Polymeric Micelles for the Targeting of Hydrophobic Drugs

Kanagawa Academy of Science and Technology, Takatsu-ku, Kawasaki-shi, Kanagawa-ken, Japan 

A polymeric micelle is a macromolecular assembly that forms from block copolymers or graft copolymers, and has a spherical inner core and an outer shell (1). As shown in Fig. 1 in which an AB type block copolymer is used, a micellar structure forms if one segment of the block copolymer can provide enough interchain cohesive interactions in a solvent. Most studies of polymeric micelles both in basic and applied aspects have been done with AB or ABA type block copolymers 

Drugs can be incorporated into polymeric micelles both by chemical conjugation and physical entrapment. Drugs 

The beneficial character of low toxicity may be described as the fourth advantage. Generally, polymeric siufactants are known to be less toxic than low molecular weight siufactants such as sodiiun dodecyl sulfate. In fact, some Plxmonic block copol3rmers [poly(propylene oxide)-poly(ethylene oxide)-poly-(propylene oxide)] have been approved for intravenous injection. Further information about Plxmonic block copolymers can be obtained in another chapter written by Bronich and Kabanov. 

The fifth advantage is separated functionality. Polymeric micelles are composed of two phases inner core and outer shell. Various functions required for drug delivery systems can be shared by these structurally separated phases. Each phase can play different roles in drug delivery. As shown in 

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The second purpose underlying the incorporation of drugs into pol3rmeric micelles concerns controlled or sustained release. As the hydrophobic inner core works as a drug reservoir, the incorporated drug is released based on physical parameters such as the diffusion and partition coefficient of the drug, hydrophobicity, and the viscosity of the hydrophobic inner core. Up to now, polymeric micelles have been utilized for the purposes of targeting and solubilization only. 

Polymeric micelles Micelles consisting of amphiphilic polymers Loading hydrophobic drugs in the core for solubilization, targeted delivery, and controlled release 35,36... 

The following is an example of a novel drug-targeting system for cellular internalization using TAT. The delivery system consists of two components (1) a polymeric micelle that has a hydrophobic core of poly(L-lactic add) (PLLA) and a hydrophilic shell of PEG conjugated to TAT (TAT micelle) (2) an ultra-pH-sensitive diblock copolymer of poly(methacryloyl sulfadimethoxine) (PSD) and PEG (PSD/PEG) [199]. The final carrier system is formulated by complexation of the anionic PSD with the cationic TAT of the micelles. The complex formulation and TAT peptide can be systemically shielded. However, TAT is exposed to slightly acidic tumor pH levels due to disassembly of the complexed micelle. 

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