Sodium alginate-guar gum and carbopol based methotrexate loaded mucoadhesive microparticles for colon delivery: An in vitro evaluation

Methotrexate (MTX) is famous for its therapeutic potential against different cancers including colorectal cancer. Goal of the present investigation was to formulate MTX loaded mucoadhesive microparticles for colon targeting. The optimized formulation (MTX-MS2) was composed of mucoadhesive polymers (sodium alginate, guar gum and carbopol 940) in an appropriate ratio. MTXMS2 was developed by ionic-gelation method. The suitable particle size and zeta potential were found to be 21.10 ± 0.18 µm and 3.01 ± 0.16 mV for MTX-MS2 respectively. The % yield (98.60 ± 2.12), % entrapment efficiency (97.98 ± 1.22) and % drug loading (1.04 ± 0.03) were estimated for MTXMS2. The swelling index (0.99 ± 0.04 θ) and mucoadhesion (97.29 ± 4.61%) were significantly (***P ˂ 0.01) achieved with MTX-MS2 as compared to other formulations. The optimum drug release (96.07 ± 4.52%) was significantly achieved with MTX-MS2 at simulated gastric fluid (pH 7.4) for 36 h in a sustained manner. This profile may be attributed towards excellent mucoadhesivness of the polymers used in the formulation. Therefore, the current investigation suggests that mucoadhesive carrier system could be promising approach for colon delivery. Thus, the proposed work would be helpful for the treatment of colorectal canc

Bioinspired Polymeric-based Core-shell Smart Nano-systems.

Smart nanosystems (SNs) have the potential to revolutionize drug delivery. Conventional drug delivery systems have poor drug-loading, early burst release, limited therapeutic effects, etc. Thus, to overcome these problems, researchers have taken advantage of the host-guest interactions as bioinspired nanosystems which can deliver nanocarriers more efficiently with the maximum drug loading capacity and improved therapeutic efficacy as well as bioavailability. SNs employ nanomaterials to form cage molecules by entrapping new nanocarriers called smart nanosystems in their cargo and design. The activities of SNs are based on responsive materials that interact with the stimuli either by changing their properties or conformational structures. The aptitude of living systems to respond to stimuli and process information has encouraged researchers to build up integrated nanosystems exhibiting similar function and therapeutic response. Various smart materials, including polymers, have been exhaustively employed in fabricating different stimuli-responsive nanosystems which can deliver bioactive molecules to a specific site for a certain period with minimal side effects. SNs have been widely explored to deliver diverse kinds of therapeutic agents ranging from bioactive compounds, genes, and biopharmaceuticals like proteins and peptides, to diagnostic imaging agents for biomedical applications. Nanotechnology-based different nanosystems are promising for health care issues. The advancement of SNs with physical science and engineering technology in synthesizing nanostructures and their physicochemical characterization should be exploited in medicine and healthcare for reducing mortality rate, morbidity, disease prevalence and general societal burden.

Development and in vitro/in vivo evaluation of artemether and lumefantrine co-loaded nanoliposomes for parenteral delivery.

Combination therapy of artemether (ART) and lumefantrine (LUM) is well-established for the treatment of uncomplicated malaria worldwide. Nanoliposomes (NLs) encapsulating both drugs were prepared and freeze-dried. The lyophilized nanoliposomes exhibited high entrapment efficiency of artemether (66.18%), relatively low entrapment efficiency of lumefantrine (53.46%), low average size diameter (125.3 nm) and found to be stable at 4 °C for 60 days without significant change in mean particle diameter and drug entrapment efficiencies. In vitro drug release study has shown initial burst effect and then sustained release pattern over a time period of 30 h. In vivo toxicity study was examined by liver and kidney function test as well as histopathological examination. Nanoliposomes showed lower hemolytic potential (∼10%) compared to all the components when studied individually. There was no significant change (p > 0.05) in biochemical parametes between control and treated group of animals. Pharmacokinetic data of ART + LUM NLs showed higher the area under the plasma concentration-time curve (AUC) values and prolonged residence time of drug in the blood circulation compared with ART + LUM solution. The tissue distribution demonstrated high uptake of ART + LUM-NLs in RES organs particularly in liver and spleen. Biocompatibility was confirmed by hepato- and nephrotoxicity analysis showed no sign of fibrosis, fatty infiltration, centrilobular necrosis and lymphocyte infiltration confirmed the suitability of developed formulation for treatment of malaria.

Solvent Extraction and Gas Chromatography-Mass Spectrometry Analysis of Annona squamosa L. Seeds for Determination of Bioactives, Fatty Acid/Fatty Oil Composition, and Antioxidant Activity.

The yield and fatty oil components of the seed kernels of Annona squamosa L. (Family: Annonaceae) were determined by solvent extraction method and gas chromatography-mass spectrometry (GC-MS). Seeds were extracted with ethanol and further fractionated with n-hexane. The free radical-scavenging activities of both ethanolic and n-hexane fraction against 1, 1-diphenyl-2-picrylhydrazyl (DPPH) were determined by UV spectrophotometer at 517 nm. Phytochemical screening revealed the presence of numerous bioactive compounds including steroids, flavonoids, terpenoids, fatty acids, and different types of ester compounds. The prevailing compounds found in ethanolic fraction were n-hexadecanoic acid (10.08%), heptadecene-(8)-carbonic acid-(1) (29.68%), octadecanoic acid (3.61%), 9-octadecenoic acid (Z)-2,3-dihydroxypropyl ester (5.14%), ergost-5-en-3-ol (3.68%), stigmasta-5,22-dien-3-ol (5.93%), and y-sitosterol (8.25%). Compounds found in n-hexane fraction were mainly n-hexadecanoic acid (14.42%), 9,12-octadecadienoic acid (2.87%), cis-vaccenic acid (10.39%), 9-octadecenoic acid (7.03%), hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester (4%), 9-octadecenoic acid (Z)-, 2,3-dihydroxypropyl ester (13.33%), ergost-5-en-3-ol (4.04%), stigmasta-5,22-dien-3-ol, (3.beta.,22e) (6.07%), and y-sitosterol (10.87%). The crude fatty oil was converted into methyl esters and analyzed by GC-MS. Eleven compounds constituting 99.9% of the oil were identified. The presence of saturated and unsaturated fatty acids in ethanolic and n-hexane fraction of A. squamosa seed extract justify the use of this plant to treat many ailments in folk and herbal medicine. Both the fractions have shown significant antioxidant activity. The presence of phenolic compounds and unsaturated fatty acids are reported as possible contributors for antioxidant activity of seed extract.

The Role of Tamarix gallica Leaves Extract in Liver Injury Induced by Rifampicin Plus Isoniazid in Sprague Dawley Rats.

The Tamarix gallica leaves extract (TGLE) was investigated for hepatoprotective potential against rifampicin (RIF) plus isoniazid (INH)-induced liver injury in Sprague Dawley (SD) rats. All the rats of groups III and IV received 100 and 200 mg/kg body wt, respectively, of the suspension of TGLE while group V received silymarin 100 mg/kg body wt orally. After 10 min, they, along with group II, received INH plus RIF each day (50 mg/kg body wt, by mouth (PO) each) for 28 days. Group I received 10 ml/kg body wt, PO of vehicle, i.e., 1% aqueous carboxymethyl cellulose (1% CMC) throughout the study. At the end of the experiment, blood was obtained through the retro-orbital plexus under light anesthesia and the serum was separated from the sacrificed animals. A small portion of isolated liver tissue was fixed in 10% formaldehyde for histopathological examinations. The levels of elevated serum bilirubin (p > .05-p < .05), alanine transaminase (p > .05-p < .01), aspartate transaminase (p > .05-p < .01), alkaline phosphatase (p < .05-p < .01), lactate dehydrogenase (p < .05-p < .01), and cholesterol (p > .05-p < .01) decreased while the levels of decreased total protein (p > .05-p < .05) and albumin (p < .05-p < .05) increased in TGLE-treated groups III and IV as compared to group II, and the serum marker enzyme levels were toward normal, indicating protection against liver injury. It was well supported with histopathological results. Thus, Tamarix gallica leaves extract possesses promising hepatoprotective activity against RIF plus INH-induced liver injury in experimental rats.

Role of excipients in successful development of self-emulsifying/microemulsifying drug delivery system (SEDDS/SMEDDS).

The oral delivery of hydrophobic drug presents a major challenge because of the low aqueous solubility of such compounds. Self-emulsifying/microemulsifying drug delivery system (SEDDS/SMEDDS), which are isotropic mixtures of oils, surfactants, solvents and co-solvents/surfactants, can be used for the design of formulations in order to improve the oral absorption of highly lipophilic drug compounds. The efficiency of oral absorption of said drug from such type of formulation depends on many formulation-related parameters, such as surfactant concentration, oil/surfactant ratio, polarity of the emulsion, droplet size and charge, all of which in essence determine the self-emulsification ability. Thus, only very specific pharmaceutical excipient combinations will lead to efficient self-emulsifying systems. With the growing interest in this field, there is an increasing need for guidelines in excipient selection to obtain effective delivery system with improved bioavailability. The aim of this review is to present the recent approaches in selecting the most appropriate lipid system(s); methods for its characterization and role of various excipients for improved delivery of dosage form.

HybridSPE: A novel technique to reduce phospholipid-based matrix effect in LC-ESI-MS Bioanalysis.

When complex biological materials are analyzed without an adequate sample preparation technique, MS signal and response undergo significant alteration and result in poor quantification and assay. This problem generally takes place due to the presence of several endogenous materials component in samples. One of the major causes of ion suppression in bioanalysis is the presence of phospholipids during LC-MS analysis. The phospholipid-based matrix effect was investigated with a commercially available electro spray ionization (ESI) source coupled with a triple quadrupole mass spectrometer. HybridSPE dramatically reduced the levels of residual phospholipids in biological samples, leading to significant reduction in matrix effects. This new procedure that combines the simplicity of precipitation with the selectivity of SPE allows obtaining much cleaner extracts than with conventional procedures. HybridSPE-precipitation procedure provides significant improvement in bioanalysis and a practical and fast way to ensure the avoidance of phospholipids-based matrix effects. The present review outlines the HybridSPE technique to minimize phospholipids-based matrix effects on LC-ESI-MS bioanalysis.

Formulation, antimicrobial and toxicity evaluation of bioceramic based ofloxacin loaded biodegradable microspheres for periodontal infection.

In the present study an attempt has been made to load Poly (Lactic-Co-glycolic acid) microspheres with hydroxyapatite (HA) and ofloxacin and propose the composite microspheres to be used as local drug delivery system with the drug releasing capability for periodontitis treatment. A modified single emulsion method has been used for the preparation of microspheres. Experiments were conducted to optimize the formulation by RSM-Box-Behnken Method, which is an independent quadratic design involving three or four independent variables against a pre determined set of dependant parameters. The particle size of composite microspheres was analyzed and the average size was found to be 22.05 µm. Photomicrographs and scanning electron micrographs showed that the composite microspheres are spherical in shape and porous in nature. The microbiological activity of optimized formulation was evaluated using strain: S. aureus-ATCC- 29213 and E. coli-ATCC-25922. In vivo/in situ toxicity evaluation of the formulation was assessed by MTT assay and the formulation was found to be biocompatible.

Current approaches toward production of secondary plant metabolites.

Plants are the tremendous source for the discovery of new products with medicinal importance in drug development. Today several distinct chemicals derived from plants are important drugs, which are currently used in one or more countries in the world. Secondary metabolites are economically important as drugs, flavor and fragrances, dye and pigments, pesticides, and food additives. Many of the drugs sold today are simple synthetic modifications or copies of the naturally obtained substances. The evolving commercial importance of secondary metabolites has in recent years resulted in a great interest in secondary metabolism, particularly in the possibility of altering the production of bioactive plant metabolites by means of tissue culture technology. Plant cell and tissue culture technologies can be established routinely under sterile conditions from explants, such as plant leaves, stems, roots, and meristems for both the ways for multiplication and extraction of secondary metabolites. In vitro production of secondary metabolite in plant cell suspension cultures has been reported from various medicinal plants, and bioreactors are the key step for their commercial production. Based on this lime light, the present review is aimed to cover phytotherapeutic application and recent advancement for the production of some important plant pharmaceuticals.

Estimation of sertraline by chromatographic (HPLC-UV273 nm) technique under hydrolytic stress conditions.

PURPOSE: In this paper, simple, specific and accurate RP-HPLC method was developed in order to study decomposition of sertraline (SRT) under the hydrolytic stress conditions (acid, neutral, alkaline and oxidative). MATERIALS AND METHODS: The best separation of SRT and its degradation products were achieved on reverse phase LiChoCART with Purospher (RP-18e) column. The mobile phase was composed of methanol/water (75:25, v/v). The detection wavelength was 273 nm. The method was validated and response was found to be linear in the drug concentration range of 10-200 µg ml-1 with correlation coefficient of 0.998. RESULTS: The RSD values for intra- and inter-day precision were < 0.65 and < 0.72%, respectively. Employing RP-HPLC method, degradation products were detected in the exposed samples. CONCLUSION: IT WAS FOUND THAT THE SUSCEPTIBILITY OF SRT TO HYDROLYTIC DECOMPOSITION INCREASED IN FOLLOWING MANNER: Neutral condition < alkaline condition < acid condition < oxidative condition.

Oral lipid based drug delivery system (LBDDS): formulation, characterization and application: a review.

The major problem in oral drug formulations is low and erratic bioavailability, which mainly results from poor aqueous solubility. This may lead to high inter- and intra subject variability, lack of dose proportionality and therapeutic failure. The improvement of bio-availability of drugs with such properties presents one of the greatest challenges in drug formulations. Oral lipid based formulations are attracting considerable attention due to their capacity to increase the solubility, facilitating gastrointestinal absorption and reduce or eliminate the effect of food on the absorption of poorly water soluble, lipophilic drug and thus increasing the bioavailability. The present review outlines the recent findings on self-emulsifying drug delivery system (SEDDS), self-micro/nanoemulsifying drug delivery system (SMEDDS/SNEDDS) and evaluation of these formulations published over the past decade. The application of lipid based formulations as a promising system for the oral delivery of many therapeutic agents including traditional medicine (TM) has also been examined in the current review.

Role of humic acid on oral drug delivery of an antiepileptic drug.

CONTEXT: Humic acid (HA) is omnipresent in natural organic matter that is a macromolecular, negatively charged polyelectrolyte that contains a hydrophobic core. It is also present in a significant amount in Shilajit (used frequently in traditional medicines), which is used in this study as a source of extraction. HA is evaluated for the oral drug delivery of carbamazepine (CBZ). OBJECTIVE: HA is used in this study to increase the dissolution, intestinal permeation, and pharmacodynamic response of CBZ (bio pharmaceutics classification system (BCS) II) by the technique of complexation and other related mechanism reported with humic substances. METHODS: Different complexation techniques were explored in this study for the entrapment of CBZ, which was authenticated by molecular modeling and conformational analysis. These were further characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). Solubility analysis and dissolution release profile were carried out to access the in vitro parameters. For ex vivo studies, rat gut intestinal permeability was done. And finally pharmacodynamic evaluation (maximal electroshock method) was carried out for optimized complexes. RESULTS: Molecular modeling approach and instrumental analysis (DSC, XRD, and FT-IR) confirmed the entrapment of CBZ inside the complexing agent. Increased solubility (∼1742%), sustained release (∼78%), better permeability (∼3.5 times), and enhanced pharmacodynamic responses conferred the best to 1:2 freeze dried (FD) and then 1:2 kneading (KD) complexes compared with pure CBZ. CONCLUSION: Now it could be concluded that HA may be tried as a complexing agent for antiepileptic drug and other classes of low water-soluble drug.