Block polymeric micelles

Bae Y, Kataoka K (2009) Intelligent polymeric micelles from functional poly(ethylene glycol)-poly(amino acid) block copolymers. Adv Dmg Deliv Rev 61 768-784... 

Fig. 30 Types of nanocarriers for drug delivery, (a) Polymeric nanoparticles polymeric nanoparticles in which drugs are conjugated to or encapsulated in polymers, (b) Polymeric micelles amphiphilic block copolymers that form nanosized core-shell structures in aqueous solution. The hydrophobic core region serves as a reservoir for hydrophobic drugs, whereas hydrophilic shell region stabilizes the hydrophobic core and renders the polymer water-soluble.

In dilute aqueous solutions, copolymers having hydrophobic and hydrophilic parts may form polymeric micelles, i.e. stable particles with a core-shell structure. The association of the hydrophobic parts of the block copoly-... 

Fig. 11 Experimentally determined grafting distance b as function of degree of polymerization of insoluble block for polyelectrolyte block copolymer micelles at different salt concentrations salt free, o 0.3mol/l, 1 mol/1. Reprinted with permission from [15]. Copyright (2004) Springer... 

In previous sections, much emphasis has been put on block copolymer micelles with a spherical morphology. It was shown in Sect. 5 that the characteristic sizes of both the spherical core and corona of block copolymer micelles can be precisely adjusted by essentially controlling the chemical nature and the degree of polymerization of the constituent blocks. For several applications of block copolymers micelles including, e.g., micellar templating... 

The discovery of new controlled polymerization techniques in the mid-1990s and the progress achieved in living polymerization toward well-defined block copolymers with complex topologies have certainly played a key role in the development of block copolymer micelles. 

We have shown that polymeric micelles constmcted of block copolymers of poly(ethylene oxide) (PEG) and poly(L-asparate) containing the anticancer dmg (adriamycin, ADR) selectively accumulate at solid tumor sites by a passive targeting mechanism. This is likely due to the hydrophilicity of the outer PEG chains and micellar size (<100 nm) that allow selective tissue interactions [17,18]. Polymeric micelle size ranges are tailored during polymer synthesis steps. Carefully selection of block polymer chemistry and block lengths can produce micelles that inhibit nonselective scavenging by the reticuloendothelial system (RES) and can be utilized as targetable dmg... 

Polymeric micelles with selected chemistries and molecular architecture of block copolymers, such as PIPAAm-CigHgs, PIPAAm-PSt, PIPAAm-PBMA, and PIPAAm-PLA micelles, showed the same LCST and the same thermoreponsive phase transition kinetics as those for PIPAAm irrespective of the hydrophobic segment incorporation. This confirms two points (a) that hydroxyl groups or amino goups of PIPAAm termini completely react with the hydrophobic segment end groups and (b) that the block copolymers form core-shell micellar structures with hydrophobic iimer cores completely isolated from the aqueous phase. 

Thermoresponsive polymeric micelles with PIPAAm block copolymers can be expected to combine passive spatial targeting specificity with a stimuli-responsive targeting mechanism. We have developed LCSTs of PIPAAm chains with preservation of the thermoresponsive properties such as a phase transition rate by copolymerization with hydrophobic or hydrophilic comonomers into PIPAAm main chains. Micellar outer shell chains with the LCSTs adjusted between body temperature and hyperthermic temperature can play a dual role in micelle stabilization at a body temperature due to their hydrophilicity and initiation of drug release by hyperthermia resulting from outer shell structural deformation. Simultaneously, micelle interactions with cells could be enhanced at heated sites due... 

Chung, J. E., Yokoyama, M., Yamato, M., Aoyagi, T., Sakurai Y., and Okano, T. Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(A-isopropylacrylamide) and poly(butylmethacrylate), J. Contr. Rel, 1999, 62, 115-127. 

Application of amphiphilic block copolymers for nanoparticle formation has been developed by several research groups. R. Schrock et al. prepared nanoparticles in segregated block copolymers in the sohd state [39] A. Eisenberg et al. used ionomer block copolymers and prepared semiconductor particles (PdS, CdS) [40] M. Moller et al. studied gold colloidals in thin films of block copolymers [41]. M. Antonietti et al. studied noble metal nanoparticle stabilized in block copolymer micelles for the purpose of catalysis [36]. Initial studies were focused on the use of poly(styrene)-folock-poly(4-vinylpyridine) (PS-b-P4VP) copolymers prepared by anionic polymerization and its application for noble metal colloid formation and stabilization in solvents such as toluene, THF or cyclohexane (Fig. 6.4) [42]. 

Bes L, Angot S, Limer A, Haddleton DM. Sugar-coated amphiphilic block copolymer micelles from living radical polymerization recognition by immobilized lectins. Macromolecules 2003 36 2493-2499. 

Au NPs have been synthesized in polymeric micelles composed of amphiphilic block copolymers. Poly(styrene)-block-poly(2-vinylpyridine) in toluene has been used as nanocompartments loaded with a defined amount of HAuCl4 and reduced with anhydrous hydrazine. The metal ions can be reduced in such a way that exactly one Au NP is formed in each micelle, where each particle is of equal size between 1 and 15 nm [113]. In another example, the addition of HAuCfi to the triblock copolymer (PS-b-P2VP-b-PEO) (polystyrene-block-poly-2-vinyl pyridine-block-polyethylene oxide) permits the synthesis of Au N Ps using two different routes, such as the reduction of AuC14 by electron irradiation during observation or by addition of an excess of aqueous NaBH4 solution [114]. 

Pharmaceutical research on polymeric micelles has mainly focused on two kinds of block copolymers, namely, AB block copolymers or diblock copolymers and ABA or BAB block copolymers known as triblock copolymers (Bader et al., 1984 Yokoyama et al., 1990,1991 Kwon and Okano, 1996, 1999 Kwon, 1998, 2003 Alakahov and Kabanov, 1998). The most common hydrophilic block (A) of the block copolymers is polyethylene oxide (PEO). This polymer is highly hydrated through hydrogen bonding and sterically stabilizes surfaces of the polymeric micelles in aqueous systems. 

Yokoyama et al. (1998) reported the procedures for chemical conjugation of adriamycin (ADR) into polymeric micelles that was based on a reference (Yokoyama et al., 1994) with some modiLcations The copolymer used by Yokoyama et al. (1998) was polyethylene gljBept)ly(aspartic acid) block copolymer (PEG-P(Asp)). Molecular weight of the (PEG) chain and the (P(Asp)) chain was... 

Block copolymer micelle formulations of doxorubicin and paclitaxel are both in Phase l/ll trials for the treatment of advanced cancers. Aliabadi and Lavasanifar (2006) recently compiled a review of the clinical status of polymeric micelle systems for anticancer agent delivery. 

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