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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Dissertation•
06 Aug 2007
TL;DR: This dissertation focuses on the formation and dynamics of reverse structures, and describes a new route for forming reverse wormlike micelles in nonpolar organic liquids using bile salt to solutions of the phospholipid, lecithin.
Abstract: Title of Document: SELF-ASSEMBLY OF AMPHIPHILIC MOLECULES IN ORGANIC LIQUIDS Shih-Huang Tung, Doctor of Philosophy, 2007 Directed By: Professor Srinivasa R. Raghavan, Department of Chemical and Biomolecular Engineering Amphiphilic molecules are well-known for their ability to self-assemble in water to form structures such as micelles and vesicles. In comparison, much less is known about amphiphilic self-assembly in nonpolar organic liquids. Such “reverse” self-assembly can produce many of the counterparts to structures found in water. In this dissertation, we focus on the formation and dynamics of such reverse structures. We seek to obtain fundamental insight into the driving forces for reverse self-assembly processes. Three specific types of reverse structures are studied: (a) reverse wormlike micelles, i.e., long, flexible micellar chains; (b) reverse vesicles, i.e., hollow containers enclosed by reverse bilayers; and (c) organogel networks. While our focus is on the fundamentals, we note that reverse structures can be useful in a variety of applications ranging from drug delivery, controlled release, hosts for enzymatic reactions, and templates for nanomaterials synthesis. In the first part of this study, we describe a new route for forming reverse wormlike micelles in nonpolar organic liquids. This route involves the addition of trace amounts of a bile salt to solutions of the phospholipid, lecithin. We show that bile salts, due to their unique “facially amphiphilic” structure, can promote the aggregation of lecithin molecules into these reverse micellar chains. The resulting samples are viscoelastic and show interesting rheological properties. Unusual trends are seen in the temperature dependence of their rheology, which indicates the importance of hydrogenbonding interactions in the formation of these micelles. Another remarkable feature of their rheology is the presence of strain-stiffening, where the material becomes stiffer at high deformations. Strain-stiffening has been seen before for elastic gels of biopolymers; here, we demonstrate the same properties for viscoelastic micellar solutions. The second reverse aggregate we deal with is the reverse vesicle. We present a new route for forming stable unilamellar reverse vesicles, and this involves mixing shortand long-chain lipids (lecithins) with a trace of sodium chloride. The ratio of the short to long-chain lipid controls the type and size of self-assembled structure formed, and as this ratio is increased, a transition from reverse micelles to vesicles occurs. The structural changes can be explained in terms of molecular geometry, with the sodium chloride acting as a “glue” in binding lipid headgroups together through electrostatic interactions. The final part of this dissertation focuses on organogels. The two-tailed anionic surfactant, AOT, is well-known to form spherical reverse micelles in organic solvents. We have found that trace amounts (e.g., less than 1 mM) of the dihydroxy bile salt, sodium deoxycholate (SDC) can transform these dilute micellar solutions into selfsupporting, transparent organogels. The structure and rheology of these organogels is reminiscent of the self-assembled networks formed by proteins such as actin in water. The organogels are based on networks of long, rigid, cylindrical filaments, with SDC molecules stacked together in the filament core. SELF-ASSEMBLY OF AMPHIPHILIC MOLECULES IN ORGANIC LIQUIDS
2 citations
Cites background from "Polymeric worm micelles as nano-car..."
...In fact, wormlike micelles have been shown to be capable of tissue permeation and controlled release.(111)...
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TL;DR: The hydrophobic chain structure and length were shown to strongly affect the relative stabilities of these phases, allowing the self-assembled structure to be varied at will.
Abstract: The phase behavior and self-assembly structures of a series of amphiphilic diblock co-oligomers comprising an ionizable hydrophilic block (5 to 10 units of acrylic acid) and a hydrophobic block (5 to 20 units of n-butyl acrylate, t-butyl acrylate, or ethyl acrylate), synthesized by RAFT polymerization, have been examined by polarizing optical microscopy and small-angle X-ray scattering (SAXS). Self-assembled structure and lyotropic phase stability in these systems is highly responsive to the degree of ionization of the acrylic acid hydrophilic block (i.e., pH), concentration, and nature of the hydrophobic block. Increasing headgroup ionization switched the amphiphiles from behaving like soluble to insoluble surfactants. Liquid isotropic (micellar), hexagonal, lamellar, and discrete cubic phases were found under different solution conditions. The surfactant packing parameter was adapted to understand the self-assembly structures in these diblock co-oligomers. The hydrophobic chain structure and length were...
2 citations
TL;DR: In this paper, the shape of polymeric nanostructures represents a key to required tissue selectivity in the intestine, and the authors demonstrate an untapped potential in particle design and enable new vistas for an effective treatment of inflammatory bowel disease.
Abstract: Over the 21st century, inflammatory bowel disease (IBD) has become a global disease with no causal therapeutic options. Selective targeting of inflamed areas in the gastrointestinal tract could be an effective treatment circumventing severe side effects for healthy tissue. Our study demonstrates that the shape of polymeric nanostructures represents so far rarely addressed key to required tissue selectivity in the intestine. Ex vivo experiments on human colonic biopsies revealed that crosslinked wormlike micelles featuring a dense poly(ethylene oxide) (PEO) shell exclusively enter the inflamed human mucosa without affecting healthy tissue. Similarly designed spherical micelles (∼25 nm) or vesicles (∼120 nm) penetrate both tissues or were barely uptaken at all, respectively. Moreover, it was found that the particles colocalize with immune cells in the lamina propria facilitating a specific targeting of the main pro-inflammatory cells within the diseased human mucosa. These findings demonstrate an untapped potential in particle design and enable new vistas for an effective treatment of IBD.
2 citations
TL;DR: The molecular surface analysis of the modeled CNNs along with molecular dynamic simulations studies toward revealing the noninvasive cellular internalization potential of these CNNs and a case study has been carried to study the ability of CNNs to translocate silver nanoparticles across membrane.
Abstract: We explore with molecular modeling, dynamics simulations, and a statistical model the ability of chitosan nanoneedles (CNNs) to be internalized into a model lipid bilayer as a function of their length, keeping in view of their applications in the field of biomedicine for advanced targeted drug delivery. In this study, we have computationally modeled and studied the structural geometry and the stability of CNNs formed by 4, 6, and 8 subunits. We reported the molecular surface analysis of the modeled CNNs along with molecular dynamic (MD) simulations studies toward revealing the noninvasive cellular internalization potential of these CNNs and a case study has been carried to study the ability of CNNs to translocate silver nanoparticles across membrane. The present results are strongly in support of further exploration of 8 subunits based CNNs for their application as target drug delivery vehicles. The hydrophilicity of the CNNs has been attributed as one of the key factors responsible for the internalizatio...
2 citations
Cites background from "Polymeric worm micelles as nano-car..."
...Among them, CNNs are foreseen as potential candidates for drug and therapeutic peptides delivery (Bergemann et al., 1999; Gallo et al., 2007; Kim et al., 2005; Simon et al., 2007; Vinogradov, Bronich, & Kabanov, 2002)....
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References
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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