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: A review of the state of the art with respect to RAFT alcoholic dispersion polymerization processes that proceed with polymerization-induced self-assembly (PISA) can be found in this article.
127 citations
TL;DR: It is demonstrated that paclitaxel-polymersomes have desirable restrained release profile and exhibit long-term stability and in vitro cytotoxicity showed that the ability of paclitxel-loaded polymersomes to inhibit proliferation of MCF-7 human breast cancer cells was less compared to pac litaxel alone.
Abstract: In this work, self-assembled poly(butadiene)-b-poly(ethylene oxide) (PB-PEO) polymersomes (polymer vesicles) and worm micelles were evaluated as paclitaxel carriers. Paclitaxel was successfully incorporated into PB-PEO polymersomes and worm micelles. The loading capacity of paclitaxel inside PB-PEO colloids ranged from 6.7% to 13.7% w/w, depending on the morphology of copolymer colloids and the molecular weight of diblock copolymer. Paclitaxel loaded OB4 (PB219-PEO121) polymersome formulations were colloidally stable for 4 months at 4 degrees C and exhibited slow steady release of paclitaxel over a 5 week period at 37 degrees C. Evaluation of the in vitro cytotoxicity of paclitaxel-polymersome formulations showed that the ability of paclitaxel-loaded polymersomes to inhibit proliferation of MCF-7 human breast cancer cells was less compared to paclitaxel alone. By increasing the concentration of paclitaxel in polymersomes from 0.02 to 0.2 mug/mL, paclitaxel-polymersome formulations showed comparable activity in inhibiting the growth of MCF-7 cells. Taken together, these results demonstrate that paclitaxel-polymersomes have desirable restrained release profile and exhibit long-term stability.
117 citations
TL;DR: Spherical micelles and spherical vesicles have been extensively studied as carriers of hydrophobic drugs, but highly elongated polymer-based worm micells might also serve the same purpose if release mechanisms are integrated.
116 citations
TL;DR: Fluorescence imaging shows worms are predominantly in one of two states - either entirely flexible with dynamic thermal undulations or fully rigid; only a few worms appear rigid at room temperature, indicating suppression of crystallization by both curvature and PCL hydration.
Abstract: Crystallization processes are in general sensitive to detailed conditions, but the present understanding of underlying mechanisms is insufficient. A crystallizable chain within a diblock copolymer assembly, for example, is expected to couple curvature to crystallization and thereby impact rigidity as well as preferred morphology, and yet the effects on dispersed phases have remained unclear. The hydrophobic polymer polycaprolactone (PCL) is semicrystalline in bulk (Tm = 60 °C) and is shown here to generate flexible worm micelles or rigid vesicles in water from several dozen poly(ethylene oxide)-based diblocks (PEO−PCL). Despite the fact that “worms” have a mean curvature between that of vesicles and spherical micelles, “worms” are seen only within a narrow, process-dependent wedge of morphological phase space that is deep within the vesicle phase. Fluorescence imaging shows worms are predominantly in one of two states − either entirely flexible with dynamic thermal undulations or fully rigid; only a few w...
114 citations
111 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.
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