Drug-loading micelles

Crison et al. [52] presented an alternative derivation of Eq. (29) that included individualized transport of the solute and micelle while still maintaining the basic assumption of equilibrium. This was accomplished by rewriting Eq. (24) to include the magnitude of the individual diffiisional boundary layers for free drug and drug-loaded micelle according to Eq. (10), as follows ... 

The reaction plane model with heterogeneous reactions was discussed at length for acid-base reactions in the previous section. The same modeling technique, of confining the reactions to planes, can be applied to micelle-facilitated dissolution. As with the acid-base model, one starts with a one-dimensional steady-state equation for mass transfer that includes diffusion, convection, and reaction. This equation is then applied to the individual species i, i.e., the solute, s, the micelle, m, and the drug-loaded micelle, sm, to yield... 

The solid dispersion method (Fig. 2B) was used for solubilization of paclitaxel into PEG-poly(D,L-lactide) diblock copolymer micelles. Paclitaxel and the polymer were dissolved in acetonitrile followed by evaporation of the solvent under a stream of nitrogen at 60°C to obtain a gel-like polymer-drug matrix. Dissolution of the solid matrix in water at about 60° C with stirring led to formation of drug-loaded micelles. Because a heating is needed to completely dissolve the polymer-drug matrix, this method may not be not desirable for thermally unstable drugs. 

Fig. 2 A first generation of drug-loading micelles, a Schematic illustration of the formation of polymeric micelle of Dox-conjugated PEG-PAsp block copolymer. Additional Dox can be physically entrapped in the micelle, b Chemical structures of PEG-PAsp block copolymer and Dox...

Fig. 4 A second generation of the drug loading micelle with a pH-sensitive drug releasing property, a Formation of pH-sensitive polymeric micelles from PEG-(PAsp-Hyd-Dox) block copolymers. Antitumor drugs (Dox), conjugated through acid-labile hydrazone linkers, are released in lower pH conditions, b Time- and pH-dependent Dox release profile from the micelles. The micelles selectively release Dox under the pH condition of region B, which corresponds to the intracellular environment. The amount of loaded Dox in the micelles was calculated from the released Dox at pH 3.0 where all of the loaded drugs were assumed to be released from the micelle...

In vitro cytotoxicity studies with drug-loaded micelles have also shown greater cytotoxicity above the LCST, resulting from thermally induced drug release. These results suggest that combination therapy can be implemented, using both thermosensitive systems and local hyperthermic treatment of tumors, primarily at 42°C. The coupled treatment may prove to be more... 

Figure 15 Schematic representation of the self-assembly of pH-sensitive drug-loaded micelles which was synthesized from drug conjugated amphiphilic block copolymers, that is, polyfethylene glycol)-poly(aspartate-hydrazone-adriamycin) (PEG-p(Asp-Hyd-ADR)). (Reproduced from Ref. 92. Wiley-VCH, 2004.)...

In fact for intravenous applications, it is critical that the drug-loaded micelles are stable and have a low CMC. Otherwise the micelles will dissociate into unimers upon dilution in the bloodstream causing non-targeted drug release and even toxicity. 

Fig. 13 Dispersibility of drug or drug-loaded micelles in test stents. SEM images and illustrations showing (a) the cross-sectional views of the sirolimus/chitosan-blended stent arrow in SEM image indicates the aggregates of sirolimus), and (b) the stent with sirolimus-loaded micelles. From [166] reproduced by permission of Elsevier...

Figure 7. Drug-loaded micelles prepared through self-assembly of hydrophobic drugs and amphiphilic polysaccharide derivatives.

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