PEG-PLA nanoparticles decorated with small-molecule PSMA ligand for targeted delivery of galbanic acid and docetaxel to prostate cancer cells.

Prostate cancer (PCa) is one of the most prevalent non-drug delivery system cutaneous malignancies. Undoubtedly, introducing novel treatment options to achieve higher therapeutic index will be worthwhile. In this study, we report for the first time, a novel targeted self-assembled based on PEG-PLA nanoparticles (PEG-PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ((S)-2-(3-((S)-5-amino-1-carboxypentyl) ureido) pentanedioic acid (ACUPA), a small molecule inhibitor targeting prostate-specific membrane antigen (PSMA), in prostate cancer cell line. The prepared NPs were characterized by different analytical methods. The MTT assay was used to compare the anti-proliferation of drugs-loaded PEG-PLA NPs and ACUPA-PEG-PLA against LNCaP (PSMA+ ) and PC3 (PSMA- ) cells. PEG-PLA NPs with an average size of 130-140 nm had an enhanced release of GBA and docetaxel at pH 5.5 compared with pH 7.5. Spectrofluorometric analysis suggested that ACUPA-modified PEG-PLA could effectively enhance the drug uptake in PSMA+ prostate cancer cells. Cytotoxicity studies showed that the targeted NPs loaded with different concentrations of GBA and fixed concentration of docetaxel (4 nM) have shown higher toxicity (IC50 30 ± 3 µM) than both free GBA (80 ± 4.5 µM) and nontargeted NPs (IC50 40 ± 4.6 µM) in LNCaP cells. Collectively, these findings suggest that ACUPA-conjugated PEG-PLA nanosystem containing GBA and docetaxel is a viable delivery carrier for various cancer-targeting PSMA that suffer from short circulation half-life and limited therapeutic efficacy.

Formulation and evaluation of anticancer and antiangiogenesis efficiency of PLA-PEG nanoparticles loaded with galbanic acid in C26 colon carcinoma, in vitro and in vivo.

Galbanic acid (GBA) is an active sesquiterpene coumarin derivative, with various medicinal benefits, including anticancer properties. However, the low solubility of GBA is the main limitation of its clinical applications. In this study, we used a nanosystem based on poly (D, l-lactide)-polyethylene glycol (PLA-PEG), for the delivery of GBA to C26 colon carcinoma cells. The physicochemical characteristics of nanoparticles (NPs) prepared by the emulsification-evaporation method were evaluated. MTT assay was used to compare the anticell proliferation of GBA and PLA-PEG-GBA against C26 cell lines. PLA-PEG-NPs with an average size of about 140 nm had an enhanced release of GBA at a pH of 5.5 compared with a pH of 7.4. Cytotoxicity studies showed that the IC 50 of the PLA-PEG-GBA NPs (8 µM) was significantly lower than free GBA (15 µM). In the in vivo study, PLA-PEG-GBA NPs exhibited remarkable efficacy and reduced in vivo toxicity in C26 colon carcinoma tumor-bearing female BALB/c mice. To study the antiangiogenesis effect of the NPs, tumor sections were stained with an anti CD34 antibody. The results show the CD34 (+) vessels were decreased in the GBA and PLA-PEG-GBA treated mice by more than 75% and 90%, respectively. These results suggest that the encapsulation of GBA into the PLA-PEG could potentially be used for the treatment of colorectal cancer.

Ionic-liquid-based hollow-fiber liquid-phase microextraction method combined with hybrid artificial neural network-genetic algorithm for speciation and optimized determination of ferro and ferric in environmental water samples.

A novel and environmentally friendly ionic-liquid-based hollow-fiber liquid-phase microextraction method combined with a hybrid artificial neural network (ANN)-genetic algorithm (GA) strategy was developed for ferro and ferric ions speciation as model analytes. Different parameters such as type and volume of extraction solvent, amounts of chelating agent, volume and pH of sample, ionic strength, stirring rate, and extraction time were investigated. Much more effective parameters were firstly examined based on one-variable-at-a-time design, and obtained results were used to construct an independent model for each parameter. The models were then applied to achieve the best and minimum numbers of candidate points as inputs for the ANN process. The maximum extraction efficiencies were achieved after 9 min using 22.0 µL of 1-hexyl-3-methylimidazolium hexafluorophosphate ([C6MIM][PF6]) as the acceptor phase and 10 mL of sample at pH = 7.0 containing 64.0 µg L(-1) of benzohydroxamic acid (BHA) as the complexing agent, after the GA process. Once optimized, analytical performance of the method was studied in terms of linearity (1.3-316 µg L(-1), R (2) = 0.999), accuracy (recovery = 90.1-92.3%), and precision (relative standard deviation (RSD) <3.1). Finally, the method was successfully applied to speciate the iron species in the environmental and wastewater samples.

Recent advances in co-delivery systems based on polymeric nanoparticle for cancer treatment.

Cancer is a broad term for a class of prevalent diseases as one in three people develop cancer during their lifetime. Although, there are few success stories of cancer therapy, most of the existing medications do not lead to complete recovery. Because of the complexity of cancer, usually a single therapeutic approach is insufficient for the suppression of cancer growth and metastasis. Simultaneous loading and co-delivery of different agents with different physiochemical characteristics to the same tumors have been suggested for minimizing the dose of anticancer drugs and achieving the synergistic therapeutic impacts in cancers treatment. Intense work to develop nanotechnology-based systems as a suitable option for cancer treatment is currently underway. The purpose of this review is to provide an overview of the co-delivery systems based on polymeric nanoparticles including polymeric micelles, dendrimers, poly-d,l-lactide-co-glycolide, polyethylenimine, poly(l-lysine) and chitosan for efficacious cancer therapy.

In-syringe reversed dispersive liquid-liquid microextraction for the evaluation of three important bioactive compounds of basil, tarragon and fennel in human plasma and urine samples.

In the present study, an efficient and environmental friendly method (called in-syringe reversed dispersive liquid-liquid microextraction (IS-R-DLLME)) was developed to extract three important components (i.e. para-anisaldehyde, trans-anethole and its isomer estragole) simultaneously in different plant extracts (basil, fennel and tarragon), human plasma and urine samples prior their determination using high-performance liquid chromatography. The importance of choosing these plant extracts as samples is emanating from the dual roles of their bioactive compounds (trans-anethole and estragole), which can alter positively or negatively different cellular processes, and necessity to a simple and efficient method for extraction and sensitive determination of these compounds in the mentioned samples. Under the optimum conditions (including extraction solvent: 120 µL of n-octanol; dispersive solvent: 600 µL of acetone; collecting solvent: 1000 µL of acetone, sample pH 3; with no salt), limits of detection (LODs), linear dynamic ranges (LDRs) and recoveries (R) were 79-81 ng mL(-1), 0.26-6.9 µg mL(-1) and 94.1-99.9%, respectively. The obtained results showed that the IS-R-DLLME was a simple, fast and sensitive method with low level consumption of extraction solvent which provides high recovery under the optimum conditions. The present method was applied to investigate the absorption amounts of the mentioned analytes through the determination of the analytes before (in the plant extracts) and after (in the human plasma and urine samples) the consumption which can determine the toxicity levels of the analytes (on the basis of their dosages) in the extracts.

In-vitro Antimicrobial Activities of Some Iranian Conifers.

Male and female leaves and fruits of eleven different taxons of Iranian conifers (Cupressus sempervirens var. horizontalis, C. sempervirens var. sempervirens, C. sempervirens cv. Cereifeormis, Juniperus communis subsp. hemisphaerica, J. excelsa subsp. excelsa, J. excelsa subsp. polycarpos, J. foetidissima, J. oblonga, J. sabina, Platycladus orientalis and Taxus baccata) were collected from different localities of Iran, dried and extracted with methanol. The extracts were tested for their antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Candida albicans. The extracts were screened qualitatively using four different methods, the disc diffusion, hole plate, cylinder agar diffusion and agar dilution methods, whereas the minimum inhibitory concentrations (MIC) of each extract were determined by the agar dilution method. The best result was obtained by means of hole plate method in qualitative determination of antimicrobial activities of extracts and the greatest activity was found against S. aureus in all tested methods.

Protective Effect of Scutellaria litwinowii Extract on Serum/Glucose-Deprived Cultured PC12 Cells and Determining the Role of Reactive Oxygen Species.

Considering the wide, positive reporting of the role of reactive oxygen species in ischemic brain injury, searching for antioxidant drugs within herbal remedies is logical. In this study, the protective effects of Scutellaria litwinowii Bornm. & Sint. on cell viability and reactive oxygen species production in cultured PC12 cells were investigated under serum/glucose-deprivation-induced cell death. After cells were seeded overnight, they were then deprived of serum/glucose for 24 h. Cells were treated with different concentrations of S. litwinowii extract (7.75-250 µg/mL). Cell viability was quantitated by MTT assay, and intracellular reactive oxygen species production was measured by flow cytometry. Serum/glucose-deprivation induced significant cell death after 24 h (P < 0.001). Treatment with S. litwinowii (7.75-250 µg/mL) reduced serum/glucose deprivation-induced cytotoxicity in PC12 cells after 24 h. A significant increase in intracellular reactive oxygen species production was seen following serum/glucose deprivation (P < 0.001). S. litwinowii (62 and 125 µg/mL, P < 0.01) treatment reversed the increased reactive oxygen species production following ischemic insult. This demonstrates that S. litwinowii extract protects PC12 cells against serum/glucose-deprivation-induced cell death by antioxidant mechanisms, which indicates the potential therapeutic application of S. litwinowii in managing cerebral ischemic and neurodegenerative disorders.