In Vivo Biological Performance Of Block Copolymer Micelles

In order to successfully reach and interact with the tumor cells, the micelle-formulated drug must first circumvent the MPS. As systemic drug delivery vehicles, block copolymer micelles may serve as either solubilizers and/or true drug carriers depending on their capability for drug retention and stability in vivo. Several of the micelle formulations that have been developed for hydrophobic drugs have been shown to provide a significant increase in their water solubility.36 The use of biocompatible and biodegradable copolymers to form these micelles may result in formulations with reduced toxicity in comparison to formulations formed from some conventional surfactants or cosolvents. As a result, these copolymers may allow for higher doses of the drug to be administered, and they result in improved efficacy when compared to a conventional formulation of the drug.

Micelles that function merely as solubilizers increase the aqueous solubility of the drug, but they do not retain the drug for prolonged periods of time following systemic administration. In this way, the pharmacokinetics and biodistribution profile of the drug may remain largely unchanged. By contrast, micelles may function as true carriers that are able to retain the drug until reaching the

Red blood cells ce

Proteins Macrophages

FIGURE 17.6 In vivo fate of drug-loaded micelles following administration into the bloodstream. (a) Proteins can be adsorbed onto the micelle surface, leading to eventual clearance by the mononuclear phagocytic system (MPS). (b) The drug-loaded micelles can also circulate in the bloodstream, accumulate in the tumor inter-stitium via the enhanced permeability and retention (EPR) effect, and subsequently release the encapsulated drug to the proximal tumor cells. (c) In the case where the micelle-encapsulated drug has a high affinity for blood components, the drugs may be released from the micelle core at an accelerated rate to bind to proteins that are present in the circulation prior to reaching the tumor.

target or desired site.16,99,101 Micelles that function as carriers can result in significant improvements in the toxicity profile and/or therapeutic efficacy of the encapsulated agents.

The ability of a micelle system to function as a solubilizer or a true carrier depends on the following two factors: the stability of the micelles in vivo and the drug release profile in the presence of various blood components. The stability of block copolymer micelles in vivo depends on both thermodynamic and kinetic components as discussed in Section 17.2.

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