressor of tumorigenesis. It also exhibits potent cytotoxic, antioxidant and cancer chemopreventive effects. Given the potential uses of embelin, it is recommended that further investigations take place to properly explore its pharmacological and clinical effects.

Chemopreventive and hepatoprotective effects of embelin on N-nitrosodiethylamine and carbon tetrachloride induced preneoplasia and toxicity in rat liver.

Embelin, an active constituent isolated from the fruits of Embelia tsjeriam cottam was investigated for its chemopreventive and hepatoprotective effects against N-nitrosodiethylamine (NDEA) induced liver preneoplasia or carbon tetrachloride (CCl4) induced liver damage. Rats received NDEA, 1 ppm/g b.w. in drinking water for 6 weeks or CCl4, 0.7 ml/kg i.p. once a week for 4 weeks and embelin 50 mg, 100 mg/kg b.w. orally prior, during and after exposure to NDEA/CCl4 for 20 or 5 weeks, respectively. Embelin treatment significantly prevented NDEA or CCl4 induced increase in biochemical marker enzymes: glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase, glutathione-S-transferase, lipid peroxidase as well as hypoproteinemia, hypoalbuminuria and glutathione depletion. This was further substantiated by marked decrease in incidence of preneoplastic foci, and inflammatory cells on histopathological and transmission electron microscopic analysis. The present study suggests embelin is a promising chemopreventive and hepatoprotective agent.

Sida rhombifolia ssp. retusa seed extract inhibits DEN induced murine hepatic preneoplasia and carbon tetrachloride hepatotoxicity.

Sida rhombifolia ssp. retusa is a well established drug in the Ayurvedic system of medicine used for antirheumatism and antiasthmatism. Inhibitory effects of S. rhombifolia ssp. retusa seed extract on DEN induced hepatocellular preneoplastic foci and carbon tetrachloride (CCl4) induced hepatotoxicity was investigated in rats. Rats received DEN, 1ppm/g b.w. in drinking water for 6 weeks or CCl(4), 0.7 ml/kg i.p. once a week for 4 weeks and seed extract 50 mg, 100 mg/kg b.w. orally prior, during and after exposure to DEN/CCl4 for 20 or 5 weeks, respectively. Treatment with seed extract significantly inhibited the increase in DEN/CCl(4) induced activities of pre-cancerous marker enzymes; gamma-glutamyl transpeptidase, glutathione-S-transferase, hepatotoxicity marker enzymes; glutamate pyruvate transaminase, glutamate oxaloacetate transaminase and alkaline phosphatase as well as lipid peroxidase. Depleted glutathione, protein and albumin levels were restored. Also, histopathological and transmission electron microscopic studies showed prevention of cellular degenerative changes. The chemopreventive and hepatoprotective potentials of seed extract are due to free radical scavenging activity and restoration of cellular structural integrity.