Micellar encapsulation

Another synthetic polymer that has shown promise in recent clinical trials for the micellar encapsulation of anticancer dmgs is a block copolymer of PEG and poly (aspartic acid) [PEG-Z -P(Asp)]. Doxombicin can be covalently attached to PEG-fi-P(Asp) through the free carboxylic acid groups on aspartic acid, and the block copolymer then forms micelles in solution with the hydrophobic aspartic acid and dmg block forming the core (Yokoyama et al. 1991 Kataoka et al. 1993). As typically occurs, the hydrated PEG chains significantly increased blood circulation... 

VIGNETTE VIII SEPARATION PROCESSES BASED ON MICELLAR ENCAPSULATION ... 

Rapoport, N. Combined cancer therapy by micellar-encapsulated drug and ultrasound. Int. J. Pharm. 2004, 277, 155-162. 

It is clear that the presence of bile salts in the G1 tract can alter drug ab-sorptiou iu mauy different ways. Bile salts may increase the total solubility of the drug compouud iu the GI lumen, possibly decrease the free concentration of the drug by micellar encapsulation or modulate the trausport characteristics of compouuds that are actively transported by the ileal bile acid transporter or by other transporters, such as P-gp (Ingels et al., 2002). 

Gao Z, Fain HD, Rapoport N. Controlled and targeted tumor chemotherapy by micellar-encapsulated drug and ultrasound. J Control Release 2005 102 203-222. 

Hayes, D.G., Kleiman, R. 1993. 1,3-Specific Upolysis of Lesquerella fendleri oil by immobilized and reverse-micellar encapsulated enzymes. J. Am. Oil Chem. Soc. 70, 1121-1127. 

In 2000, the first example of ELP diblock copolymers for reversible stimulus-responsive self-assembly of nanoparticles was reported and their potential use in controlled delivery and release was suggested [87]. Later, these type of diblock copolypeptides were also covalently crossUnked through disulfide bond formation after self-assembly into micellar nanoparticles. In addition, the encapsulation of l-anilinonaphthalene-8-sulfonic acid, a hydrophobic fluorescent dye that fluoresces in hydrophobic enviromnent, was used to investigate the capacity of the micelle for hydrophobic drugs [88]. Fujita et al. replaced the hydrophilic ELP block by a polyaspartic acid chain (D ). They created a set of block copolymers with varying... 

Dynamic light-scattering experiments or the analysis of some physicochemical properties have shown that finite amounts of formamide, A-methylformamide, AA-dimethyl-formamide, ethylene glycol, glycerol, acetonitrile, methanol, and 1,2 propanediol can be entrapped within the micellar core of AOT-reversed micelles [33-36], The encapsulation of formamide and A-methylformamide nanoclusters in AOT-reversed micelles involves a significant breakage of the H-bond network characterizing their structure in the pure state. Moreover, from solvation dynamics measurements it was deduced that the intramicellar formamide is nearly completely immobilized [34,35],... 

The potential influence of the dendrylation on the functional core unit includes sometimes a drastically increased molecule size as well as a steric shielding (encapsulation) and a micro-environment different and isolated from its external surroundings, eg., unimolecular micellar structures, electron-rich shells, solubilization. It is even possible to activate the core unit by both energy and electron transfer processes. In the following subsections, these design possibilities will be dealt with in more detail. 

The encapsulation of pDNA can also be accomplished with the use of a detergent dialysis procedure (12). In contrast to the PFV approach, the detergent dialysis procedure starts off with a micellar system and leads to encapsulation of pDNA in unilamellar liposomes called SPLP after detergent removal. Plasmid entrapment relies on a delicate balance between cationic lipid content and ionic strength of the solution. 

The catalytic principle of micelles as depicted in Fig. 6.2, is based on the ability to solubilize hydrophobic compounds in the miceUar interior so the micelles can act as reaction vessels on a nanometer scale, as so-called nanoreactors [14, 15]. The catalytic complex is also solubihzed in the hydrophobic part of the micellar core or even bound to it Thus, the substrate (S) and the catalyst (C) are enclosed in an appropriate environment In contrast to biphasic catalysis no transport of the organic starting material to the active catalyst species is necessary and therefore no transport limitation of the reaction wiU be observed. As a consequence, the conversion of very hydrophobic substrates in pure water is feasible and aU the advantages mentioned above, which are associated with the use of water as medium, are given. Often there is an even higher reaction rate observed in miceUar catalysis than in conventional monophasic catalytic systems because of the smaller reaction volume of the miceUar reactor and the higher reactant concentration, respectively. This enhanced reactivity of encapsulated substrates is generally described as micellar catalysis [16, 17]. Due to the similarity to enzyme catalysis, micelle and enzyme catalysis have sometimes been correlated in literature [18]. 

Meier MAR, Aerts SNH, Staal BBP, Rasa M, Schubert US (2005) PEO-h-PCL block copolymers synthesis, detailed characterization, and selected micellar drug encapsulation behavior. Macromol Rapid Commun 26 1918-1924... 

For some systems, at high concentration, inverse phases are observed. That is, one may generate an inverse hexagonal columnar phase (columns of water encapsulated by amphiphiles), or an inverse micellar phase (a bulk LC sample with spherical water cavities). 

Hemes encapsulated in aqueous detergent micelles find themselves in a large macromolecular cavity whose interaction is mainly hydrophobic. It has been suggested that such systems appear to simulate the electrostatic and hydrophobic interactions of the heme cavity in metalloproteins. The present article surveys reported studies on natural and synthetic hemes, both ferric and ferrous, incorporated inside micelles of different sizes and surface charges. The emphasis is laid on multinuclear NMR and optical spectroscopic studies. The effect of micellar interactions on the electronic properties of hemes is discussed and compared with that of the heme cavity in proteins. 

It has been suggested that aqueous micellar systems simulate the electrostatic and hydrophobic interactions of the heme cavity [15-23]. Pioneering studies by Simplicio et al. [15-17] have shown that the heme is monodispersed when encapsulated in aqueous micelles. They have studied binding of cyanide and other axial ligands to ferric hemes in micellar environments. These studies [15-23] indicated that a heme encapsulated in an aqueous detergent micelle finds itself inside a large macromolecular cavity whose interactions is primarily... 

The activation energies calculated for the two steps of the above reaction are + 160 kJ/mol for the ki step and -l- 78 kJ/mol for the k2 step [15]. The overall enthalpy of reaction is — 78 kJ/mol. It has been found that the half-life for the ki reaction is sensitive to the counterion concentration in case of SDS micelles. The effect of added counterion may be due to the charge neutralisation of the sulphate anion heads in the SDS micellar Stern layer, to facilitate approach and penetration of the CN- ions at the micelle-water interface. Hemin encapsulated in CTAB micelles reacts much faster with cyanide compared to that in SDS presumably because of the cationic Stern layer in CTAB. The... 

The dithionite reduction of the micelle encapsulated aqua (hydroxo) ferric hemes at pH 10 (in inert atmosphere) gives an iron (II) porphyrin complex whose optical spectrum [21] shows two well-defined visible bands at 524 and 567 nm and a Soret band split into four bands (Fig. 10). Such spectral features are typical of four-coordinate iron (II) porphyrins. The magnetic moment (p = 3.8 + 0.2 Pb) of this sample in the micellar solution is also typical of intermediate spin iron(II) system and is similar to that reported for four-coordinate S = 1 iron(II) porphyrins and phthalocyanine [54-56]. The large orbital-contribution (ps.o. = 2.83 p for S = 1) observed in this iron(II) porphyrin... 

The micelle-encapsulated six coordinated bis(pyridinato) iron(II) complexes of protoporphyrin and OEP have been reported by addition of pyridine to the four coordinate ferrous complex in aqueous micellar solution. The optical spectrum of [Fe(II)(PP)(Py)2] in micelle (Fig. 10) is identical to S = 0 six-coordinate bis(pyridinato) iron(II) porphyrin complex [3]. The magnetic moment measurements in solution confirm their diamagnetic nature. The HNMR spectra are also characteristic low-spin iron(II) resonances (S = 0) with shifts lying in the diamagnetic region (Table 2). 

A general observation from the HNMR studies on micelle-encapsulated heme is that the line width of the heme protons increases significantly in the micellar solutions compared to those in simple solutions. The change in linewidths of heme methyl protons in micelles is not as large in low-spin Fe(III) hemes as in the high-spin ones. The linewidths in four-coordinate and five-coordinate complexes of ferrous hemes in aqueous micellar solutions are also quite broad compared to those observed in benzene solutions [12, 61], but are similar to those of hemoproteins [2,62]. We examine below the origin and implications of the linewidth change in micellar solutions. 

Nguyen PM, Hammond PT. Amphiphilic linear-dendritic triblock copolymers composed of poly(amidoamine) and poly(propylene oxide) and their micellar-phase and encapsulation properties. Langmuir 2006 22 7825-7832. 

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