Cytotoxic compounds from a marine actinomycete, Streptomyces albovinaceus var. baredar AUBN10/2

Marine sediment samples from Machilipatnam (Krishna District, A.P) coast off Bay of Bengal, India wereinvestigated as a source of actinomycetes to screen for the production of novel bioactive compounds. More than 10,000 bioactive compounds have been described from marine actinomycetes, with many different properties, ranging from colour pigments to cytotoxic compounds. The search for cytotoxic compounds is continuing due to the demand for new anticancer drugs. In this work, compound I was isolated from the marine derived actinomycete strain AUBN10/2, obtained from marine sediment samples of Bay of Bengal, India. This was obtained by solvent extraction followed by chromatographic purification. The pure compound I was identified from spectroscopic data which was related to the actinomycin D, it showed a potent cytotoxic activity against cell lines HMO2 (gastric adenocarcinoma) and HePG2 (hepatic carcinoma) in vitro. It also exhibited antimicrobial activities against gram positive and negative bacteria.Key words: Marine actinomycetes, phenoxazinone chromophore, actinomycin D, cytotoxic compounds,antibacterial activity

Dissolution behaviour of aceclofenac-PVP coprecipitates

Aim: The objective of the present investigation was to study the effect of PVP on in vitro dissolution of aceclofenac from coprecipitates. Materials and Methods: Aceclofenac coprecipitates (CP) with different drug loadings were prepared and in vitro dissolution studies of pure drug, physical mixtures and coprecipitates were carried out. Results: Coprecipitates of aceclofenac with PVP showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1 N HCl, pH1.2 and phosphate buffer, pH, 7.4. Coprecipitates in 1:2 ratio showed maximum dissolution rate in comparison to other ratios. Amorphous nature of the drug in coprecipitates was confirmed by scanning electron microscopy and a decrease in enthalpy of drug melting in coprecipitates compared to the pure drug. FT- IR spectroscopy and differential scanning calorimetry studies indicated no interaction between aceclofenac and PVP in coprecipitates in solid state. Dissolution enhancement was attributed to decreased crystallinity of the drug and to the wetting, eutectic formation and solubilizing effect of the carrier from the coprecipitates of aceclofenac. Conclusion: dissolution of aceclofenac can be enhanced by the use of hydrophilic carriers like PVP

PREPERATION AND IN VITRO EVALUATION OF SOLID DISPERSIONS OF NIMODIPINE USING PEG 4000 AND PVP K3

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug, nimodipine, by a solid dispersion technique. Solid dispersions were prepared by using polyethylene glycol 4000 (PEG- 4000) and polyvinylpyrrolidone K30 (PVPK30) in different drug-to-carrier ratios. The solid dispersions were prepared by melting method. Morphology of solid dispersions was characterised by scanning electron microscope. The pure drug, physical mixtures and solid dispersions were characterized by in vitro dissolution study. Dissolution characteristics were determined by using pH 4.5 acetate buffer containing 0.3% SDS. The very slow dissolution rate was observed for pure nimodipine and the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. Solid dispersions prepared with PEG-4000 and PVPK30 showed the highest improvement in wettability and dissolution rate of nimodipine. Even physical mixtures of nimodipine prepared with both polymers also showed better dissolution profile than that of pure nimodipine. In conclusion, dissolution of nimodipine can be enhanced by the use of hydrophilic carriers PEG-4000 and PVPK30

Preparation and in vitro characterization of non-effervescent floating drug delivery system of poorly soluble drug, carvedilol phosphate

The objective of the study was to enhance the solubility of carvedilol phosphate and to formulate it into non-effervescent floating tablets using swellable polymers. Solid dispersions (SD)of carvedilol were prepared with hydrophilic carriers such as polyvinylpyrrolidone and poloxamer to enhance solubility. Non-effervescent floating tablets were prepared with a combination of optimized solid dispersions and release retarding polymers/swellable polymers such as xanthan gum and polyethylene oxide. Tablets were evaluated for physicochemical properties such as hardness, thickness and buoyancy. SD prepared with the drug to poloxamer ratio of 1:4 by melt granulation showed higher dissolution rate than all other dispersions. Formulations containing 40 mg of polyethylene oxide (C-P40) and 50 mg xanthan gum (C-X50) were found to be best, with the drug retardation up to 12 hours. Optimized formulations were characterized using FTIR and DSC and no drug and excipient interactions were detected

Kristalne modifikacije i profil oslobađanja piroksikama

Piroxicam is a nonsteroidal anti-inflammatory drug with low aqueous solubility which exhibits polymorphism. The present study was carried out to develop polymorphs of piroxicam with enhanced solubility and dissolution rate by the crystal modification technique using different solvent mixtures prepared with PEG 4000 and PVP K30. Physicochemical characteristics of the modified crystal forms of piroxicam were investigated by X-ray powder diffractometry, FT-IR spectrophotometry and differential scanning calorimetry. Dissolution and solubility profiles of each modified crystal form were studied and compared with pure piroxicam. Solvent evaporation method (method I) produced bothneedle and cubic shaped crystals. Slow crystallization from ethanol with addition of PEG 4000 or PVP K30 at room temperature (method II) produced cubic crystal forms. Needle forms produced by method I improved dissolution but not solubility. Cubic crystals produced by method I had a dissolution profile similar to that of untreated piroxicam but showed better solubility than untreated piroxicam. Cubic shaped crystals produced by method II showed improved dissolution, without a significant change in solubility. Based on the XRPD results, modified piroxicam crystals obtained by method I from acetone/benzene were cube shaped, which correlates well with the FTIR spectrum; modified needle forms obtained from ethanol/methanol and ethanol/acetone showed a slight shift of FTIR peak that may be attributed to differences in the internal structure or conformation.Piroksikam je nesteroidni protuupalni lijek male topljivosti u vodi koji ima svojstvo polimorfije. Cilj rada bio je priprema polimorfa piroksikama povećane topljivosti i brzine oslobađanja koristeći smjese različitih otapala i PEG 4000, odnosno PVP K30. Fizikokemijska svojstva modificiranih kristalnih oblika piroksikama ispitivana su difrakcijom X-zraka na praškastom uzorku FT-IR spektrofotometrijom i diferencijalnom pretražnom kalorimetrijom. Profili oslobađanja i topljivosti modificiranih kristalnih oblika proučavani su i uspoređivani sa čistim piroksikamom. Metodom uparavanja otapala (metoda I) dobiveni su igličasti i kubični kristali. Polaganom kristalizacijom iz etanola uz dodatak PEG 4000 ili PVP K30 na sobnoj temperaturi (metoda II) dobiveni su kubični kristali. Igličasti kristali dobiveni metodom I poboljšali su oslobađanje, ali ne i topljivost. Kubični kristali dobiveni metodom I imali su poboljšanu topljivost, ali sličan profil oslobađanja kao i netretirani piroksikam. Kubični kristali dobiveni metodom II imali su poboljšani profil oslobađanja, bez značajne promjene u topljivosti. Na temelju XRPD rezultata, modificirani kristali piroksikama dobiveni metodom I iz smjese acetona i benzena bili su kubični, što dobro korelira s FTIR spektrom; modificirani igličasti kristali dobiveni iz smjese etanol/metanol i etanol/aceton imali su lagani pomak FTIR signala što bi se moglo pripisati razlikama u internoj strukturi ili konformacijama

Central Composite Designed Formulation, Characterization and In-Vitro Cytotoxic effect of Erlotinib Loaded Chitosan Nanoparticulate System

© 2019 Elsevier B.V. The most common cause of deaths due to cancers nowadays is lung cancer. The objective of this study was to prepare erlotinib loaded chitosan nanoparticles for their anticancer potential. To study the effect of formulation variables on prepared nanoparticles using central composite design. Erlotinib loaded chitosan nanoparticles were prepared by ionic gelation method using probe sonication technique. It was found that batch NP-7 has a maximum loading capacity and entrapment efficiency with a particle size (138.5 nm) which is ideal for targeting solid tumors. Analysis of variance was applied to the particle size, entrapment efficiency and percent cumulative drug release to study the fitting and the significance of the model. The batch NP-7 showed 91.57% and 39.78% drug release after 24 h in 0.1 N hydrochloric acid and Phosphate Buffer (PB) pH 6.8, respectively. The IC50 value of NP-7 evaluated on A549 Lung cancer cells was found to be 6.36 μM. The XRD of NP-7 displayed the existence of erlotinib in the amorphous pattern. The optimized batch released erlotinib slowly in comparison to the marketed tablet formulation. Erlotinib loaded chitosan nanoparticles were prepared successfully using sonication technique with suitable particle size, entrapment efficiency and drug release. The formulated nanoparticles can be utilized for the treatment of lung cancer

Marine Antitumor Drugs: Status, Shortfalls and Strategies

Cancer is considered as one of the deadliest diseases in the medical field. Apart from the preventive therapies, it is important to find a curative measure which holds no loopholes and acts accurately and precisely to curb cancer. Over the past few decades, there have been advances in this field and there are many antitumor compounds available on the market, which are of natural as well as synthetic origin. Marine chemotherapy is well recognized nowadays and profound development has been achieved by researchers to deal with different molecular pathways of tumors. However, the marine environment has been less explored for the production of safe and novel antitumor compounds. The reason is a number of shortfalls in this field. Though ample reviews cover the importance and applications of various anticancerous compounds from marine natural products, in the present review, we have tried to bring the current status of antitumor research based on marine inhibitors of cancer signaling pathways. In addition, focus has been placed on the shortfalls and probable strategies in the arena of marine antitumor drug discovery

A Tropical Marine Microbial Natural Products Geobibliography as an Example of Desktop Exploration of Current Research Using Web Visualisation Tools

Microbial marine biodiscovery is a recent scientific endeavour developing at a time when information and other technologies are also undergoing great technical strides. Global visualisation of datasets is now becoming available to the world through powerful and readily available software such as Worldwind™, ArcGIS Explorer™ and Google Earth™. Overlaying custom information upon these tools is within the hands of every scientist and more and more scientific organisations are making data available that can also be integrated into these global visualisation tools. The integrated global view that these tools enable provides a powerful desktop exploration tool. Here we demonstrate the value of this approach to marine microbial biodiscovery by developing a geobibliography that incorporates citations on tropical and near-tropical marine microbial natural products research with Google Earth™ and additional ancillary global data sets. The tools and software used are all readily available and the reader is able to use and install the material described in this article

Immense Essence of Excellence: Marine Microbial Bioactive Compounds

Oceans have borne most of the biological activities on our planet. A number of biologically active compounds with varying degrees of action, such as anti-tumor, anti-cancer, anti-microtubule, anti-proliferative, cytotoxic, photo protective, as well as antibiotic and antifouling properties, have been isolated to date from marine sources. The marine environment also represents a largely unexplored source for isolation of new microbes (bacteria, fungi, actinomycetes, microalgae-cyanobacteria and diatoms) that are potent producers of bioactive secondary metabolites. Extensive research has been done to unveil the bioactive potential of marine microbes (free living and symbiotic) and the results are amazingly diverse and productive. Some of these bioactive secondary metabolites of microbial origin with strong antibacterial and antifungal activities are being intensely used as antibiotics and may be effective against infectious diseases such as HIV, conditions of multiple bacterial infections (penicillin, cephalosporines, streptomycin, and vancomycin) or neuropsychiatric sequelae. Research is also being conducted on the general aspects of biophysical and biochemical properties, chemical structures and biotechnological applications of the bioactive substances derived from marine microorganisms, and their potential use as cosmeceuticals and nutraceuticals. This review is an attempt to consolidate the latest studies and critical research in this field, and to showcase the immense competence of marine microbial flora as bioactive metabolite producers. In addition, the present review addresses some effective and novel approaches of procuring marine microbial compounds utilizing the latest screening strategies of drug discovery