Polymeric worm micelles as nano-carriers for drug delivery.
TL;DR: W worm micelles as blends of degradable polylactic acid and inert block copolymer amphiphiles were prepared for controlled release and initial study of carrier transport through nano-porous media, suggesting a new class of hydrophobic drug nano-carriers that are capable of tissue permeation as well as controlled release.
Abstract: Nanoscale carriers of active compounds, especially drugs, need not be spherical in shape. Worm micelles as blends of degradable polylactic acid (PLA) and inert block copolymer amphiphiles were prepared for controlled release and initial study of carrier transport through nano-porous media. The loading capacity of a typical hydrophobic drug, Triamterene, and the release of hydrophobic dyes were evaluated together with morphological changes of the micelles. Degradation of PLA by hydrolysis led to the self-shortening of worms and a clear transition towards spherical micelles, correlating with the release of hydrophobic dyes. Perhaps equally important for application is the flexibility of worm micelles, which we show allows them to penetrate nanoporous gels where 100 nm sized vesicles cannot enter. Such gels have served as tissue models, and so the results here collectively suggest a new class of hydrophobic drug nano-carriers that are capable of tissue permeation as well as controlled release.
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19 Dec 2014
1 citations
01 Jan 2015
TL;DR: This chapter illustrates various magnificent properties of individual inorganic nanoparticles and explains broadly how those properties may be utilized for successful lung cancer therapy apart from just being used as delivery systems.
Abstract: Synthetically designed inorganic nanoparticles exhibit few striking intrinsic properties which enhance their therapeutic value over the natural and synthetic organic nanoparticles. In the previous chapters, various nanoparticles as discussed were mainly used as delivery shuttles for the delivery of macromolecules at the target locations. Undoubtedly, natural and organic nanoparticles are highly biocompatible, yet they fail to circumvent the growing mortality rate of lung cancer. Hence, inorganic nanoparticles if properly designed may improve lung cancer therapy in many ways. This chapter illustrates various magnificent properties of individual inorganic nanoparticles and explains broadly how those properties may be utilized for successful lung cancer therapy apart from just being used as delivery systems.
1 citations
TL;DR: This study aims to investigate the more fundamental cell—block copolymer interaction for use in protective nanofilms to prevent biofouling of non-tissue-based implantable devices and to design durable implant—tissue interfaces that can react to various external stimuli.
Abstract: Amphiphilic block copolymers are finding increased potential in biological and medical research due to their innate alternating hydrophilic and hydrophobic blocks/segments that can be used to packa...
1 citations
Dissertation•
01 Jan 2009
TL;DR: This project sought to identify the polymer characteristics which promote drug absorption in quaternary ammonium palmitoyl glycol chitosan based nanoparticles and identified three mechanisms of oral absorption enhancement by these polymers which are increasing the solubility in the gastrointestinal fluid and improving drug permeability across the gut membrane.
Abstract: Poor physiochemical properties which lead to sub-optimal absorption and pharmacokinetic profiles have been estimated to be responsible for 40% of drug development failures. There is evidence that quaternary ammonium palmitoyl glycol chitosan (GCPQ) based nanoparticles enable the transport o f hydrophobic drugs across biological barriers and improve bioavailability. The current project was aimed at identifying the mechanism of action of these bioavailability enhancing carbohydrate nanoparticles. Our working hypothesis states that the polymers increase drug solubility in the gastrointestinal fluid and improve drug permeability across the gut membrane and we sought to identify the polymer characteristics which promote drug absorption. Six amphiphilic glycol chitosan based polymers were synthesized. The quatemised polymers formed isotropic micellar liquids whereas the non quatemised polymers formed dense nanoparticles. These polymers possess very low CAC values (3-lOOpM) thus making them stable drug delivery systems which do not fall apart upon dilution in large volumes of biological fluids like the blood and the gastrointestinal fluids. The quaternary ammonium function in the chitosan amphiphiles directed the formation of highly stable micellar aggregates (100-500nm) with enhanced drug loading ability. Both the quatemised and non quatemised polymers enhanced the oral absorption of cyclosporine and griseofulvin in rats. The area under the plasma level versus time curve was increased up to six fold when the hydrophobic dmg was administered with these polymers. The three mechanisms of oral absorption enhancement by these polymers are, a) by increasing the solubility o f hydrophobic dmgs, b) by increasing dmg residence time at the absorptive membrane of the gut via mucoadhesion, and c) by promoting transcellular uptake of hydrophobic molecules.
1 citations
01 Jan 2013
TL;DR: This study presents a simple viscoelastic model in which Lamin-A,C and -B are responsible for nuclear viscosity and elasticity, respectively, and focuses on cell nuclear physics in the context of cell migration and tumor progression as a physiological example.
Abstract: Key questions in this study are how to shrink tumors in vivo and what physical property of cancer cell determines tumor invasiveness. Delivery of drug molecules to distant tumor tissue in the body is the highest challenge in any types of cancer therapies, and this goal was approached from two aspects in the first half of the study, namely using worm-like shaped drug delivery vehicle or Filomicelle and adding protein CD47 to the vehicle surface, which can send a stop signal to macrophage phagocytosing a foreign material. Drug-loaded Filomicelles applied for brain tumor treatment in combination with radiation therapy to obtain the access inside brain tissue by disrupting blood brain barrier. CD47-attached particle was tested for accumulation in tumor tissue, followed by subcutaneous tumor shrinkage study. Second half of the study focuses on cell nuclear physics in the context of cell migration and tumor progression as a physiological example where cell migration plays an essential role for progression. Nuclear stiffness was controlled by changing the expression of Lamin-A,C, a protein forming mesh struture underneath inner nuclear membrane to give a physical strength the nucleus. Relative expression of Lamin-A,C to its isoform Lamin-B nicely predicts behavior of nuclear shape after stress application and importantly cell migration sensitivity against Lamin-A,C change through physically constraining environment. This observation leads to quite simple viscoelastic model in which Lamin-A,C and -B are responsible for nuclear viscosity and elasticity, respectively. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Chemical and Biomolecular Engineering First Advisor Dennis E. Discher
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TL;DR: The utility of polymeric micelles formed through the multimolecular assembly of block copolymers as novel core-shell typed colloidal carriers for drug and gene targeting and their feasibility as non-viral gene vectors is highlighted.
3,457 citations
TL;DR: This review examines the chemical nature of polymeric micelles as well as the methods used to characterize them with regard to drug delivery and potential medical applications, especially in cancer chemotherapy, are described and discussed.
1,200 citations
TL;DR: Experiments with poly(1,2-butadiene-b-ethylene oxide) diblock copolymers are described, which form Y-junctions and three-dimensional networks in water at weight fractions of PEO intermediate to those associated with vesicle and wormlike micelle morphologies.
Abstract: Amphiphilic compounds such as lipids and surfactants are fundamental building blocks of soft matter. We describe experiments with poly(1,2-butadiene-b-ethylene oxide) (PB-PEO) diblock copolymers, which form Y-junctions and three-dimensional networks in water at weight fractions of PEOintermediate to those associated with vesicle and wormlike micelle morphologies. Fragmentation of the network produces a nonergodic array of complex reticulated particles that have been imaged by cryogenic transmission electron microscopy. Data obtained with two sets of PB-PEOcompounds indicate that this type of self-assembly appears above a critical molecular weight. These block copolymers represent versatile amphiphiles, mimicking certain low molecular weight three-component (surfactant/water/oil) microemulsions, without addition of a separate hydrophobe.
1,126 citations
TL;DR: With all compositions, in both 100 nm and giant vesicles, the average release time reflects a highly quantized process in which any given vesicle is either intact and retains its encapsulant, or is porated and slowly disintegrates.
638 citations
TL;DR: A low molecular weight poly(ethyleneoxide)-poly(butadiene) (PEO-PB) diblock copolymer containing 50 weight percent PEO forms gigantic wormlike micelles at low concentrations (<5 percent by weight) in water.
Abstract: A low molecular weight poly(ethyleneoxide)-poly(butadiene) (PEO-PB) diblock copolymer containing 50 weight percent PEO forms gigantic wormlike micelles at low concentrations (<5 percent by weight) in water. Subsequent generation of free radicals with a conventional water-based redox reaction leads to chemical cross-linking of the PB cores without disruption of the cylindrical morphology, as evidenced by cryotransmission electron microscopy and small-angle neutron scattering experiments. These wormlike rubber micelles exhibit unusual viscoelastic properties in water.
626 citations