Electrospun polydioxanone/fucoidan blend nanofibers loaded with anti-cancer precipitate from Jaspis diastra and paclitaxel: Physico-chemical characterization and in-vitro screening.

Nanofibers for drug delivery systems have gained much attention during the past years. This paper describes for the first time the loading of a bioactive precipitate (JAD) from the marine sponge Jaspis diastra in PDX and fucoidan-PDX. JAD was characterized by LC-MS/MS and the major component was jaspamide (1) with a purity of 62.66 %. The cytotoxicity of JAD was compared with paclitaxel (PTX). JAD and PTX displayed IC50 values of 1.10 ± 0.7 µg/mL and 0.21 ± 0.12 µg/mL on skin fibroblasts L929 cells whilst their IC50 values on uveal MP41 cancer cells, were 2.10 ± 0.55 µg/mL and 1.38 ± 0.68 µg/mL, respectively. JAD was found to be less cytotoxic to healthy fibroblasts compared to PTX. JAD and PTX loaded scaffolds showed sustained release over 96 h in physiological medium which is likely to reduce the secondary cytotoxic effect induced by JAD and PTX alone. The physico-chemical properties of the loaded and unloaded scaffolds together with their degradation and action on tumor microenvironment by using L929 and MP41 cells were investigated. JAD and PTX at a concentration of 0.5 % (drug/polymer, w/w) in the electrospun mats prevented growth and proliferation of L929 and MP41 cells. Co-culture of L929 and MP41 showed that the JAD and PTX loaded mats inhibited the growth of both cells and caused cell death.

Marine sponge-derived/inspired drugs and their applications in drug delivery systems.

Oceans harbor a vast biodiversity that is not represented in terrestrial habitats. Marine sponges have been the richest source of marine natural products reported to date, and sponge-derived natural products have served as inspiration for the development of several drugs in clinical use. However, many promising sponge-derived drug candidates have been stalled in clinical trials due to lack of efficacy, off-target toxicity, metabolic instability or poor pharmacokinetics. One possible solution to this high clinical failure rate is to design drug delivery systems that deliver drugs in a controlled and specific manner. This review critically analyzes drugs/drug candidates inspired by sponge natural products and the potential use of drug delivery systems as a new strategy to enhance the success rate for translation into clinical use.

α-Glucosidase inhibitory activity of marine sponges collected in Mauritius waters.

This report describes the use of α-glucosidase to evaluate the anti-diabetic potential of extracts from marine sponges collected in the Mauritius waters. Initial screening at 1.0 mg/mL of 141 extracts obtained from 47 sponge species revealed 10 extracts with inhibitory activity greater than 85%. Seven of the 10 extracts were further tested at 0.1 and 0.01 mg/mL and only the methanol extract of two sponges namely Acanthostylotella sp. (ASSM) and Echinodictyum pykei (EPM) showed inhibition activity greater than 60% at 0.1 mg/mL with an IC50 value of 0.16 ± 0.02 and 0.04 ± 0.01 mg/mL, respectively, while being inactive at 0.01 mg/mL.

Evaluation of hexane and ethyl acetate extracts of the sponge Jaspis diastra collected from Mauritius Waters on HeLa cells.

OBJECTIVES: Based on previous screening results, the cytotoxic effect of the hexane (JDH) and ethyl acetate extracts (JDE) of the marine sponge Jaspis diastra were evaluated on HeLa cells and the present study aimed at determining their possible mechanism of cell death. METHODS: Nuclear staining, membrane potential change, flow cytometry analysis of cell cycle distribution and annexin V staining were undertaken to investigate the effects of JDE and JDH. Electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance were used to characterize an isolated bioactive molecule. KEY FINDINGS: JDE displayed an IC50 25 times more significant than the JDH. Flow cytometry analysis revealed JDE induced apoptosis in HeLa cells accompanied by the collapse of mitochondrial membrane potential. Fractionation of JDE resulted in the isolation of the known cytotoxic cyclodepsipeptide, Jaspamide. CONCLUSIONS: Taking our results together suggest that JDE can be valuable for the development of anticancer drugs, especially for cervical cancer. Further investigations are currently in progress with the aim to determine and isolate other bioactive compounds from this extract.

Ethyl acetate extract of the Mauritian sponge Jaspis sp. induces cell arrest in human promyelocytic leukemia cells.

Marine sponges are considered as a gold mine of new natural products possessing numerous biological activities. We examined the cytotoxic properties of the ethyl acetate extract (JDE) of the previously unrecorded sponge, Jaspis sp. collected from Mauritius Waters. JDE displayed an interesting IC50 of 0.057±0.04µg/mL on HL-60 cells evaluated by MTS assay. Mitochondrial membrane potential change, microscopic analysis and DNA fragmentation assays also confirmed JDE induced apoptosis on HL-60 cells. Annexin V staining demonstrated that JDE induced apoptosis at different concentrations. Treatment with 100ng/mL of JDE led to an accumulation of cells in G2/M phase after 24 h, causing a significant increase of cells (24h: 5.84%; 48h: 13.41%) in sub-G1 phase suggesting that JDE can induce cell cycle arrest in G2/M phase.

Acetylcholinesterase-inhibitory activities of the extracts from sponges collected in mauritius waters.

Patients diagnosed with Alzheimer's disease (AD) show a characteristic neurochemical deficit of acetylcholine, especially in the basal forebrains. The use of acetylcholinesterase (AChE) inhibitors to retard the hydrolysis of acetylcholine has been suggested as a promising strategy for AD treatment. In this study, we evaluated the acetylcholinesterase inhibitory (AChEI) activities of 134 extracts obtained from 45 species of marine sponges. Thin-layer chromatography (TLC) and microplate assays reveal potent acetylcholinsterase inhibitory activities of two AcOEt extracts from the sponges Pericharax heteroraphis and Amphimedon navalis PULITZER-FINALI. We further investigated the inhibitory kinetics of the extracts and found them to display mixed competitive/noncompetitive inhibition and associated their inhibitory activity partly to terpenoids. Acetylcholinesterase inhibitors from marine organisms have been rarely studied, and this study demonstrated the potential of marine sponges as a source of pharmaceutical leads against neurodegenerative diseases.

Cytotoxic activities of hexane, ethyl acetate and butanol extracts of marine sponges from Mauritian Waters on human cancer cell lines.

The ocean is an exceptional source of natural products with many of them exhibiting novel structural features and bioactivity. As one of the most interesting phylum with respect to pharmacological active marine compounds, Poriferas have been investigated widely in the last few decades. A total of 60 organic extracts (hexane, ethyl acetate and butanol) from 20 species of marine sponges from Mauritius were screened at 50µg/ml in an in vitro screening assay against 9 human cancer cell lines. From these tested extracts, many exhibited pronounced cytotoxic effect at least in one of the cell lines and cell type cytotoxic specificity was observed. 27% of ethyl acetate, 11% of hexane and 2% of butanol extracts were found to possess a cytotoxicity ≥75% on 9 different cancer cell lines with the sponges Petrosia sp. 1, Petrosia sp. 2, Pericharax heteroraphis and Jaspis sp. being the most active. Overall, the HL-60cells were much more sensitive to most of the extracts than the other cell lines. We further evaluated the properties of the ethyl acetate (JDE) and hexane extract (JDH) of one sponge, Jaspis sp. on KB cells. JDE displayed a smaller IC(50) than JDH. Clonogenic assay confirmed the antiproliferative effect of both extracts while mitochondrial membrane potential change and microscopic analysis demonstrated extracts-induced apoptosis. Treatment with 100ng/ml of JDE led to a significant increase of cells (24h: 4.02%; 48h: 26.23%) in sub-G1 phase. The cytotoxic properties of the tested extracts from these sponges suggest the presence of compounds with pharmacological potential and are currently undergoing fractionation to isolate the active constituents.