micelles
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Konduktometricky bol študovaný vplyv teploty na kritickú micelovú koncentráciu a termodynamické parametre micelizácie šiestich hydrochloridových solí lokálnych anestetík - prokaín (I), trimekaín (II), cinchokaín (III), tetrakaín (IV), pentakaín (V) a heptakaín (VI). V intervale teplot 15 až 45 °C boli namerané závislosti mernej vodivosti od koncentrácie, na ktorých boli pozorované dva výrazné zlomy zodpovedajúce atómom dusíka v skelete molekúl študovaných látok.
The effect of temperature on the critical micellar concentration and thermodynamic parameters of micelles formation of six hydrochloride salts of local anesthetics - procaine (I), trimecaine (II), cinchocaine (III), tetracaine (IV), pentacaine (V) and heptacaine (VI) - was studied by using conductometry. At the temperature interval from 15 to 45°C, the dependencies of the measured conductivity versus concentration of the studied compounds showed two explicit breaks in the direction related to the presence of nitrogen atom in the skeleton of these compounds.
Coordination of lipophilic alkyl pyridin-2-yl ketoximes 1 to Ni2+ ions, reduction of lipophilic 3-alkoxyacetophenones 2 with sodium borohydride, and alkaline hydrolysis of 4-nitrophenyl diphenyl phosphate (PNPDPP) were employed as probes in the investigation which factors may influence the reactivity of organic compounds in micellar systems. In all these reactions, a lipophilic substrate solubilized in micellar core was attacked by a hydrophilic reagent from the bulk aqueous phase. To evaluate the contribution of electrostatic interactions between the micellar surface charge and the reagent to the observed reactivity, we combined reactions involving the reagents with opposite polarity (Ni2+ cations and borohydride or hydroxide anions) with positively charged micelles of hexadecyltrimethylammonium chloride (CTAC) or bromide (CTAB) and negatively charged micelles of sodium dodecyl sulfate (SDS). Non-ionic micelles (Triton X-100 or Brij 35) served as a reference. The results of the kinetic studies give evidence that each of the investigated systems has unique properties going in particular aspects beyond the scope of the generally accepted concepts of reactivity in micelles.
The values of CMC (critical micellar concentration) for buffered surfactant solutions used in separation methods in analytical chemistry, especially in micellar electrokinetic capillary chromatography, were studied by conductivity, surface tension and viscosity measurements. The study involved solutions of representative anionic (SDS), cationic (CTAB), and non-ionic (TX100, GX080) surfactants. The data measured for aqueous solutions were in good agreement with the published data. The data for buffer solutions confirmed theoretical presumptions ? the CMC values decreased with increasing ionic strength of the solutions. In contrast, viscoelastic properties of the solutions of surfactants were not significantly influenced by the ionic strength or pH of the solutions.
Thermoresponsive polymer micelles are promising drug and radionuclide carriers with a strong passive targeting effect into solid tumors. We have synthesized ABA triblock copolymers poly[2-methyl-2-oxazoline-block-(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazoline)-block-2-methyl-2-oxazoline]. These polymers are molecularly dissolved in aqueous millieu below the cloud point temperature (CPT) of the thermoresponsive central block and above CPT form polymer micelles at CMC 5-10 × 10(-5) g · mL(-1) with diameter ≈200 nm. The phenolic moiety introduced into the copolymer allowed radionuclide labeling with iodine-125 ongoing in good yield with sufficient in vitro stability under model conditions.
The structural formula of biologically important chiral pigments bilirubin and biliverdin differs only by one double bond. We showed that this results in dissimilar interactions with two models of membranes: cationic liposomes composed of 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol and zwitterionic micelles from 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). While the liposomes recognized the P-form of bilirubin, the micelles recognized its M-form. Both recognized the P-form of biliverdin. Our study also comprised ternary systems consisting of the pigments, model membranes and serum albumin (human and bovine). Bilirubin preferentially interacted with the albumins even in the presence of the liposomes. On the other hand, biliverdin preferred the liposomes. Remarkably, the presence of CHAPS completely changed the biliverdin binding to the protein. Because our study was oriented on different chiral interactions, a chiroptical method of electronic circular dichroism was chosen as the principal method to study our systems. As complementary methods, UV-vis absorption and fluorescence emission were used.
- MeSH
- biliverdin chemie metabolismus MeSH
- cholesterol analogy a deriváty metabolismus MeSH
- kompetitivní vazba MeSH
- kyseliny cholové metabolismus MeSH
- lidé MeSH
- micely * MeSH
- molekulární konformace MeSH
- molekulární modely MeSH
- sérový albumin hovězí metabolismus MeSH
- skot MeSH
- stereoizomerie MeSH
- unilamelární lipozómy chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Physical and chemical structure of paclitaxel (PTX) was studied after its incorporation into polymeric micelles made of hyaluronic acid (HA) (Mw=15 kDa) grafted with C6 or C18:1 acyl chains. PTX was physically incorporated into the micellar core by solvent evaporation technique. Maximum loading capacity for HAC6 and HAC18:1 was determined to be 2 and 14 wt.%, respectively. The loading efficiency was higher for HAC18:1 and reached 70%. Independently of the derivative, loaded HA micelles had spherical size of approximately 60-80 nm and demonstrated slow and sustained release of PTX in vitro. PTX largely changed its form from crystalline to amorphous after its incorporation into the micelle's interior. This transformation increased PTX sensitivity towards stressing conditions, mainly to UV light exposure, during which the structure of amorphous PTX isomerized and formed C3C11 bond within its structure. In vitro cytotoxicity assay revealed that polymeric micelles loaded with PTX isomer had higher cytotoxic effect to normal human dermal fibroblasts (NHDF) and human colon carcinoma cells (HCT-116) than the same micelles loaded with non-isomerized PTX. Further observation indicated that PTX isomer influenced in different ways cell morphology and markers of cell cycle. Taken together, PTX isomer loaded in nanocarrier systems may have improved anticancer activity in vivo than pure PTX.
- MeSH
- fibroblasty účinky léků MeSH
- fytogenní protinádorové látky aplikace a dávkování chemie MeSH
- HCT116 buňky MeSH
- hydrofobní a hydrofilní interakce MeSH
- isomerie MeSH
- kultivované buňky MeSH
- kyselina hyaluronová aplikace a dávkování chemie MeSH
- lidé MeSH
- micely * MeSH
- nosiče léků aplikace a dávkování chemie MeSH
- paclitaxel aplikace a dávkování chemie MeSH
- polymery aplikace a dávkování chemie MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Polymeric micelles are attractive drug delivery systems for intravenously administered nonpolar drugs. Although physical parameters like size, shape and loading capacity are considered as the most important for their efficiency, here we demonstrate that the effects of serum protein interaction and characteristics of loaded compound cannot be neglected during the micelle development and design of experimental set up. Polymeric micelles prepared from amphiphilic hyaluronic acid grafted with short (hexanoic) and long fatty acids (oleic) were tested after loading with two different hydrophobic models, Nile red and curcumin. The composition of micelles affected mainly the loading capacity. Both encapsulated compounds behaved differently in the in vitro cell uptake, which was also influenced by serum concentration, where serum albumin was found to be the primary destabilizing component. This destabilization was found to be influenced by polymeric micelle concentration. Thus, the chemical structure of micelle, the properties of non-covalently loaded substance and serum albumin/polymeric micelle ratio modulate the in vitro intracellular uptake of drugs loaded in nanocarriers.
- MeSH
- buňky HT-29 MeSH
- HCT116 buňky MeSH
- intracelulární tekutina účinky léků metabolismus MeSH
- kyselina hyaluronová aplikace a dávkování metabolismus MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- micely * MeSH
- nosiče léků aplikace a dávkování metabolismus MeSH
- polymery aplikace a dávkování metabolismus MeSH
- sérový albumin aplikace a dávkování metabolismus MeSH
- vazba proteinů fyziologie MeSH
- viabilita buněk účinky léků fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
To optimally exploit the potential of (tumor-) targeted nanomedicines, platform technologies are needed in which physicochemical and pharmaceutical properties can be tailored according to specific medical needs and applications. We here systematically customized the properties of core-crosslinked polymeric micelles (CCPM). The micelles were based on mPEG-b-pHPMAmLacn(i.e. methoxy poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide-lactate]), similar to the block copolymer composition employed in CriPec® docetaxel, which is currently in phase I clinical trials. The CCPM platform was tailored with regard to size (30 to 100nm), nanocarrier degradation (1month to 1year) and drug release kinetics (10 to 90% in 1week). This was achieved by modulating the molecular weight of the block copolymer, the type and density of the crosslinking agent, and the hydrolytic sensitivity of the drug linkage, respectively. The high flexibility of CCPM facilitates the development of nanomedicinal products for specific therapeutic applications.
The main limitation of contemporary anticancer chemotherapy remains to be the insufficient specificity of the drugs for tumor tissue, which decreases the maximum tolerated dose due to severe side effects. Micellar drug delivery systems based on amphiphilic block copolymers with a very narrow size distribution (10 to 100 nm in diameter) is a novel innovative approach. Here, we report biological and pharmacological properties of polymeric micellar conjugate containing doxorubicin (DOX) covalently bound via hydrolytically cleavable hydrazone bonds to the micelle core. The system had a very low systemic toxicity (almost 20 times lower than free DOX) and long circulation in the bloodstream (with half of the dose after 24 h). Significant accumulation of tested micelles within the tumor was confirmed by fluorescent whole body imaging. Our new micellar system showed promising therapeutic activity against established murine EL-4 T-cell lymphoma; it was found that it is able to completely cure about 75% of tumor-bearing mice (with doses of either 1 x 150 mg DOX kg(-1) or 2 x 75 mg DOX kg(-1), administered i.v.). Moreover, treatment with micelles in cured mice induced tumor-specific resistance. Up to 80% of these mice survived rechallenge with original but not with distinct tumor cells.
- MeSH
- doxorubicin aplikace a dávkování farmakokinetika MeSH
- hydrazony MeSH
- hydrolýza MeSH
- indukce remise MeSH
- lékové transportní systémy metody MeSH
- lymfom T-buněčný farmakoterapie MeSH
- micely MeSH
- myši MeSH
- nanočástice chemie MeSH
- poločas MeSH
- polymery farmakokinetika chemie terapeutické užití MeSH
- protinádorové látky aplikace a dávkování farmakokinetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
