Polymer micelles hydrophilic block copolymers

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 this contribution, we describe our recent experimental and theoretical findings on complex coacervate core micelles. We have investigated the co-assembly of several types of oppositely charged ionic-hydrophilic block copolymers into mixed micelles. In particular, we have focused on chain mixing/segregation in the micellar corona as a function of monomer type and (the ratio between the) chain length of the polymer blocks in the corona. Our aim has been to employ co-assembly in such systems as a route towards formation of reversible Janus micelles. These are micelles with a corona that exhibits two distinguishable sides (hemispheres in the case... 

Now that we have established the requirements for the formation of reversible Janus micelles, we turn our attention to the choice of ionic-hydrophilic block copolymers. The ionic blocks have to be oppositely charged to ensure co-assembly in aqueous solutions, whereas the neutral blocks have to be water-soluble. Furthermore, the unlike water-soluble polymer blocks need to segregate, not mix within the micellar corona. Since the classical works of Flory and Huggins, extended by Scott to describe binary polymer solutions [58], it is well known that two unlike polymers... 

We have shown that a combination of four simple building blocks (i.e. monomers) and exclusively non-covalent interaction forces, achieved via the co-assembly of fully water-soluble double hydrophilic block copolymers, results in mixed micelles in aqueous solutions. The chemically unlike polymer chains in the micellar corona may give rise to various coronal microstructures, ranging from mixed to segregated, in either the radial or lateral direction, or in both. Hence, co-assembly of charged block copolymers can result in the spontaneous formation of reversible Janus micelles. 

The coupling of polymeric building blocks can result in amphi-philicity when one block is hydrophilic and the other one is hydrophobic. In dilute solution, miaophase separation of amphiphilic block copolymers is known to drive self-assembly to form equilibrium morphologies, such as spherical and cylindrical micelles as well as vesicles. " The exact stmcture is determined by the 3D shape of the amphiphile. Block copolymers can also be designed to switch their amphiphilidty on or off according to external stimuli. In aqueous systems, these polymers are known as double hydrophilic block copolymers. ... 

Hydrophilic-hydrophilic also called double-hydrophilic block copolymers, consist of water-soluble blocks of different chemical nature. In aqueous solution they behave as unimers like classical polymers or polyelectrolytes, whereas their amphiphilic characteristics, such as surface activity and micelle formation, only appear under the influence of a given external stimuli, mainly temperature, pH or ionic strength changes. Micellization of these copolymers can further be induced by complex formation of one of their blocks, either by electrostatic interaction with oppositely charged polymers, by hydrophobic interactions such as with surfactants, or by insolubilization in the presence of metal derivatives. These polymer intercomplexes, mainly polyion complexes (PIC), with their application possibilities will be outlined in more detail in Section 7.3.13. 

Y-shaped double-hydrophilic block copolymers, with a poly(EO-co-PO) sequence and two blocks of various hydrophilic methacryKc polymers, were synthesized by an elaborated ATRP technique by Armes and co-workers [239]. pH and thermal stimulus-responsive micelles could be obtained by these authors. 

Amphiphilic/associating vater-soluble polymers, in particular block copolymers and hydrophobically modified vater-soluble polymers, have been studied extensively during the last decade and are vell understood [50, 51]. For graft copolymers that are hydrophobically modified vater-soluble polymers, vhich are common as thickeners and dispersants, the self-assembly is very different than for block copolymers. For such graft copolymers there is a strong opposing force due to the hydrophilic polymer backbone. In particular, due to the entropic penalty in folding the polymer chain, only small discrete hydrophobic micro-domains ( micelles ) are formed. 

The formation of polymeric capsules can also be achieved by the cross-linking of self-assembled amphiphilic block copolymers [85]. The hydrophobic section of the polymer in an aqueous solution will tend to aggregate on the interior of the micelle, whereas the hydrophilic ends will form the outer shell of the micelle. If the hydrophilic end is appropriately functionalized, it can be cross-linked, giving a polymeric shell. The overarching concept is shown in Figure 5.10. 

Many kinds of nonbiodegradable vinyl-type hydrophilic polymers were also used in combination with aliphatic polyesters to prepare amphiphilic block copolymers. Two typical examples of the vinyl-polymers used are poly(/V-isopropylacrylamide) (PNIPAAm) [149-152] and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) [153]. PNIPAAm is well known as a temperature-responsive polymer and has been used in biomedicine to provide smart materials. Temperature-responsive nanoparticles or polymer micelles could be prepared using PNIPAAm-6-PLA block copolymers [149-152]. PMPC is also a well-known biocompatible polymer that suppresses protein adsorption and platelet adhesion, and has been used as the hydrophilic outer shell of polymer micelles consisting of a block copolymer of PMPC -co-PLA [153]. Many other vinyl-type polymers used for PLA-based amphiphilic block copolymers were also introduced in a recent review [16]. 

Polymer micelles are nanometer sized (usually several tens of nanometers) self-assembled particles having a hydrophobic core and hydrophilic outer shell composed of amphiphilic AB- or ABA-type block copolymers, and are utilized as drug delivery vehicles. The first polymer micelle-type drug delivery vehicle was made of PEG-b-poly(aspartic acid) (PEG-b-PAsp), immobilizing the hydro-phobic anticancer drugDXR [188-191]. After this achievement by Kataoka et al., a great amount of research on polymer micelles has been carried out, and there are several reviews available on the subject [192-194]. 

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... 

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