Search results for: Colon targeted drug delivery.

Authors: Anil Bhandari, Imran Khan Pathan, Peeyush K. Sharma, Rakesh K. Patel, Suresh Purohit

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The purpose of this study was to prepare time and pH dependent release tablets of Ayurvedic Churna formulation and evaluate their advantages as colon targeted drug delivery system. The Vidangadi Churna was selected for this study which contains Embelin and Gallic acid. Embelin is used in Helminthiasis as therapeutic agent. Embelin is insoluble in water and unstable in gastric environment so it was formulated in time and pH dependent tablets coated with combination of two polymers Eudragit L100 and ethyl cellulose. The 150mg of core tablet of dried extract and lactose were prepared by wet granulation method. The compression coating was used in the polymer concentration of 150mg for both the layer as upper and lower coating tablet was investigated. The results showed that no release was found in 0.1 N HCl and pH 6.8 phosphate buffers for initial 5 hours and about 98.97% of the drug was released in pH 7.4 phosphate buffer in total 17 Hours. The in vitro release profiles of drug from the formulation could be best expressed first order kinetics as highest linearity (r²= 0.9943). The results of the present study have demonstrated that the time and pH dependent tablets system is a promising vehicle for preventing rapid hydrolysis in gastric environment and improving oral bioavailability of Embelin and Gallic acid for treatment of Helminthiasis.

Keywords: Embelin, Gallic acid, Vidangadi Churna, Colon targeted drug delivery.

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Authors: Jin Sun Oh, Kyung Ho Lee, S ang Gug Chung, Kyehan Rhee

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Microbubbbles incorporating ultrasound have been used to increase the efficacy of targeted drug delivery, because microstreaming induced by cavitating bubbles affects the drug perfusion into the target cells and tissues. In order to clarify the physical effects of microstreaming on drug perfusion into tissues, a preliminary experimental study of perfusion enhancement by a stably oscillating microbubble was performed. Microstreaming was induced by an oscillating bubble at 15 kHz, and perfusion of dye into an agar phantom was optically measured by histology on agar phantom. Surface color intensity and the penetration length of dye in the agar phantom were increased more than 70% and 30%, respectively, due to the microstreaming induced by an oscillating bubble. The mass of dye perfused into a tissue phantom for 30 s was increased about 80% in the phantom with an oscillating bubble. This preliminary experiment shows the physical effects of steady streaming by an oscillating bubble can enhance the drug perfusion into the tissues while minimizing the biological effects.

Keywords: Bubble, Mass Transfer, Microstreaming, Drug Delivery, Acoustic Wave.

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Authors: Dae Hwan Kang, Young-IL Jeong, Chung-Wook Chung

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pH-sensitive drug targeting using nanoparticles for cancer chemotherapy have been spotlighted in recent decades. Graft copolymer composed of poly (L-histidine) (PHS) and dextran (DexPHS) was synthesized and pH-sensitive nanoparticles were fabricated for pH-responsive drug delivery of doxorubicin (DOX). Nanoparticles of DexPHS showed pH-sensitive changes in particle sizes and drug release behavior, i.e. particle sizes and drug release rate were increased at acidic pH, indicating that DexPHS nanoparticles have pH-sensitive drug delivery potentials. Antitumor activity of DOX-incorporated DexPHS nanoparticles were studied using CT26 colorectal carcinoma cells. Results indicated that fluorescence intensity was higher at acidic pH than basic pH. These results indicated that DexPHS nanoparticles have pH-responsive drug targeting.

Keywords: pH-sensitive polymer, nanoparticles, block copolymer, poly (L-histidine).

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Authors: Yong Ren, Yaping Zhang

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A numerical model has been developed to investigate the thermally triggered release kinetics for drug delivery using phase change material as shell of microcapsules. Biocompatible material n-Eicosane is used as demonstration. PCM shell of microcapsule will remain in solid form after the drug is taken, so the drug will be encapsulated by the shell, and will not be released until the target body part of lesion is exposed to external heat source, which will thermally trigger the release kinetics, leading to solid-to-liquid phase change. The findings can lead to better understanding on the key effects influencing the phase change process for drug delivery applications. The facile approach to release drug from core/shell structure of microcapsule can be well integrated with organic solvent free fabrication of microcapsules, using double emulsion as template in microfluidic aqueous two phase system.

Keywords: Phase change material, drug release kinetics, double emulsion, microfluidics.

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Authors: E. R. Arakelova, S. G. Grigoryan, F. G. Arsenyan, N. S. Babayan, R. M. Grigoryan, N. K. Sarkisyan

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The nanotechnology offers some exciting possibilities in cancer treatment, including the possibility of destroying tumors with minimal damage to healthy tissue and organs by targeted drug delivery systems. Considerable achievements in investigations aimed at the use of ZnO nanoparticles and nanocontainers in diagnostics and antitumor therapy were described. However, there are substantial obstacles to the purposes to be achieved by the use of zinc oxide nanosize materials in antitumor therapy. Among the serious problems are the techniques of obtaining ZnO nanosize materials. The article presents a new vector delivery system for the known antitumor drug, doxorubicin in the form of polymeric (PEO, starch-NaCMC) hydrogels, in which nanosize ZnO film of a certain thickness are deposited directly on the drug surface on glass substrate by DC-magnetron sputtering of a zinc target. Anticancer activity in vitro and in vivo of those nanosize zinc oxide composites is shown.

Keywords: Anticancer activity, cancer specificity, doxorubicin, zinc oxide.

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Authors: Imran Khan Pathan, Anil Bhandari, Peeyush K. Sharma, Rakesh K. Patel, Suresh Purohit

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Floating tablets of Marichyadi Vati were developed with an aim to prolong its gastric residence time and increase the bioavailability of drug. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by wet granulation technique, using HPMC E50 LV act as Matrixing agent, Carbopol as floating enhancer, microcrystalline cellulose as binder, Sodium bi carbonate as effervescent agent with other excipients. The simplex lattice design was used for selection of variables for tablets formulation. Formulation was optimized on the basis of floating time and in vitro drug release. The results showed that the floating lag time for optimized formulation was found to be 61 second with about 97.32 % of total drug release within 3 hours. The vitro release profiles of drug from the formulation could be best expressed zero order with highest linearity r² = 0.9943. It was concluded that the gastroretentive drug delivery system can be developed for Marichyadi Vati containing Piperine to increase the residence time of the drug in the stomach and thereby increasing bioavailability.

Keywords: Piperine, Marichyadi Vati, Gastroretentive drug delivery, Floating tablet.

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Authors: Arpa Petchsomrit, Namfa Sermkaew, Ruedeekorn Wiwattanapatapee

Abstract:

Oil entrapped floating alginate beads of curcumin were developed and characterized. Cremophor EL, Cremophor RH and Tween 80 were utilized to improve the solubility of the drug. The oil-loaded floating gel beads prepared by emulsion gelation method contained sodium alginate, mineral oil and surfactant. The drug content and % encapsulation declined as the ratio of surfactant was increased. The release of curcumin from 1% alginate beads was significantly more than for the 2% alginate beads. The drug released from the beads containing 25% of Tween 80 was about 70% while a higher drug release was observed with the beads containing Cremophor EL or Cremohor RH (approximately 90%). The developed floating beads of curcumin powder with surfactant provided a superior drug release than those without surfactant. Floating beads based on oil entrapment containing the drug solubilized in surfactants is a new delivery system to enhance the dissolution of poorly soluble drugs.

Keywords: Alginate, curcumin, floating drug delivery, oil entrapped bead.

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Authors: M. Kumpugdee-Vollrath, M. Tabatabaeifar, M. Helmis

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Shellac is a natural polyester resin secreted by insects. Pectins are natural, non-toxic and water-soluble polysaccharides extracted from the peels of citrus fruits or the leftovers of apples. Both polymers are allowed for the use in the pharmaceutical industry and as a food additive. SSB Aquagold® is the aqueous solution of shellac and can be used for a coating process as an enteric or controlled drug release polymer. In this study, tablets containing 10 mg methylene blue as a model drug were prepared with a rotary press. Those tablets were coated with mixtures of shellac and one of the pectin different types (i.e. CU 201, CU 501, CU 701 and CU 020) mostly in a 2:1 ratio or with pure shellac in a small scale fluidized bed apparatus. A stable, simple and reproducible three-stage coating process was successfully developed. The drug contents of the coated tablets were determined using UV-VIS spectrophotometer. The characterization of the surface and the film thickness were performed with the scanning electron microscopy (SEM) and the light microscopy. Release studies were performed in a dissolution apparatus with a basket. Most of the formulations were enteric coated. The dissolution profiles showed a delayed or sustained release with a lagtime of at least 4 h. Dissolution profiles of coated tablets with pure shellac had a very long lagtime ranging from 13 to 17.9 h and the slopes were quite high. The duration of the lagtime and the slope of the dissolution profiles could be adjusted by adding the proper type of pectin to the shellac formulation and by variation of the coating amount. In order to apply a coating formulation as a colon delivery system, the prepared film should be resistant against gastric fluid for at least 2 h and against intestinal fluid for 4-6 h. The required delay time was gained with most of the shellac-pectin polymer mixtures. The release profiles were fitted with the modified model of the Korsmeyer-Peppas equation and the Hixson-Crowell model. A correlation coefficient (R²)> 0.99 was obtained by Korsmeyer-Peppas equation.

Keywords: Shellac, pectin, coating, fluidized bed, release, colon delivery system, kinetic, SEM, methylene blue.

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Authors: Kheireddine El-Boubbou

Abstract:

Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC₅₀ values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.

Keywords: Magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy.

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Authors: Anurag Gaur, Nidhi, Shashi Sharma

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Targeted drug delivery is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues. This improves efficacy of the while reducing side effects. In the present work, we investigate the effect of magnetic field, flow rate and particle concentration on the capturing of magnetic particles transported in a stent implanted fluidic channel. Iron oxide magnetic nanoparticles (Fe3O4) nanoparticles were synthesized via co-precipitation method. The synthesized Fe3O4 nanoparticles were added in the de-ionized (DI) water to prepare the Fe3O4 magnetic particle suspended fluid. This fluid is transported in a cylindrical tube of diameter 8 mm with help of a peristaltic pump at different flow rate (25-40 ml/min). A ferromagnetic coil of SS 430 has been implanted inside the cylindrical tube to enhance the capturing of magnetic nanoparticles under magnetic field. The capturing of magnetic nanoparticles was observed at different magnetic magnetic field, flow rate and particle concentration. It is observed that capture efficiency increases from 47-67% at magnetic field 2-5kG, respectively at particle concentration 0.6mg/ml and at flow rate 30 ml/min. However, the capture efficiency decreases from 65 to 44% by increasing the flow rate from 25 to 40 ml/min, respectively. Furthermore, it is observed that capture efficiency increases from 51 to 67% by increasing the particle concentration from 0.3 to 0.6 mg/ml, respectively.

Keywords: Capture efficiency, Implant assisted-Magnetic drug targeting (IA-MDT), Magnetic nanoparticles, in vitro study.

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Authors: P. S. Rajinikanth, Yeoh Suyu, Sanjay Garg

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The present study is aim to prepare and evaluate the selfnanoemulsifying drug delivery (SNEDDS) system of a poorly water soluble drug valsartan in order to achieve a better dissolution rate which would further help in enhancing oral bioavailability. The present research work describes a SNEDDS of valsartan using labrafil M 1944 CS, Tween 80 and Transcutol HP. The pseudoternary phase diagrams with presence and absence of drug were plotted to check for the emulsification range and also to evaluate the effect of valsartan on the emulsification behavior of the phases. The mixtures consisting of oil (labrafil M 1944 CS) with surfactant (tween 80), co-surfactant (Transcutol HP) were found to be optimum formulations. Prepared formulations were evaluated for its particle size distribution, nanoemulsifying properties, robustness to dilution, self emulsication time, turbidity measurement, drug content and invitro dissolution. The optimized formulations are further evaluated for heating cooling cycle, centrifugation studies, freeze thaw cycling, particle size distribution and zeta potential were carried out to confirm the stability of the formed SNEDDS formulations. The prepared formulation revealed t a significant improvement in terms of the drug solubility as compared with marketed tablet and pure drug.

Keywords: Self Emulsifying Drug Delivery System, Valsartan, Bioavailability, poorly soluble drug.

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Authors: M. Rahimnejad, B. Vahidi, B. Ebrahimi Hoseinzadeh, F. Yazdian, P. Motamed Fath, R. Jamjah

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In this study, we developed and simulated nano-drug delivery systems efficacy in compare to free drug prescription. Computational models can be utilized to accelerate experimental steps and control the experiments high cost. Molecular dynamics simulation (MDS), in particular NAMD was utilized to better understand the anti-cancer drug interaction with cell membrane model. Paclitaxel (PTX) and dipalmitoylphosphatidylcholine (DPPC) were selected for the drug molecule and as a natural phospholipid nanocarrier, respectively. This work focused on two important interaction parameters between molecules in terms of center of mass (COM) and van der Waals interaction energy. Furthermore, we compared the simulation results of the PTX interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane. The molecular dynamic analysis resulted in low energy between the nanocarrier and the cell membrane as well as significant decrease of COM amount in the nanocarrier and the cell membrane system during the interaction. Thus, the drug vehicle showed notably better interaction with the cell membrane in compared to free drug interaction with the cell membrane.

Keywords: Anti-cancer drug, center of Mass, interaction energy, molecular dynamics simulation, nanocarrier.

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Authors: Amlan Kumar Das, Avinash Marwal, Vikram Pareek

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Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI). The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III) / Iron (II) chloride with the leaf extract of Datura inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.

Keywords: Nanoparticles-Protein Hybrid, Magnetic Liposome.

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Authors: E. Aboutaleb, R. Dinarvand

Abstract:

The purpose of this work was to inspect the potential of vincristine-dextran complex loaded solid lipid nanoparticles for drug delivery to the brain. The nanoparticles were stained with a fluorescence dye and their plasma pharmacokinetic and brain concentrations were investigated following injection to rats. The result revealed a significant improvement in the plasma concentration profile of the SLN injected animals as well as a sharp increased concentration in the brains.

Keywords: Brain, Coumarin-6, Nanoparticles, SLN.

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Authors: Papon Thamvasupong, Kwanchanok Viravaidya-Pasuwat

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Osteoarthritis affects a lot of people worldwide. Local injection of glucosamine is one of the alternative treatment methods to replenish the natural lubrication of cartilage. However, multiple injections can potentially lead to possible bacterial infection. Therefore, a drug delivery system is desired to reduce the frequencies of injections. A hydrogel is one of the delivery systems that can control the release of drugs. Thermo-reversible hydrogels can be beneficial to the drug delivery system especially in the local injection route because this formulation can change from liquid to gel after getting into human body. Once the gel is in the body, it will slowly release the drug in a controlled manner. In this study, various formulations of Pluronic-based hydrogels were synthesized for the controlled release of glucosamine. One of the challenges of the Pluronic controlled release system is its fast dissolution rate. To overcome this problem, alginate and calcium sulfate (CaSO₄) were added to the polymer solution. The characteristics of the hydrogels were investigated including the gelation temperature, gelation time, hydrogel dissolution and glucosamine release mechanism. Finally, a mathematical model of glucosamine release from Pluronic-alginate-hyaluronic acid hydrogel was developed. Our results have shown that crosslinking Pluronic gel with alginate did not significantly extend the dissolution rate of the gel. Moreover, the gel dissolution profiles and the glucosamine release mechanisms were best described using the zeroth-order kinetic model, indicating that the release of glucosamine was primarily governed by the gel dissolution.

Keywords: Controlled release, drug delivery system, glucosamine, Pluronic® F-127, thermoreversible hydrogel.

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Authors: Simona Dostalova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

Abstract:

Various nanomaterials can be used as a drug delivery vehicles in nanomedicine, called nanocarriers. They can either be organic or inorganic, synthetic or natural-based. Although synthetic nanocarriers are easier to produce, they can often be toxic for the organism and thus not suitable for use in treatment. From naturalbased nanocarriers, the most commonly used are protein cages or viral capsids. In this work, virus bacteriophage λ was used for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2% maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000×g and 4°C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 μg·mL-1). Free drug molecules were removed by filtration. The encapsulation was verified using the absorbance for doxorubicin and atomic absorption spectrometry for platinum cytostatics. The amount of encapsulated drug linearly increased with the increasing concentration of applied drug with the determination coefficient R2=0.989 for doxorubicin; R2=0.967 for cisplatin; R2=0.989 for carboplatin and R2=0.996 for oxaliplatin. The overall encapsulation efficiency was calculated as 50% for doxorubicin; 8% for cisplatin; 6% for carboplatin and 10% for oxaliplatin.

Keywords: Bacteriophage λ, doxorubicin, platinum cytostatics, protein-based nanocarrier, viral capsid.

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Authors: Mohammad Sadeghi, Behrouz Heidari, Korush Montazeri

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In this article, we synthesize a novel chitosan -based superabsorbent hydrogel via graft copolymerization of mixtures acrylic acid (AA) and N-vinyl pyrollidon onto chitosan backbones. The polymerization reaction was carried out in an aqueous medium and in the presence of ammonium persulfate (APS) as an initiator and N,N'-methylene bisacrylamide (MBA) as a crosslinker.The hydrogel structures were confirmed by FTIR spectroscopy. The swelling behavior of these absorbent polymers was also investigated in various salt solutions. Results indicated that the swelling capacity decreased with an increase in the ionic strength of the swelling medium. Furthermore, the swelling of superabsorbing hydrogels was examined in solutions with pH values ranging between 1.0 and 13.0. It showed a reversible pH-responsive behavior at pHs 2.0 and 8.0. This on-off switching behavior makes the synthesized hydrogels as an excellent candidate for controlled delivery of bioactive agents.

Keywords: chitosan, acrylic acid, N-vinyl pyrollidon, hydrogel, Ibuprofen's drug delivery

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Authors: M. Kumpugdee-Vollrath, J.-P. Krause, S. Bürk

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Most of the drugs used for pharmaceutical purposes are poorly water-soluble drugs. About 40% of all newly discovered drugs are lipophilic and the numbers of lipophilic drugs seem to increase more and more. Drug delivery systems such as nanoparticles, micelles or liposomes are applied to improve their solubility and thus their bioavailability. Besides various techniques of solubilization, oil-in-water emulsions are often used to incorporate lipophilic drugs into the oil phase. To stabilize emulsions surface active substances (surfactants) are generally used. An alternative method to avoid the application of surfactants was of great interest. One possibility is to develop O/W-emulsion without any addition of surface active agents or the so called “surfactant-free emulsion or SFE”. The aim of this study was to develop and characterize SFE as a drug carrier by varying the production conditions. Lidocaine base was used as a model drug. The injection method was developed. Effects of ultrasound as well as of temperature on the properties of the emulsion were studied. Particle sizes and release were determined. The long-term stability up to 30 days was performed. The results showed that the surfactant-free O/W emulsions with pharmaceutical oil as drug carrier can be produced.

Keywords: Emulsion, lidocaine, Miglyol, size, surfactant, light scattering, release, injection, ultrasound, stability.

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Authors: Alfred L. Guiffrida

Abstract:

A review of the literature on supply chain delivery models which use delivery windows to measure delivery performance is presented. The review herein serves to meet the following objectives: (i) provide a synthesis of previously published literature on supply chain delivery performance models, (ii) provide in one paper a consolidation of research that can serve as a single source to keep researchers up to date with the research developments in supply chain delivery models, and (iii) identify gaps in the modeling of supply chain delivery performance which could stimulate new research agendas.

Keywords: Delivery performance, Delivery window, Supply chain delivery models, Supply chain performance.

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Authors: Simone Galati, Adriano Troia

Abstract:

Ultrasound (US) is widely used in medical field for a variety diagnostic techniques but, in recent years, it has also been creating great interest for therapeutic aims. Regarding drug delivery, the use of US as an activation source provides better spatial delivery confinement and limits the undesired side effects. However, at present there is no complete characterization at a fundamental level of the different signals produced by sono-activated nanocarriers. Therefore, the aim of this study is to obtain a metrological characterization of the cavitation phenomena induced by US through three parallel investigation approaches. US was focused into a channel of a customized phantom in which a solution with oxygen-loaded nanodroplets (OLNDs) was led to flow and the cavitation activity was monitored. Both quantitative and qualitative real-time analysis were performed giving information about the dynamics of bubble formation, oscillation and final implosion with respect to the working acoustic pressure and the type of nanodroplets, compared with pure water. From this analysis a possible interpretation of the observed results is proposed.

Keywords: Cavitation, Drug Delivery, Nanodroplets, Ultrasound.

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Authors: Emma R. Arakelova, Stepan G. Grigoryan, Ashot M. Khachatryan, Karapet E. Avjyan, Lilia M. Savchenko, Flora G. Arsenyan

Abstract:

The paper presents a new drugs delivery system, based on the thin film technology. As a model antitumor drug, highly toxic doxorubicin is chosen. The system is based on the technology of obtaining zinc oxide composite of doxorubicin by deposition of nanosize ZnO films on the surface of doxorubicin coating on glass substrate using DC magnetron sputtering of zinc targets in Ar:O₂ medium at room temperature. For doxorubicin zinc oxide compositions in the form of coatings and gels with 180-200nm thick ZnO films, higher (by a factor 2) in vivo (ascitic Ehrlich's carcinoma) antitumor activity is observed at low doses of doxorubicin in comparison with that of the initial preparation at therapeutic doses. The vector character of the doxorubicin zinc oxide composite transport to tumor tissues ensures the increase in antitumor activity as well as decrease of toxicity in comparison with the initial drug.

Keywords: Antitumor activity, doxorubicin, DC magnetron sputtering, zinc oxide.

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Authors: Hong Yi Huang, Wei Ti Kuo, Yi You Huang

Abstract:

Non-viral gene carriers composed of biodegradable polymers or lipids have been considered as a safer alternative for gene carriers over viral vectors. We have developed multi-functional nano-micelles for both drug and gene delivery application. Polyethyleneimine (PEI) was modified by grafting stearic acid (SA) and formulated to polymeric micelles (PEI-SA) with positive surface charge for gene and drug delivery. Our results showed that PEI-SA micelles provided high siRNA binding efficiency. In addition, siRNA delivered by PEI-SA carriers also demonstrated significantly high cellular uptake even in the presence of serum proteins. The post-transcriptional gene silencing efficiency was greatly improved by the polyplex formulated by 10k PEI-SA/siRNA. The amphiphilic structure of PEI-SA micelles provided advantages for multifunctional tasks; where the hydrophilic shell modified with cationic charges can electrostatically interact with DNA or siRNA, and the hydrophobic core can serve as payloads for hydrophobic drugs, making it a promising multifunctional vehicle for both genetic and chemotherapy application.

Keywords: polyethyleneimine, gene delivery, micelles, siRNA

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Authors: Hsuan-Chia Yang, Yan-Jhih Haung, Yu-Chuan Li

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Researchers of drug-drug interaction alert systems have often suggested that there were high overridden rate for alerts and also too false alerts. However, research about decreasing false alerts is scant. Therefore, the aim of this article attempts to proactive identification of false alert for drug-drug interaction and provide solution to decrease false alerts. This research involved retrospective analysis prescribing database and calculated false alert rate by using MYSQL and JAVA. Results of this study showed 17% of false alerts and the false alert rate in the hospitals (37%) was more than in the clinics. To conclude, this study described the importance that drug-drug interaction alert system should not only detect drug name but also detect frequency or route, as well as in providing solution to decrease false alerts.

Keywords: drug-drug interaction, proactive identification, false alert

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Authors: Hadi Hasanzadeh, Manijhe Mokhtari-Dizaji, S.Zahra Bathaie, Zuhair M. Hassan, Hamid R. Miri, Mahbobe Alamolhoda, Vahid Nilchiani, Hamid Goudarzi

Abstract:

The nanosized polymeric micelles release the drug due to acoustic cavitation, which is enhanced in dual frequency ultrasonic fields. In this study, adult female Balb/C mice were transplanted with spontaneous breast adenocarcinoma tumors and were injected with a dose of 1.3 mg/kg doxorubicin in one of three forms: free doxorubicin, micellar doxorubicin without sonication and micellar doxorubicin with sonication. To increase cavitation yield, the tumor region was sonicated with low level dual frequency of 3 MHz and 28 kHz. The animals were sacrificed 24 h after injection, and their tumor, heart, spleen, liver, kidneys and plasma were separated and homogenized. The drug content in their tumor, heart, spleen, liver, kidneys and plasma was determined using tissue fluorimetry. The results show that in the group that received micellar doxorubicin with sonication, the drug concentration in the tumor tissue was nine and three times higher than in the free doxorubicin group and the micellar doxorubicin without sonication group, respectively. In the micellar doxorubicin with sonication group, the drug concentration in other tissues was lower than other groups (p<0.05). We conclude that dual frequency sonication improves drug release from micelles and increases the drug uptake by tumors due to sonoporation.

Keywords: Nanomicelles, Dual frequency ultrasound, Drug delivery

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Authors: G. Spada, E. Gavini, P. Giunchedi

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Aim of this work was to compare the efficacy of two loading methods of proteins onto polymeric nanocarriers: adsorption and encapsulation methods. Preliminary studies of protein loading were done using Bovine Serum Albumin (BSA) as model protein. Nanocarriers were prepared starting from polylactic co-glycolic acid (PLGA) polymer; production methods used are two different variants of emulsion evaporation method. Nanoparticles obtained were analyzed in terms of dimensions by Dynamic Light Scattering and Loading Efficiency of BSA by Bradford Assay. Loaded nanoparticles were then submitted to in-vitro protein dissolution test in order to study the effect of the delivery system on the release rate of the protein.

Keywords: Drug delivery, nanoparticles, PLGA, proteinadsorption, protein encapsulation.

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Authors: Muhammad Waseem Ashraf, Shahzadi Tayyaba, Nitin Afzulpurkar, Asim Nisar, Adisorn Tuantranont, Erik L J Bohez

Abstract:

In this paper, design, fabrication and coupled multifield analysis of hollow out-of-plane silicon microneedle array with piezoelectrically actuated microfluidic device for transdermal drug delivery (TDD) applications is presented. The fabrication process of silicon microneedle array is first done by series of combined isotropic and anisotropic etching processes using inductively coupled plasma (ICP) etching technology. Then coupled multifield analysis of MEMS based piezoelectrically actuated device with integrated 2×2 silicon microneedle array is presented. To predict the stress distribution and model fluid flow in coupled field analysis, finite element (FE) and computational fluid dynamic (CFD) analysis using ANSYS rather than analytical systems has been performed. Static analysis and transient CFD analysis were performed to predict the fluid flow through the microneedle array. The inlet pressure from 10 kPa to 150 kPa was considered for static CFD analysis. In the lumen region fluid flow rate 3.2946 μL/min is obtained at 150 V for 2×2 microneedle array. In the present study the authors have performed simulation of structural, piezoelectric and CFD analysis on three dimensional model of the piezoelectrically actuated mcirofluidic device integrated with 2×2 microneedle array.

Keywords: Coupled multifield, finite element analysis, hollow silicon microneedle, transdermal drug delivery.

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Authors: Parisa Shirzadeh

Abstract:

Drug delivery systems in which drugs are traditionally used, multi-stage and at specified intervals by patients, do not meet the needs of the world's up-to-date drug delivery. In today's world, we are dealing with a huge number of recombinant peptide and protean drugs and analogues of hormones in the body, most of which are made with genetic engineering techniques. Most of these drugs are used to treat critical diseases such as cancer. Due to the limitations of the traditional method, researchers sought to find ways to solve the problems of the traditional method to a large extent. Following these efforts, controlled drug release systems were introduced, which have many advantages. Using controlled release of the drug in the body, the concentration of the drug is kept at a certain level, and in a short time, it is done at a higher rate. Graphene is a natural material that is biodegradable, non-toxic, natural and wide surfaces of graphene plates makes it more effective to modify graphene than carbon nanotubes. Graphene oxide is often synthesized using concentrated oxidizers such as sulfuric acid, nitric acid, and potassium permanganate based on Hummer method. graphene oxide is very hydrophilic and easily dissolves in water and creates a stable solution. Graphene oxide (GO) has been modified by chitosan (CS) covalently, developed for control release of doxorubicin (DOX). In this study, GO is produced by the hummer method under acidic conditions. Then, it is chlorinated by oxalyl chloride to increase its reactivity against amine. After that, in the presence of CS, the amino reaction was performed to form amide transplantation, and the DOX was connected to the carrier surface by π-π interaction in buffer phosphate. GO, GO-CS, and GO-CS-DOX were characterized by FT-IR and TGA to recognize new functional groups which show the new bonding of CS to GO, RAMA and SEM to recognize size of layers that show changing in size and number of layers. The ability to load and release is determined by UV-Visible spectroscopy. The loading result showed a high capacity of DOX absorption (99%) and pH dependence identified as a result of DOX release from GO-CS nanosheet at pH 5.3 and 7.4, which show a fast release rate in acidic conditions.

Keywords: Graphene oxide, chitosan, nanosheet, controlled drug release, doxorubicin.

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Authors: Jolanta Pulit-Prociak, Olga Długosz, Marcin Banach

Abstract:

The toxicity of bare zinc oxide nanoparticles used as drug carriers may be the result of releasing zinc ions. Thus, zinc oxide nanoparticles modified with galactose were obtained. The process of their formation was conducted in the microwave field. The physicochemical properties of the obtained products were studied. The size and electrokinetic potential were defined by using dynamic light scattering technique. The crystalline properties were assessed by X-ray diffractometry. In order to confirm the formation of the desired products, Fourier-transform infrared spectroscopy was used. Releasing of zinc ions from the prepared products when comparing to the bare oxide was analyzed. It was found out that modification of zinc oxide nanoparticles with galactose limits the releasing of zinc ions which are responsible for the toxic effect of the whole carrier-drug conjugate.

Keywords: Nanomaterials, zinc oxide, drug delivery system, toxicity.

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Authors: C. Hönnscheidt, R. Krull

Abstract:

Oxidative stress makes up common incidents in eukaryotic metabolism. The presence of diverse components disturbing the equilibrium during oxygen metabolism increases oxidative damage unspecifically in living cells. Body´s own ubiquinone (Q10) seems to be a promising drug in defending the heightened appearance of reactive oxygen species (ROS). Though, its lipophilic properties require a new strategy in drug formulation to overcome their low bioavailability. Consequently, the manufacture of heterogeneous nanodispersions is in focus for medical applications. The composition of conventional nanodispersions is made up of a drug-consisting core and a surfactive agent, also named as surfactant. Long-termed encapsulation of the surfactive components into tissues might be the consequence of the use during medical therapeutics. The potential of provoking side-effects is given by their nonbiodegradable properties. Further improvements during fabrication process use the incorporation of biodegradable components such as modified γ-polyglutamic acid which decreases the potential of prospective side-effects.

Keywords: Biopolymers, γ-Polyglutamic acid, Oxidative stress, Ubiquinone.

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Authors: D. Bhaskar, N. R. Wadehra, M. Gulati, A. Narula, R. Vishnu, G. Katyal

Abstract:

With drug resistance becoming widespread in Plasmodium falciparum infections, the development of the alternative drugs is the desired strategy for prevention and cure of malaria. Three drug targets were selected to screen promising drug molecules from the GSK library of 13469 molecules. Using an in silico structure-based drug designing approach, the differences in binding energies of the substrate and inhibitor were exploited between target sites of parasite and human to design a drug molecule against Plasmodium. The docking studies have shown several promising molecules from GSK library with more effective binding as compared to the already known inhibitors for the drug targets. Though stronger interaction has been shown by several molecules as compared to the reference, few molecules have shown the potential as drug candidates though in vitro studies are required to validate the results. In case of thymidylate synthase-dihydrofolatereductase (TS-DHFR), three compounds have shown promise for future studies as potential drugs.

Keywords: Drug resistance, Drug targets, In silico studies, Plasmodium falciparum.

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