scholarly journals IMPROVEMENT OF THE MICROFLUIDIC DEVICE FOR THE GENERATION OF MONODISPERSE MICROBUBBLES AS DRUG TRANSPORT SYSTEMS

2021 ◽  
Vol 9 (8) ◽  
pp. 109-124
Author(s):  
Araújo Filho W. D ◽  
Chaves Antônio A. G. S ◽  
Dos Santos F. F. ◽  
A. F. Santos Junior
Keyword(s):  
Drug Transport ◽  
Structural Characteristics ◽  
Drug Carrier ◽  
Ultrasonic Field ◽  
Single Step ◽  
Transport Systems ◽  
Promising Alternative ◽  
Fluidic Devices ◽  
Final Composition ◽  
Localized Treatment

INTRODUCTION: The localized delivery of drugs has been established since the early eighties of the 20th century as a promising alternative for the localized treatment of tumours, based on the mitigation of side effects produced by traditional methods, notably the administration of chemotherapy by systemic route. Countless scientific works have been dealing with this theme in an attempt to make this therapeutic technique viable and accessible. One of the ways to take the drug to the chosen site is through the use of microbubbles as drug carrier units activated through an ultrasonic field with adequate wavelength and frequency. Therefore, these units must have very peculiar characteristics, such as dimensions, homogeneity, echogenicity and structural characteristics, in addition to the ability to take the therapeutic vector intact to the desired location. In the generation of microbubbles, microfluidic devices of different geometries and different configurations are used, according to the state of the art related to this theme. DEVELOPMENT: In this work the technique used is the fabrication of micro fluidic devices using 3D printing. With this technique, it is possible to manufacture the devices in a single step, eliminating time-consuming and more complex intermediate procedures. The devices were manufactured using an Object Eden 250 printer, using the transparent resin VeroClear®. With these devices it was possible to produce microbubbles with diameters of the order of 16-73 µm with degrees of poly dispersion less than 1%. However, there are difficulties to be overcome, notably with regard to the final composition of the devices. Due to the physical characteristics of the microbubble, notably in relation to its lipid coating layer, the search for drug transport systems is an important strategy.  CONCLUSION: In this work, an account of these difficulties will be made, in addition to the proposition of alternatives to overcome them. Additionally, compatible drugs will be suggested to be attached to microbubbles according to their structural composition.

scholarly journals Molecular Properties of Bacterial Multidrug Transporters

2000 ◽  
Vol 64 (4) ◽  
pp. 672-693 ◽  
Author(s):  
Monique Putman ◽  
Hendrik W. van Veen ◽  
Wil N. Konings
Keyword(s):  
Drug Transport ◽  
Structural Characteristics ◽  
Substrate Binding ◽  
Regulatory Protein ◽  
Binding Pocket ◽  
Drug Binding ◽  
Transport Systems ◽  
Dimensional Structure ◽  
Detailed Knowledge ◽  
Multidrug Transporters

SUMMARY One of the mechanisms that bacteria utilize to evade the toxic effects of antibiotics is the active extrusion of structurally unrelated drugs from the cell. Both intrinsic and acquired multidrug transporters play an important role in antibiotic resistance of several pathogens, including Neisseria gonorrhoeae, Mycobacterium tuberculosis, Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Vibrio cholerae. Detailed knowledge of the molecular basis of drug recognition and transport by multidrug transport systems is required for the development of new antibiotics that are not extruded or of inhibitors which block the multidrug transporter and allow traditional antibiotics to be effective. This review gives an extensive overview of the currently known multidrug transporters in bacteria. Based on energetics and structural characteristics, the bacterial multidrug transporters can be classified into five distinct families. Functional reconstitution in liposomes of purified multidrug transport proteins from four families revealed that these proteins are capable of mediating the export of structurally unrelated drugs independent of accessory proteins or cytoplasmic components. On the basis of (i) mutations that affect the activity or the substrate specificity of multidrug transporters and (ii) the three-dimensional structure of the drug-binding domain of the regulatory protein BmrR, the substrate-binding site for cationic drugs is predicted to consist of a hydrophobic pocket with a buried negatively charged residue that interacts electrostatically with the positively charged substrate. The aromatic and hydrophobic amino acid residues which form the drug-binding pocket impose restrictions on the shape and size of the substrates. Kinetic analysis of drug transport by multidrug transporters provided evidence that these proteins may contain multiple substrate-binding sites.

Copper Transport Systems are Involved in Multidrug Resistance and Drug Transport

2008 ◽  
Vol 15 (30) ◽  
pp. 3268-3278 ◽  
Author(s):  
Tatsuhiko Furukawa ◽  
Masaharu Komatsu ◽  
Ryuji Ikeda ◽  
Kazutake Tsujikawa ◽  
Shin-ichi Akiyama
Keyword(s):  
Multidrug Resistance ◽  
Drug Transport ◽  
Copper Transport ◽  
Transport Systems

scholarly journals Fusogenics

2010 ◽  
Vol 16 (1) ◽  
pp. 90-100 ◽  
Author(s):  
Jeannick Cizeau ◽  
Marianne G. P. Torres ◽  
Sharla G. Cowling ◽  
Stacy Stibbard ◽  
Arjune Premsukh ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Screening Method ◽  
Antibody Fragment ◽  
Vital Role ◽  
Single Step ◽  
Functional Assay ◽  
Plant Toxin ◽  
Promising Alternative ◽  
Pseudomonas Exotoxin A ◽  
Normal Tissues

Antibody-based therapeutics play a vital role in the treatment of certain cancers; however, despite commercial success, various strategies are being pursued to increase their potency and hence improve patient outcomes. The use of antibodies to deliver a cytotoxic payload offers a promising alternative for more efficacious therapies. Immunotoxins are composed of an internalizing antibody fragment linked to a bacterial or plant toxin. Once internalized, the payload, such as Pseudomonas exotoxin A (PE), blocks protein synthesis and induces apoptosis. Typically, immunotoxins are developed by first isolating a tumor-specific antibody, which is then either chemically linked to a toxin or reengineered as a fusion protein. Here, the authors describe the development of Fusogenics, an immunotoxin-based screening method that selects internalizing tumor-specific antibodies using a functional assay. Selected immune library clones were characterized and shown to be selective against normal tissues and specific to tumor tissues. In summary, the Fusogenics immunotoxin platform represents a unique, single-step selection approach combining specificity and functionality to isolate novel internalizing tumor-specific antibody fragments with potential for direct clinical application in the treatment of cancer.

scholarly journals Development of polycationic amphiphilic cyclodextrin nanoparticles for anticancer drug delivery

2017 ◽  
Vol 8 ◽  
pp. 1457-1468 ◽  
Author(s):  
Gamze Varan ◽  
Juan M Benito ◽  
Carmen Ortiz Mellet ◽  
Erem Bilensoy
Keyword(s):  
Drug Delivery ◽  
Cell Line ◽  
Anticancer Drug ◽  
Drug Delivery Systems ◽  
Drug Carrier ◽  
Delivery Systems ◽  
Loading Capacity ◽  
Promising Alternative ◽  
Cytotoxicity Studies ◽  
Amphiphilic Cyclodextrin

Background: Paclitaxel is a potent anticancer drug that is effective against a wide spectrum of cancers. To overcome its bioavailability problems arising from very poor aqueous solubility and tendency to recrystallize upon dilution, paclitaxel is commercially formulated with co-solvents such as Cremophor EL® that are known to cause serious side effects during chemotherapy. Amphiphilic cyclodextrins are favored oligosaccharides as drug delivery systems for anticancer drugs, having the ability to spontaneously form nanoparticles without surfactant or co-solvents. In the past few years, polycationic, amphiphilic cyclodextrins were introduced as effective agents for gene delivery in the form of nanoplexes. In this study, the potential of polycationic, amphiphilic cyclodextrin nanoparticles were evaluated in comparison to non-ionic amphiphilic cyclodextrins and core–shell type cyclodextrin nanoparticles for paclitaxel delivery to breast tumors. Pre-formulation studies were used as a basis for selecting the suitable organic solvent and surfactant concentration for the novel polycationic cyclodextrin nanoparticles. The nanoparticles were then extensively characterized with particle size distribution, polydispersity index, zeta potential, drug loading capacity, in vitro release profiles and cytotoxicity studies. Results: Paclitaxel-loaded cyclodextrin nanoparticles were obtained in the diameter range of 80−125 nm (depending on the nature of the cyclodextrin derivative) where the smallest diameter nanoparticles were obtained with polycationic (PC) βCDC6. A strong positive charge also helped to increase the loading capacity of the nanoparticles with paclitaxel up to 60%. Interestingly, cyclodextrin nanoparticles were able to stabilize paclitaxel in aqueous solution for 30 days. All blank cyclodextrin nanoparticles were demonstrated to be non-cytotoxic against L929 mouse fibroblast cell line. In addition, paclitaxel-loaded nanoparticles have a significant anticancer effect against MCF-7 human breast cancer cell line as compared with a paclitaxel solution in DMSO. Conclusion: According to the results of this study, both amphiphilic cyclodextrin derivatives provide suitable nanometer-sized drug delivery systems for safe and efficient intravenous paclitaxel delivery for chemotherapy. In the light of these studies, it can be said that amphiphilic cyclodextrin nanoparticles of different surface charge can be considered as a promising alternative for self-assembled nanometer-sized drug carrier systems for safe and efficient chemotherapy.

GENIPIN CROSSLINKED DRUG–GELATIN COMPOSITE FOR DRUG TRANSPORT AND CYTOCOMPATIBILITY

2011 ◽  
Vol 23 (02) ◽  
pp. 113-118 ◽  
Author(s):  
Goutam Thakur ◽  
Analava Mitra ◽  
Amit Basak
Keyword(s):  
Drug Transport ◽  
Drug Carrier ◽  
Harmful Effect ◽  
Initial Increase ◽  
Crossover Point ◽  
Porous Network ◽  
Cell Compatibility ◽  
Viability Assay ◽  
Drug Concentrations

Gelatin-based drug carrier matrices have emerged as very promising class of delivery system. The purpose of this investigation was to develop drug loaded gelatin-based gels (composites). Gelatin matrices were crosslinked with genipin, a naturally occurring crosslinker for the release of indomethacin. Indomethacin, a low molecular weight and moderately hydrophobic, anti-inflammatory agent was incorporated into the gelatin matrices to form drug loaded gel composites for the release study. The gels were subjected to temperature-dependent oscillatory rheology. The result showed pouring temperature in the range of ~31–34°C for the un-crosslinked gels while the crosslinked gels did not show crossover point. Gels were studied for surface morphology using scanning electron microscopy and a porous network structure was observed. The release of indomethacin from the gels indicated an initial increase in the release rate with the increase in drug concentrations. It was observed that drug composites with higher drug concentration exhibited higher drug transport. Swelling and crosslinking played a crucial role in regulating the drug transport. Further, viability assay suggested biocompatibility of these matrices in vitro. Gel in vitro cell compatibility using live dead assay evaluated with AH-927 cell line indicated normal cell proliferation without any harmful effect and thus suggesting appropriateness of crosslinked composites as potential drug carrier.

scholarly journals Σύνθεση και χαρακτηρισμός πρωτότυπων ολιγομερών κυκλοδεξτρινών για μεταφορά φαρμάκων

2014 ◽  
Author(s):  
Μαλαματένια Μανουηλίδου
Keyword(s):  
Binding Capacity ◽  
Drug Carrier ◽  
Aqueous Solubility ◽  
Single Step ◽  
Drug Formulation ◽  
Water Soluble ◽  
Amide Bond ◽  
Mild Conditions ◽  
Order Of Magnitude ◽  
High Yields

Cyclodextrins (CDs) are cyclic hollow oligosaccharide molecules that form water solublehost-guest systems, with many applications in drug formulation and delivery. CDoligomers have been previously studied due to the interest towards smart hosts withenhanced molecular recognition and binding capacity as sensors, catalysts, enzymemimics, photoreactive systems, etc. The aim of this dissertation was to prepare αCDoligomers for drug inclusion and transport with criteria: (i) ease of preparation, inaqueous media, in short steps, under mild conditions and in good yields, (ii) to obtainoligomers with satisfactory aqueous solubility and full availability of the CD cavities (iv)to achieve multiple binding with strengths better or comparable to those of parent αCD.The copper catalyzed azide-alkyne cyclization (CuAAC) reaction was utilized to preparea new water soluble cyclodextrin trimer very efficiently. The trimer engulfed threemolecules of a model guest and satisfactorily solubilized the chemotherapeutictamoxifen citrate and its active metabolite, N-desmethyltamoxifen, increasing theirsolubility by >1 order of magnitude. Moreover, for the first time the bioorthogonalStaudinger Ligation was applied to prepare αCD-dimers. For this purpose, a doublyactive linker was specifically developed that enabled dimer preparation in a single step,in aqueous/organic media, under mild conditions and with high yields. The aboveprepared products were studied in detail by NMR spectroscopy and were found toadopt, by self-inclusion, a closed conformation in aqueous solution, which completelyopened up in the presence of a suitable guest, leaving the cavities fully available to formthe corresponding inclusion complexes. Titration and DOSY NMR experimentsconfirmed the above and showed that the dimeric species form slowly diffusingaggregates in water, that in the presence of the guest partially disperse. The StaudingerLigation could thus become the method of choice for preparing CD dimers.Solubilization of practically insoluble N-desmethyl-tamoxifen was also achieved to 0.3mM. Moreover, CD dimers prepared via amide bond formation were less efficient andrequired harsh conditions. Finally, SNO-αCD derivatives were prepared andcharacterized as bimodal NO and drug carrier systems.

scholarly journals The Influence of Lignin Diversity on the Structural and Thermal Properties of Polymeric Microspheres Derived from Lignin, Styrene, and/or Divinylbenzene

Materials ◽  
2019 ◽  
Vol 12 (18) ◽  
pp. 2847 ◽  
Author(s):  
Marta Goliszek ◽  
Beata Podkościelna ◽  
Olena Sevastyanova ◽  
Barbara Gawdzik ◽  
Artur Chabros
Keyword(s):  
Thermal Properties ◽  
Structural Characteristics ◽  
Polymer Network ◽  
Eucalyptus Grandis ◽  
Nitrogen Adsorption ◽  
Optical Microscope ◽  
Scanning Calorimetry ◽  
Promising Alternative ◽  
Synthetic Materials ◽  
The Impact

This work investigates the impact of lignin origin and structural characteristics, such as molecular weight and functionality, on the properties of corresponding porous biopolymeric microspheres obtained through suspension-emulsion polymerization of lignin with styrene (St) and/or divinylbenzene (DVB). Two types of kraft lignin, which are softwood (Picea abies L.) and hardwood (Eucalyptus grandis), fractionated by common industrial solvents, and related methacrylates, were used in the synthesis. The presence of the appropriate functional groups in the lignins and in the corresponding microspheres were investigated by attenuated total reflectance Fourier transform infrared spectroscopy (ATR/FT-IR), while the thermal properties were studied by differential scanning calorimetry (DSC). The texture of the microspheres was characterized using low-temperature nitrogen adsorption. The swelling studies were performed in typical organic solvents and distilled water. The shapes of the microspheres were confirmed with an optical microscope. The introduction of lignin into a St and/or DVB polymeric system made it possible to obtain highly porous functionalized microspheres that increase their sorption potential. Lignin methacrylates created a polymer network with St and DVB, whereas the unmodified lignin acted mainly as an eco-friendly filler in the pores of St-DVB or DVB microspheres. The incorporation of biopolymer into the microspheres could be a promising alternative to a modification of synthetic materials and a better utilization of lignin.

scholarly journals Chia (Salvia hispanica L.) a Promising Alternative for Conventional and Gelled Emulsions: Technological and Lipid Structural Characteristics

Gels ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. 19
Author(s):  
Irene Muñoz-González ◽  
Esther Merino-Álvarez ◽  
Marina Salvador ◽  
Tatiana Pintado ◽  
Claudia Ruiz-Capillas ◽  
...  
Keyword(s):  
Soy Protein ◽  
Structural Characteristics ◽  
Acyl Chain ◽  
Soy Protein Isolate ◽  
Protein Isolate ◽  
Salvia Hispanica ◽  
Water Binding ◽  
Promising Alternative ◽  
Chain Mobility ◽  
Salvia Hispanica L

Chia (Salvia hispanica L.) is an oilseed plant which contains proteins of high biological value and other healthy components with interesting technological properties. For these reasons, chia could be a promising option for the formation and stabilization of oil-in-water emulsions. The aim of this study is to evaluate the potential of chia protein (from chia flour) in the formation of emulsions. To that end, composition and technological and structural properties determined by infrared spectroscopy were investigated in conventional (EC) and gelled (EGC) emulsions with chia and compared with their corresponding soy protein emulsions with the same protein content [conventional (ES) or gelled (EGS)] used as reference. All emulsions containing chia had better fat and water binding properties than those elaborated with soy protein isolate (SPI). The color of the emulsions varied significantly depending on whether the emulsions were made with chia or SPI. EGS and EGC exhibited the greatest (p < 0.05) penetration force values, being EGC the firmest (p < 0.05). Depending on the type of emulsion, Attenuated Total Reflectance (ATR)-FTIR Spectroscopy revealed differences in their lipid structure and interaction in terms of lipid acyl chain mobility (order/disorder) and emulsion droplet size. These structural characteristics could be related to the textural behavior of emulsions.

Performance/Economics Comparison of Sensible and Thermochemical Energy Transport Systems for Solar Thermal Dish Applications

1987 ◽  
Vol 109 (3) ◽  
pp. 227-234 ◽  
Author(s):  
J. F. Muir
Keyword(s):  
Energy Cost ◽  
Energy Transport ◽  
Cost Effective ◽  
Heat Losses ◽  
Solar Thermal ◽  
Transport Systems ◽  
Promising Alternative ◽  
Solar Systems ◽  
Point Of Use

A major challenge facing the development of distributed receiver solar systems is the efficient transport of high temperature thermal energy from the collectors to the point of use. As receiver temperatures increase, conventional sensible (SEN) energy transport methods become less attractive because of increased heat losses and insulation costs. A promising alternative that is particularly attractive for the high temperatures characteristic of paraboloidal dishes and the extensive piping associated with large collector fields is the concept of themochemical (TC) energy transport. Estimates of the performance and economics of 4 SEN and 2 TC transport systems for a dish collector field are compared at 4 delivery temperatures ranging from 400 to 815° C. On the basis of levelized energy cost (LEC), there is no clear choice between SEN and TC energy transport at 400°C. At higher output temperatures, TC transport is more cost-effective and is the only viable choice at temperatures above ∼700° C. The TC system based on the carbon-dioxide reforming of methane has the best performance and lowest costs at temperatures >400°C and appears closest to meeting the DOE Solar Thermal Technology (STT) Program long-term IPH goal of 3¢/kWhth (9$/MBtuth) LEC.

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