Tragacanth gum-based nano-nutraceuticals synthesis by encapsulation of beetroot juice and Ocimum basilicum leaves for micronutrient deficient population.

Micronutrient deficiencies, such as iron, folic acid, and vitamins C and D, are currently prevalent due to inadequate consumption of natural food sources, namely raw vegetables and fruits. This deficiency is compounded by the growing reliance on synthetic nutraceuticals and processed food, which exhibit poor absorbency within the gastrointestinal tract. Scientific studies consistently indicate that naturally prepared whole foods are superior in terms of nutrient absorption compared to processed and synthetic supplements. To address this issue, we utilized FDA-approved tragacanth gum (TG) in the synthesis of nano-nutraceuticals by encapsulating beetroot juice and ball-milled sweet basil (Ocimum basilicum). TG, in its micro or macro form, possesses the remarkable ability to form hydrogels capable of absorbing water up to 50 times its weight. However, the hydrogel-forming property diminishes when TG is reduced to the nanoscale. We effectively exploited these properties to facilitate the synthesis of nano-nutraceuticals. The procedure involved encapsulating beetroot juice and sweet basil nanopowder using TG hydrogel, followed by freeze-drying. Subsequently, the freeze-dried encapsulated TG composite was subjected to ball-milling to achieve the desired nano-nutraceuticals. These nano-nutraceuticals naturally contain essential nutrients such as iron, folic acid, ascorbic acid, chlorophyll, niacin, and sugars, without the need for chemical processing or preservatives.

Redox responsive xylan-SS-curcumin prodrug nanoparticles for dual drug delivery in cancer therapy.

Chemotherapeutic agents with different anticancer mechanisms could enhance therapeutic effect in cancer therapy by their combined application. In this study, redox-sensitive prodrug nanoparticles based on Xyl-SS-Cur conjugate were developed for co-delivery of curcumin and 5-FU in cancer therapy. The Xyl-SS-Cur conjugate was synthesized via covalent conjugation of curcumin to xylan through a disulphide (-S-S-) linkage. The Xyl-SS-Cur conjugate could self-assemble in aqueous medium into nanoparticles and the lipophilic 5-fluorouracil-stearic acid (5-FUSA) prodrug was encapsulated into the hydrophobic core of Xyl-SS-Cur NPs through dialysis membrane method. The obtained Xyl-SS-Cur/5-FUSA NPs had an appropriate size (∼217 ±â€¯2.52 nm), high drug loading of curcumin (∼ 31.4 wt%) and 5-FUSA (∼ 11.8 wt%) and high stability. The interaction of Xyl-SS-Cur/5-FUSA NPs with blood components was investigated by hemolysis study. The cytotoxicity study demonstrated that Xyl-SS-Cur/5-FUSA NPs induced higher cytotoxicity than free drugs against the Human colorectal cancer cells (HT-29, HCT-15). These results indicate that Xyl-SS-Cur/5-FUSA NPs can serve as a promising drug delivery system in cancer therapy.

pH-responsive prodrug nanoparticles based on xylan-curcumin conjugate for the efficient delivery of curcumin in cancer therapy.

In the present study, novel pH-responsive prodrug nanoparticles based on xylan-curcumin (xyl-cur) conjugate were developed to enhance the therapeutic efficacy of curcumin in cancer therapy. The synthesis of xyl-cur conjugate (prodrug) was confirmed by FT-IR, 1H NMR, UV-vis and fluorescence spectroscopy. The xyl-cur prodrug was subsequently self-assembled in to nanoparticles (xyl-cur prodrug NPs) in an aqueous medium with the average particle size 253 nm and the zeta potential of -18.76 mV. The xyl-cur prodrug NPs were highly pH-sensitive in nature and most of the drug was released at lower pH. The interaction of the xyl-cur prodrug NPs with blood components was tested by hemolysis study. The cytotoxic activity of the xyl-cur prodrug NPs against human colon cancer cells (HT-29, HCT-15) demonstrated that the prodrug NPs exhibits greater cytotoxic effect than curcumin. Therefore, these results reveal that xyl-cur prodrug NPs could be a promising candidate for improving the intracellular delivery of curcumin in cancer therapy.

Prodrug encapsulated albumin nanoparticles as an alternative approach to manifest anti-proliferative effects of suicide gene therapy.

Conventional anticancer agents are associated with limited therapeutic efficacy and substantial nonspecific cytotoxicity. Thus, there is an imminent need for an alternative approach that can specifically annihilate the cancer cells with minimal side effects. Among such alternative approaches, CD::UPRT (cytosine deaminase uracil phosphoribosyl transferase) suicide gene therapy has tremendous potential due to its high efficacy. Prodrug 5-Fluorocytosine (5-FC) used in combination with CD::UPRT suicide gene suffers from limited solubility which subsequently leads to decline in therapeutic efficacy. In order to overcome this, 5-FC encapsulated bovine serum albumin nanoparticles (BSA-5-FC NPs) were prepared in this work by desolvation method. Physico-chemical characterizations studies revealed amorphous nature of BSA-5-FC NPs with uniform spherical morphology. Apart from increase in solubility, encapsulated 5-FC followed slow and sustained release profile. Suicide gene expressing stable clone of L-132 cells were adapted for investigating therapeutic potential of BSA-5-FC NPs. These nanoparticles were readily taken up by the cells in a concentration dependent manner and subsequently manifested apoptosis, which was further confirmed by morphological examination and gene expression analysis. These findings clearly illustrate that CD::UPRT suicide gene therapy can be efficiently utilized in combination with this nanosystem for improved suicide gene therapy and tumor eradication.

Studies on Brahma rasayana in male swiss albino mice: Chromosomal aberrations and sperm abnormalities.

Ayurveda, the Indian holistic healthcare system encompasses traditional medicines with a principle of creating harmony and maintaining balance within the natural rhythms of the body. Rasayana is one of the branches of Ayurveda frequently used as rejuvenant therapy to overcome many discomforts and prevent diseases. It has been reported that rasayanas have immunomodulatory, antioxidant and antitumor functions. However, the genotoxic potential of many rasayanas remains to be evaluated. The present study was undertaken to assess the role of Brahma rasayana(BR) on genotoxicity in vivo in a mouse test system. The older mice (9 months) were orally fed with rasayana for 8 weeks. The treated groups showed no signs of dose-dependent toxicity at the dosage levels tested. The body weight loss/gain and feed consumption were unaffected at tested doses. Furthermore, sperm abnormalities and chromosomal aberrations were insignificant in the treatment group when compared to controls. However, there was a marginal increase in sperm count in the BR treated animals. These findings clearly indicate that there are no observed adverse genotoxic effects elicited by BR in experimental animals such as mice.

Implication of functional activity for determining therapeutic efficacy of suicide genes in vitro.

Gene-Directed Enzyme Prodrug Therapy (GDEPT), commonly known as suicide gene therapy, provides a selective approach to eradicate tumor cells that is currently considered as an alternate approach to conventional therapy for cancers due to its high efficacy. Herein, we have demonstrated functional activity of the cytosine deaminase (CD) and the hybrid cytosine deaminase-uracil phosphoribosyltransferase (CD-UPRT) suicide genes in transfected cell lines. We have monitored retention profiles of various metabolites that were formed during enzymatic conversion of the prodrug 5-flurocytosine (5-FC) using reverse phase HPLC method. Therapeutic effect of suicide genes was established by cell viability and toxicity assay, whereas apoptotic induction was confirmed by DNA fragmentation ELISA. Our results demonstrated that 5-FC/CD-UPRT-mediated apoptotic cell death was more than 5-FC/CD, which could be further potentiated with anticancer compound curcumin. Such results corroborated 5-FC/CD-UPRT in combination with curcumin as a better chemosensitization method.

Apoptotic induction with bifunctional E.coli cytosine deaminase-uracil phosphoribosyltransferase mediated suicide gene therapy is synergized by curcumin treatment in vitro.

Development of novel suicide gene therapy vector with potential application in cancer treatment has a great impact on human health. Investigation to understand molecular mechanism of cell death is necessary to evaluate the therapeutic application of suicide vectors. For example, the bifunctional E.coli cytosine deaminase & uracil phosphoribosyltransferase fusion (CD-UPRT) gene expression is known to sensitize a wide range of cells toward nontoxic prodrug 5-flurocytosine (5-FC) by converting it to toxic compounds, but the exact pathway of cell death is yet to be defined. Herein, we investigated the mechanism of cell death by 5-FC/CD-UPRT suicide system in both cancer and non-cancer cells and found that the optimum 5-FC concentration led to programmed cell death in vitro. The CD-UPRT expression of transfected cells was measured by the RT-PCR analysis. Biochemical assays, such as mitochondrial activity (MTS) and lactate dehydrogenase (LDH) measurements exhibited cell death. Microscopic experiments showed characteristic onset of apoptosis which was further supported by internucleosomal DNA cleavage of BrdU labeled cellular DNA, appearance of characteristic laddering of chromosomal DNA and involvement of caspase pathway. Furthermore, the 5-FC/CD-UPRT-mediated apoptosis was potentiated with addition of a known anticancer agent curcumin. Our in vitro studies confirmed synergistic induction of apoptotic pathway in the combination treatment. Therefore, combination of 5-FC/CD-UPRT with curcumin could be a potential chemosensitization strategy for cancer treatment.

Effect of Spirulina fusiformis on cyclophosphamide and mitomycin-C induced genotoxicity and oxidative stress in mice.

Spirulina fusiformis was tested for its possible in vivo protective effects against cyclophosphamide (CP) and mitomycin-C (MMC) induced genotoxicity and oxidative stress in mice. Pre-treatment with S. fusiformis (250, 500 and 1000 mg kg(-1), p.o., daily for 5 days) significantly reduced the chromosomal damage and lipid peroxidation with concomitant changes in antioxidants and detoxification systems. All the three tested doses were effective in exerting a protective effect against CP and MMC.

Inhibition of genotoxicity by saffron (Crocus sativus L.) in mice.

Experiments were carried out to ascertain whether or not saffron (dried stigmas of Crocus sativus L.), a commonly used agent for flavoring and coloring food can exert modulatory effects on the in vivo genotoxicity of cisplatin (CIS), cyclophosphamide (CPH), mitomycin C (MMC) and urethane (URE). For this purpose, Swiss albino mice were pretreated for five consecutive days with three doses (20, 40 and 80 mg/kg body weight) of the aqueous extract of saffron. Genotoxic effects were assessed in the mouse bone marrow micronucleus test. The results obtained suggest that pretreatment with saffron can significantly inhibit the genotoxicity of CIS, CPH, MMC and URE. This inhibitory effect was not always dose-dependent. In addition, the hepatic glutathione S-transferase (GST) activity was assessed in the control and treated animals. No significant change in GST activity was observed after pretreatment with saffron alone. Treatment with the genotoxins alone significantly inhibited GST activity. Saffron pretreatment attenuated the inhibitory effects of the genotoxins on GST activity.