Worm micelles

Kim Y, Dalhaimer P et al (2005) Polymeric worm micelles as nano-carriers for thug delivery. Nanotechnology 16 S484... 

Dalhaimer P, Bates FS et al (2003) Single molecule visualization of stable, stiffness-tunable, flow-conforming worm micelles. Macromolecules 36 6873-6877... 

Kim, Y Dalhaimer, R Christian, D. A. Discher, D. E. Rolymeric worm micelles as nano-carriers for drug delivery. Nanotechnology 2005, 16, 484 91. 

The hydrophobic core of worm-like micelles may be further related to the molecular weight of the copolymers hydrophobic block. A fully stretched block of N/ monomer units would theoretically assemble into an object with diameter, d Np,, and blocks of ideal random coils would have d The strong segregation limit (SSL) theory predicts that strong segregation balances the interfacial tension against the chain elasticity and that the core diameter, d, of the worm micelles would scale with ZVai of the hydrophobic block at ... 

Delgado, J. Castillo, R. (2007). Shear-induced structures formed during thixotropic loops in dilute worm-micelle solutions, /. Coll. Int. Sci. 312 481. 

Degradable Poly(ethylene oxide)-block-Polycaprolactone Worm Micelles... 

Preparation of OCL Worm Micelles by Cosolvent/evaporation Method... 

Olympus 1X71 inverted fluorescence microscope with a 60X objective and a Cascade CCD camera was used to visualize OCL worm micelles. A hydrophobic fluorophore dye (PKH 26) was added to the OCL worm micelles, and 2 pL sample was used in the glass slide-cover slip chamber and approximately 20 pictures were taken per sample. Analysis detail was described elsewhere (2S). Cryo-TEM was also used to visualize OCL worm micelle morphological change. Sample preparation and analysis was described elsewhere. 14)... 

Gel Permeation Chromatography (GPC) Studies on OCL Worm Micelle Degradation... 

Fresh whole blood was pelleted by centrifugation and 100 pi of the collected red blood cell (RBC) suspension was added to 900 pi of 10 mg/ml OCL worm micelles in PBS (RBC 10% hematocrit in PBS). The samples were incubated for 24 hours at 37°C. The release of hemoglobin in the supernatant, collected by centrifugation, was measured by UV-Vis at 412 nm and compared to the complete hemolysis by 0.2% small surfactants Triton X-100. 

Stock solutions of taxol in methanol (5mg/ml) was added with a weight ratio of 0.2 1 to 1 ml of OCL worm micellar solutions at different concentrations and vortexed for 5 minutes. The small amount of methanol was removed by dialysis at 4 °C for 2 hours. Unloaded taxol precipitate was centrifuged down at 3000 rpm for 5 min and further removed from the micelle supernatant by filtering with a 0.45 pm pore-sized syringe filter. The amount of taxol loaded into OCL worm micelles was then determined by HPLC. A Waters Breeze HPLC equipped with a diode array UV detector set at A, = 220 nm, connected with a Symmetry C-18 column, methanol as the mobile phase, and a flow rate of 0.8 mL/min was used. Taxol is well resolved from OCL peak, and the amount of taxol was estimated from its calibration curve that correlates peak area with amount. 

As OCL worm micelles shorten to spherical micelles with time, the PCL hydrolysis monomer product, 6-hydroxycaproic acid (6-HPA), was found by GPC as the predominant new species generated. Figure 2. 6-HPA peak is well resolved from dimer, trimer, and larger caprolactone oligomers, and no other significant degradation products were detected, Figure2b. The polydispersity of... 

Figure L Self-assembled OCL worm micelles spontaneously shorten to spherical miceller. a. Visualized by FM and cryo-TEM(inset,bar=100nm) b. Dynamic snapshots of single OCL worm micelle c. Contour length distributions. (Reproduced from reference 16. Copyright 2005 ACS)...

Figure 2. a. GPC chromatograms of OCLl worm micelle at different degradation times, at 37 1C. b. Identification of monomer 6-HPA with standards. (Reproducedfrom reference 16. Copyright 2005 ACS)... 

OCL copolymer remained essentially the same, Figure 2a, and the loss of caprolactone units from OCL copolymer was further confirmed by NMR, Figure 3. Quantitative accumulation of 6-HPA, Figure 4a, parallels both in form and time-scales of the decays in mean contour length of OCL worm micelles for both copolymers, Figure 4b. The analytical results thus demonstrate that PCL in... 

While the end-cleavage of PCL within worm micelles appears consistent with both the chemical and the nano-scale physical changes, it is also considerably faster than the slow hydrolysis reported for PCL homo/copolymer bulk, particle, or films, i.e. on the time scale of months-years under the same condition. (2-5) The distinction arises with the specific effect of OCL worm micelles on PCL hydrolysis. As speculated from studies on spherical micelles (27), the terminal -OH of the hydrophobic PCL block is not strictly sequestered in the dry , hydrophobic core but tends to be drawn into the hydrated corona. A micellar catalysis effect involving interfacial water (28) plus the likely... 

For both OCLl and OCL3 worm micelles, shortening rate constants measured from FM increase exponentially with temperature, with minimal degradation at 4°C but considerable hydrolysis at the physiological temperature of 37 C. The temperature dependences fit classic Arrhenius behavior and yield activation energies a for the morphological transformations. Figure 6. 

Evaluation of Degradable OCL Worm Micelles for Drug Delivery... 

Bovine aortic endothelial cells and vascular smooth muscle cells exposed to OCL worm micelles in PBS with a dose of S mg/ml showed no ill-effects for up to 5 days. OCL worm micelles and their degradation product, 6-hydroxycaproic acid are non-toxic and compatible with cultured cells. Incubating OCL worm micelles with whole blood for two days at 37°C shows that they don t stick to red blood cells (RBC) and remains suspended in plasma and retains their flexibility. Also, hemolysis study on OCL worm micelles (lOmg/ml) shows negligible hemolytic activity (< 1%). (27)... 

The current clinical formulation of anti-cancer drug taxol is in a 50 50 mixture of Cremophore EL and ethanol, which is physically incompatible with intravenous infusion system and causes serious side effects such as hypersensitivity and neurotoxicity. (31) Here, degradable OCL worm micelles prove to be compatible with cultured cells and blood, offering great advantage over the conventionally surfactants as a potential alternative carrier for taxol. 

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