Divya Arora

Polysaccharides based nanomaterials for targeted anti-cancer drug delivery

Abstract Polysaccharides, an important class of biological polymers, are effectively bioactive, nontoxic, hydrophilic, biodegradable and offer a wide diversity in structure and properties. These can be easily modified chemically and biochemically to enhance the bioadhesion with biological tissues, better stability and can improve bioavailability of drugs. Most of the chemotherapeutic drugs have a narrow therapeutic index, slow drug delivery systems and poor water solubility that usually proves toxic to human bodies. The inherent biocompatibility of these biopolymers have shown enhancement of solubility of some chemotherapeutic drugs which also leads to the preparation of nanomaterials for the delivery of antibiotics, anticancer, proteins, peptides and nucleic acids using several routes of administration. Recently, synthesis and research on polysaccharides based nanomaterials have gained enormous attention as one of the most applicable resources in nanomedicine area. This review article will provide a specific emphasis on polysaccharides as natural biomaterials for targeted anticancer drug delivery system.

Isolation and characterization of bioactive metabolites from Xylaria psidii, an endophytic fungus of the medicinal plant Aegle marmelos and their role in mitochondrial dependent apoptosis against pancreatic cancer cells

BACKGROUND The genus Xylaria has been reported as a rich source of biologically active secondary metabolites. In the present study, an endophytic fungus Xylaria psidii has been isolated from the leaf sample of Aegle marmelos (L.) Corr., characterized on the basis of its morphological features and sequence data for the ITS region (KU291350) of the nuclear ribosomal DNA. Biological screening of ethyl acetate extract of Xylaria psidii displayed a potential therapeutic effect on pancreatic cancer cells. HYPOTHESIS This study was designed systematically to explore Xylaria psidii, an endophytic fungus for the identification of biologically active secondary metabolites against pancreatic cancer cells. METHODS While exploring the bioactive secondary metabolites, a sensitive and reliable LC-MS based dereplication approach was applied to identify four compounds A-D from fungal extract. Further bioactivity guided isolation of fungal extract yielded two major metabolites 1 and 2. The structures of 1 and 2 have been determined by detailed spectroscopic analysis including MS, NMR, IR and UV data and similarity with published data. Xylarione A (1) is new whereas (-) 5-methylmellein (2) is reported for the first time from X. psidii. Both the isolated compounds were screened for their effect on the viability and proliferation against a panel of cancer cell lines (MCF-7, MIA-Pa-Ca-2, NCI-H226, HepG2 and DU145) of different tissue origin. RESULTS Compounds 1 and 2 exhibited cytotoxicity against pancreatic cancer (MIA-Pa-Ca-2) cells with IC50 values of 16.0 and 19.0 µm, respectively. The cell cycle distribution in MIA-Pa-Ca-2 cells, confirmed a cell cycle arrest at the sub-G1 phase. Cell death induced by 1 and 2 displayed features characteristic of apoptosis. Flow cytometry based analysis of 1 and 2 using Rhodamine-123 displayed substantial loss of mitochondrial membrane potential in a concentration dependent manner by both the compounds. CONCLUSION Results conclude that the isolated compounds 1 and 2 are responsible for the activity shown by crude ethyl acetate extract and may act as potential leads for medicinal chemists for designing more potent analogs.

An update on polysaccharide-based nanomaterials for antimicrobial applications

Scientific community has made a lot of efforts to combat the infectious diseases using antimicrobial agents, but these are associated with problems of development of multi-drug resistance and their adverse side effects. To tackle these challenges, nanocarrier-based drug delivery system using polysaccharides has received enormous attention in the past few years. These antimicrobial agents can become more efficacious when adsorbed, entrapped, or linked to polysaccharides. In addition, these nanocarrier-based systems provide an increase in the surface area of the drug and are able to achieve the targeted drug delivery as well as used for the synthesis of packaging materials with improved mechanical strength, barrier, and antimicrobial properties. This review focuses on potential therapeutic applications of nanocarrier-based drug delivery systems using polysaccharides for antimicrobial applications.

Preparation, characterization and toxicological investigation of copper loaded chitosan nanoparticles in human embryonic kidney HEK-293 cells

Metallic nanoparticles often attribute severe adverse effects to the various organs or tissues at the molecular level despite of their applications in medical, laboratory and industrial sectors. The present study highlights the preparation of copper adsorbed chitosan nanoparticles (CuCSNPs), its characterization and validation of cytotoxicity in human embryonic kidney HEK-293 cells. Particle size of the CuCSNPs was determined by using Zetasizer and the copper loading was quantified with the help of ICP/MS. Further characterization of CuCSNPs was carried out by FT-IR analysis to determine the formation of nanoparticles and SEM was conducted for the morphological analysis of the CuCSNPs. The CuCSNPs exhibited pronounced cytotoxic effects towards HEK-293 cells as analyzed by MTT assay. Moreover, the CuCSNPs inhibited the colony formation and induced nuclear damage at the dose of 100 μg/mL, much more effectively than the in built control copper sulfate (CuSO4). At the molecular level, the CuCSNPs were found to be triggering reactive oxygen species (ROS), activating effector caspases and subsequent PARP cleavage to induce cell death in HEK-293 cells.

Recent advances in near-infrared light-responsive nanocarriers for cancer therapy

In recent years, research has focused on the development of smart nanocarriers that can respond to specific stimuli. Among the various stimuli-responsive platforms for cancer therapy, near-infrared (NIR) light (700-1000nm)-responsive nanocarriers have gained considerable interest because of their deeper tissue penetration capacity, precisely controlled drug release, and minimal damage towards normal tissues. In this review, we outline various therapeutic applications of NIR-responsive nanocarriers in drug delivery, photothermal therapy (PTT), photodynamic therapy (PDT), and bioimaging. We also highlight recent trends towards NIR-responsive combinatorial therapy and multistimuli-responsive nanocarriers for improving therapeutic outcomes.

Therapeutic applications of resveratrol nanoformulations

Resveratrol, or 3, 5, 4-trihydroxy-trans-stilbene, is a naturally occurring polyphenol present in several dietary sources such as grapes, soybeans, berries, pomegranate and peanuts. Resveratrol has received recent attention due to its diverse pharmacological activities. However, resveratrol clinical efficacy is limited due to its poor systemic bioavailability, of less than 1%, which is due to its low aqueous solubility, extensive first-pass metabolism and existence of enterohepatic recirculation. Therefore, in order to overcome these limitations, various nanocarriers including polymeric nanoparticles, solid lipid nanoparticles, liposomes, micelles and conjugates have been developed. These nanocarriers are able to enhance the bioavailability of resveratrol by modulating the P-glycoprotein, cytochrome P-450 enzymes and bypassing the hepatic first-pass effect. Here we review resveratrol nanoformulations for enhancing the efficacy of native resveratrol.

Bacillus amyloliquefaciens induces production of a novel blennolide K in coculture of Setophoma terrestris

The discovery of known bioactive chemical leads from microbial monocultures hinders the efficiency of drug discovery programmes. Therefore, in recent years, the use of fungal–bacterial coculture experiments has gained considerable attention due to their ability to generate new bioactive leads. In this work, fungal strain Setophoma terrestris was cocultured with Bacillus amyloliquifaciens to discover novel bioactive compounds.

Therapeutic applications of betulinic acid nanoformulations

Betulinic acid (BA), a naturally occurring plant‐derived pentacyclic triterpenoid, has gained attention in recent years owing to its broad‐spectrum biological and medicinal properties. Despite the pharmacological activity of BA, it has been associated with some drawbacks, such as poor aqueous solubility and short half‐life in vivo, which limit therapeutic application. To solve these problems, much work in recent years has focused on enhancing BAs aqueous solubility, half‐life, and efficacy by using nanoscale drug delivery systems. Several different kinds of nanoscale delivery systems—including polymeric nanoparticles, magnetic nanoparticles, liposomes, polymeric conjugates, nanoemulsions, cyclodextrin complexes, and carbon nanotubes—have been developed for the delivery of BA. Here, we focus on the recent developments of novel nanoformulations used to deliver BA in order to improve its efficacy.

Nanocarriers for Resveratrol Delivery

There is a current interest in phytoalexin resveratrol due to its vast therapeutic effects such as anti-cancer, anti-viral, anti-amyloid antioxidant, anti-aging, anti-inflammatory, cardio and neuroprotection. Resveratrol, of chemical name 3,5,4-trihydroxy-trans-stilbene, is a naturally occurring polyphenol, which is present in several dietary sources such as grapes, soybeans, berries, pomegranate and peanuts. However, resveratrol clinical efficacy is limited due to its poor systemic bioavailability, of less than 1%, which is due to its low aqueous solubility, extensive first pass metabolism and existence of enterohepatic recirculation. To overcome these limitations various nanocarriers including polymeric nanoparticles, solid lipid nanoparticles, liposomes, micelles, and conjugates have been developed. These nanocarriers enhance the bioavailability of resveratrol due to their ability to modulate the P-glycoprotein (P-gp), cytochrome P-450 enzymes, and bypassing the hepatic first-pass effect. This chapter presents recent advances in application of nanocarriers to deliver resveratrol for modulating its pharmacokinetics and clinical efficacy.

Cyclodextrin-Based Carriers for Delivery of Dietary Phytochemicals

The food and pharmaceutical industry is searching for innovative solutions to enhance the bioavailability and clinical efficacy of dietary phytochemicals. In this regard, cyclodextrins have gained widespread attention as functional excipients. Numerous studies have demonstrated that cyclodextrin inclusion complexes enhance apparent water solubility, physico-chemical stability and improve the bioavailability of the dietary phytochemicals. In addition, dual encapsulation, that is the complexation of dietary molecules with cyclodextrins followed by encapsulation into nanomaterials such as liposomes, nanoparticles, conjugates, has also been investigated. Here, we review the applications of natural and chemically modified cyclodextrins for the delivery of dietary phytochemicals. We focus mainly on outcomes of inclusion complexes for enhancing solubility, bioavailability and efficacy of the delivered phytochemicals. We also discuss recent trends in dual-encapsulation.