pH-sensitive nanoparticles of enhanced epigallocatechin-3-gallate in colorectal cancer therapy.

Aim: Encapsulating epigallocatechin-3-gallate (EGCG) in pH-sensitive polymeric nanoparticles for targeted delivery of drugs could revolutionize colorectal cancer treatment. Materials & methods: Nanoparticles were synthesized to release drugs at colon pH. Dynamic light scattering measured their average diameter and ζ-potential, while differential scanning calorimetry and x-ray diffraction assessed EGCG encapsulation. Results: The nanoparticles showed stability and bioavailability in the gastrointestinal tract, efficiently encapsulating and releasing over 93% of EGCG at pH 7.2. They enhanced cytotoxicity against HT-29 cells and demonstrated antibacterial properties, increasing apoptosis and cell cycle arrest. Conclusion: The study underscores the potential of nanoparticles in enhancing EGCG delivery for colorectal cancer therapy, aiming to minimize side effects and improve therapeutic outcomes.

HPLC Estimation, Ex vivo Everted Sac Permeability and In Vivo Pharmacokinetic Studies of Darunavir.

Darunavir ethanolate (DRV) is an efficient protease inhibitor (PI) used in the treatment of human immunodeficiency virus (HIV) type-1 patients. An isocratic reversed-phase HPLC method was developed to monitor concentration of darunavir in in vitro intestinal fluid samples in everted sac absorption model in the presence of bioenhancers, viz., piperine, quercetin, naringenin. The method was validated and successfully applied to everted sac and pharmacokinetic studies in rats. The absorption profiles of DRV and apparent permeability coefficients were determined. The proposed method was found to be simple, rapid, robust and selective and was applied for continuous ex vivo monitoring of DRV in everted sac absorption studies. Of the three bioenhancers screened at different concentrations, piperine caused highest and significant 1.5-fold increase in apparent permeability of DRV across everted sac tissue. Further, co-administration of piperine significantly increased the maximum plasma concentration of DRV by 1.18-fold confirming the enhancement in its absorption.

Phytochemicals and PI3K Inhibitors in Cancer-An Insight.

In today's world of modern medicine and novel therapies, cancer still remains to be one of the prime contributor to the death of people worldwide. The modern therapies improve condition of cancer patients and are effective in early stages of cancer but the advanced metastasized stage of cancer remains untreatable. Also most of the cancer therapies are expensive and are associated with adverse side effects. Thus, considering the current status of cancer treatment there is scope to search for efficient therapies which are cost-effective and are associated with lesser and milder side effects. Phytochemicals have been utilized for many decades to prevent and cure various ailments and current evidences indicate use of phytochemicals as an effective treatment for cancer. Hyperactivation of phosphoinositide 3-kinase (PI3K) signaling cascades is a common phenomenon in most types of cancers. Thus, natural substances targeting PI3K pathway can be of great therapeutic potential in the treatment of cancer patients. This chapter summarizes the updated research on plant-derived substances targeting PI3K pathway and the current status of their preclinical studies and clinical trials.

Hydrophobic and electrostatic interactions between cell penetrating peptides and plasmid DNA are important for stable non-covalent complexation and intracellular delivery.

Cell penetrating peptides are useful tools for intracellular delivery of nucleic acids. Delivery of plasmid DNA, a large nucleic acid, poses a challenge for peptide mediated transport. The paper investigates and compares efficacy of five novel peptide designs for complexation of plasmid DNA and subsequent delivery into cells. The peptides were designed to contain reported DNA condensing agents and basic cell penetrating sequences, octa-arginine (R8 ) and CHK6 HC coupled to cell penetration accelerating peptides such as Bax inhibitory mutant peptide (KLPVM) and a peptide derived from the Kaposi fibroblast growth factor (kFGF) membrane translocating sequence. A tryptophan rich peptide, an analogue of Pep-3, flanked with CH3 on either ends was also a part of the study. The peptides were analysed for plasmid DNA complexation, protection of peptide-plasmid DNA complexes against DNase I, serum components and competitive ligands by simple agarose gel electrophoresis techniques. Hemolysis of rat red blood corpuscles (RBCs) in the presence of the peptides was used as a measure of peptide cytotoxicity. Plasmid DNA delivery through the designed peptides was evaluated in two cell lines, human cervical cancer cell line (HeLa) and (NIH/3 T3) mouse embryonic fibroblasts via expression of the secreted alkaline phosphatase (SEAP) reporter gene. The importance of hydrophobic sequences in addition to cationic sequences in peptides for non-covalent plasmid DNA complexation and delivery has been illustrated. An alternative to the employment of fatty acid moieties for enhanced gene transfer has been proposed. Comparison of peptides for plasmid DNA complexation and delivery of peptide-plasmid DNA complexes to cells estimated by expression of a reporter gene, SEAP. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Combination of ozonation with conventional aerobic oxidation for distillery wastewater treatment.

Laboratory-scale experiments were conducted in order to investigate the effect of ozone as pre-aerobic treatment and post-aerobic treatment for the treatment of the distillery wastewater. The degradation of the pollutants present in distillery spent wash was carried out by ozonation, aerobic biological degradation processes alone and by using the combinations of these two processes to investigate the synergism between the two modes of wastewater treatment and with the aim of reducing the overall treatment costs. Pollutant removal efficiency was followed by means of global parameters directly related to the concentration of organic compounds in those effluents: chemical oxygen demand (COD) and the color removal efficiency in terms of absorbance of the sample at 254 nm. Ozone was found to be effective in bringing down the COD (up to 27%) during the pretreatment step itself. In the combined process, pretreatment of the effluent led to enhanced rates of subsequent biological oxidation step, almost 2.5 times increase in the initial oxidation rate has been observed. Post-aerobic treatment with ozone led to further removal of COD along with the complete discoloration of the effluent. The integrated process (ozone-aerobic oxidation-ozone) achieved approximately 79% COD reduction along with discoloration of the effluent sample as compared to 34.9% COD reduction for non-ozonated sample, over a similar treatment period.

Ultrasound and ozone assisted biological degradation of thermally pretreated and anaerobically pretreated distillery wastewater.

The present work is aimed at increasing the overall efficiency of the treatment process of distillery spent wash using a combination of different treatment techniques. Initially the effluent samples were subjected to Thermal Pretreatment (TPT-DW) and anaerobic treatment (ANA-DW). Advanced oxidation techniques, viz., Ultrasound (US) and Ozone were then used for further COD reduction followed by the conventional aerobic oxidation using mixed microbial consortium. Pretreatment of TPT-DW with US and Ozone (as stand alone techniques) enhanced the subsequent aerobic oxidation rate. For US treated sample, a maximum of 13% COD reduction was attained at the end of 48 h of aerobic oxidation, while for the ozone treated effluent a maximum of 45.6% COD reduction was obtained as compared to mere 1.8% COD reduction for the control (TPT-DW directly subjected to aerobic oxidation) indicating a 25 times increase in the rate of aerobic biodegradation of ozonated sample. Anaerobically treated effluent sample (ANA-DW) could be successfully treated aerobically. In this case, however, the use of advanced oxidation techniques did not result in any synergistic effects. The rate of the aerobic oxidation was slightly higher for the control (ANA-DW directly subjected to aerobic oxidation) as compared to the sample pretreated using ultrasound or ozonation. TOC analysis revealed that between the two pretreatments studied, ozone was found to be superior over US as it led to both COD as well as TOC reduction during the aerobic oxidation step for ANA-DW effluent stream.

Enhancement in biodegradability of distillery wastewater using enzymatic pretreatment.

A combined treatment technique consisting of enzymatic hydrolysis, followed by aerobic biological oxidation was investigated for the treatment of alcohol distillery spent wash. The enzyme cellulase was used for the pretreatment step with an intention of transforming the complex and large pollutant molecules into simpler biologically assimilable smaller molecules. Batch experiments were performed in order to analyze the influence of various parameters like pretreatment time, enzyme concentration and pH during the pretreatment step on the subsequent aerobic oxidation kinetics. The rate of aerobic oxidation was enhanced by 2.3 fold for the pretreated sample as compared to the untreated sample when the pH during the pretreatment step was maintained at a value of 4.8. Similarly, a two fold increase in the aerobic oxidation rate was found when the effluent was pretreated with the enzyme, without any pH control (i.e. effluent pH of 3,8). The study indicated that the enzymatic pretreatment of the effluent could be one of the successful pretreatments which can lead to enhancement of the rate of the subsequent aerobic oxidation.

Ultrasound and enzyme assisted biodegradation of distillery wastewater.

Irradiation with ultrasound (US) and use of an enzyme (E) as pretreatment techniques were carried out to treat a complex effluent (distillery wastewater). These two techniques have been used alone as well as in combination and the efficacy of these techniques was tested by subjecting the effluent to subsequent aerobic biological oxidation (AO). When used alone, US exposure for 30 min and 2 h yielded the best COD reduction during the aerobic oxidation step (US+AO). For the enzyme when used alone, a pH value of 4.8 (corresponding to the optimum pH of the enzyme), a dose of 50 U and a pretreatment time of 24 h yielded better COD removal efficiency as compared to untreated effluent (aerobic oxidation alone). When used in combination, ultrasound followed by enzymatic pretreatment (US+E+AO) yielded the best COD removal efficiencies during aerobic oxidation as compared to the other combinations tested for the treatment of the distillery wastewater. A 4-fold increase in the initial oxidation rate was observed over the untreated batch for the integrated technique (US+E+AO). On the basis of the variation in the values of the biokinetic parameters it can be concluded that the type of pretreatment scheme affects the subsequent rate of the aerobic oxidation significantly.

Ultrasound pre-treatment for enhanced biodegradability of the distillery wastewater.

Studies were carried out to the find out the efficacy of the ultrasonic irradiation as a pre-treatment step for the treatment of one of the polluting industrial effluents, the distillery spentwash. Experiments were carried out on the fresh and stored effluent samples. The effect of the ultrasound exposure on the biodegradability of the effluent was monitored by carrying out its subsequent aerobic oxidation. A comparison has been made between the efficacies of the pre-treated samples with the untreated samples. The results indicate that the ultrasound seems to increase the attractiveness of the conventional aerobic oxidation process by increasing their initial rates of degradation.