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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TL;DR: It is found that the micelle structure grows epitaxially through the addition of more polymer, producing micelles with a narrow size dispersity, in a process analogous to the growth of living polymer.
Abstract: Block copolymers consist of two or more chemically different polymers connected by covalent linkages. In solution, repulsion between the blocks leads to a variety of morphologies, which are thermodynamically driven. Polyferrocenyldimethylsilane block copolymers show an unusual propensity to forming cylindrical micelles in solution. We found that the micelle structure grows epitaxially through the addition of more polymer, producing micelles with a narrow size dispersity, in a process analogous to the growth of living polymer. By adding a different block copolymer, we could form co-micelles. We were also able to selectively functionalize different parts of the micelle. Potential applications for these materials include their use in lithographic etch resists, in redox-active templates, and as catalytically active metal nanoparticle precursors.
947 citations
TL;DR: Different approaches to fabricate polymeric nanostructures of various shapes are reviewed, a comprehensive summary on the current understandings of the influence of nanostructure with different shapes on important biological processes in drug delivery is provided, and future perspectives for the development of nanstructures with well-defined shapes for drug delivery are discussed.
Abstract: Amphiphilic polymeric nanostructures have long been well-recognized as an excellent candidate for drug delivery applications. With the recent advances in the “top-down” and “bottom-up” approaches, development of well-defined polymeric nanostructures of different shapes has been possible. Such a possibility of tailoring the shape of the nanostructures has allowed for the fabrication of model systems with chemically equivalent but topologically different carriers. With these model nanostructures, evaluation of the importance of particle shape in the context of biodistribution, cellular uptake and toxicity has become a major thrust area. Since most of the current polymeric delivery systems are based upon spherical nanostructures, understanding the implications of other shapes will allow for the development of next generation drug delivery vehicles. Herein we will review different approaches to fabricate polymeric nanostructures of various shapes, provide a comprehensive summary on the current understandings of the influence of nanostructures with different shapes on important biological processes in drug delivery, and discuss future perspectives for the development of nanostructures with well-defined shapes for drug delivery.
460 citations
TL;DR: This succinct review of the recent literature is collated to assess the current state of understanding of the influence of nanoparticle shape on the effectiveness of drug delivery with a special emphasis on cancer therapy.
Abstract: Introduction: Nanoparticles have been successfully used for cancer drug delivery since 1995. In the design of commercial nanoparticles, size and surface characteristics have been exploited to achieve efficacious delivery. However, the design of optimized drug delivery platforms for efficient delivery to disease sites with minimal off-target effects remains a major research goal. One crucial element of nanoparticle design influencing both pharmacokinetics and cell uptake is nanoparticle morphology (both size and shape). In this succinct review, the authors collate the recent literature to assess the current state of understanding of the influence of nanoparticle shape on the effectiveness of drug delivery with a special emphasis on cancer therapy.Areas covered: This review draws on studies that have focused on the role of nonspherical nanoparticles used for cancer drug delivery. In particular, the authors summarize the influence of nanoparticle shape on biocirculation, biodistribution, cellular uptake and ...
433 citations
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TL;DR: It is demonstrated that living polymerizations driven by the epitaxial crystallization of a core-forming metalloblock represent a synthetic tool that can be used to generate complex and hierarchical micelle architectures from diblock copolymers.
Abstract: Block copolymers consist of two or more chemically distinct polymer segments, or blocks, connected by a covalent link. In a selective solvent for one of the blocks, core-corona micelle structures are formed. We demonstrate that living polymerizations driven by the epitaxial crystallization of a core-forming metalloblock represent a synthetic tool that can be used to generate complex and hierarchical micelle architectures from diblock copolymers. The use of platelet micelles as initiators enables the formation of scarf-like architectures in which cylindrical micelle tassels of controlled length are grown from specific crystal faces. A similar process enables the fabrication of brushes of cylindrical micelles on a crystalline homopolymer substrate. Living polymerizations driven by heteroepitaxial growth can also be accomplished and are illustrated by the formation of tri- and pentablock and scarf architectures with cylinder-cylinder and platelet-cylinder connections, respectively, that involve different core-forming metalloblocks.
403 citations
TL;DR: Comparisons of polymersomes with viral capsids are shown to encompass and inspire many aspects of current designs, and polymersome loading, in vivo stealthiness, degradation-based disassembly for controlled release, and even tumor-shrinkage in vivo are reviewed.
Abstract: Polymersomes are self-assembled shells of amphiphilic block copolymers that are currently being developed by many groups for fundamental insights into the nature of self-assembled states as well as for a variety of potential applications. While recent reviews have highlighted distinctive properties - particularly stability - that are strongly influenced by both copolymer type and polymer molecular weight, here we first review some of the more recent developments in computational molecular dynamics (MD) schemes that lend insight into assembly. We then review polymersome loading, in vivo stealthiness, degradation-based disassembly for controlled release, and even tumor-shrinkage in vivo. Comparisons of polymersomes with viral capsids are shown to encompass and inspire many aspects of current designs.
367 citations
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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.
Abstract: Recently, colloidal carrier systems have been receiving much attention in the field of drug targeting because of their high loading capacity for drugs as well as their unique disposition characteristics in the body. This paper highlights 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. The process of micellization in aqueous milieu is described in detail based on differences in the driving force of core segregation, including hydrophobic interaction, electrostatic interaction, metal complexation, and hydrogen bonding of constituent block copolymers. The segregated core embedded in the hydrophilic palisade is shown to function as a reservoir for genes, enzymes, and a variety of drugs with diverse characteristics. Functionalization of the outer surface of the polymeric micelle to modify its physicochemical and biological properties is reviewed from the standpoint of designing micellar carrier systems for receptor-mediated drug delivery. Further, the distribution of polymeric micelles is described to demonstrate their long-circulating characteristics and significant tumor accumulation, emphasizing their promising utility in tumor-targeting therapy. As an important perspective on carrier systems based on polymeric micelles, their feasibility as non-viral gene vectors is also summarized in this review article.
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.
Abstract: Polymeric micelles have recently emerged as a novel promising colloidal carrier for the targeting of poorly water soluble and amphiphilic drugs. Polymeric micelles are considerably more stable than surfactant micelles and can solubilize substantial amounts of hydrophobic compounds in their inner core. Due to their hydrophilic shell and small size they sometimes exhibit prolonged circulation times in vivo and can accumulate in tumoral tissues. This review examines the chemical nature of polymeric micelles as well as the methods used to characterize them with regard to drug delivery. Special emphasis is put on the determination of critical micelle concentration and on drug loading procedures. 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.
Abstract: Controlled release polymer vesicles are prepared using hydrolysable diblock copolymers of polyethyleneglycol-poly-l-lactic acid (PEG-PLA) or polyethyleneglycol-polycaprolactone (PEG-PCL). Encapsulation studies with a common anti-cancer agent, doxorubicin, show loading comparable to liposomes. Rates of encapsulant release from the hydrolysable vesicles are accelerated with an increased proportion of PEG but are delayed with a more hydrophobic chain chemistry (i.e. PCL). Rates of release also rise linearly with the molar ratio of degradable copolymer blended into membranes of a non-degradable, PEG-based block copolymer (PEG-polybutadiene (PBD)). With all compositions, in both 100 nm and giant vesicles, the average release time (from hours to days) reflects a highly quantized process in which any given vesicle is either intact and retains its encapsulant, or is porated and slowly disintegrates. Poration occurs as the hydrophobic PLA or PCL block is hydrolytically scissioned, progressively generating an increasing number of pore-preferring copolymers in the membrane. Kinetics of this evolving detergent mechanism overlay the phase behavior of amphiphiles with transitions from membranes to micelles allowing controlled release.
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