PEO-b-PCL

Soo et al. (2002) studied tliB vitro release of hydrophobic Luorescent probes from PEO-b PCL micelles. Micelle solutions were placed in dialysis bags (MWCO 50,000) in a stirred water bath with a constant overLow of distilled water. This maintained the release environment at near perfect sink conditions, so the limited solubility ofthe probes in the medium did not affect release kinetics. Release was determined by removing aliquots ofthe dialysis bag contents and measuring Luorescently. Soo et al. found an initial burst release of probe followed by slow diffusional release. For the probes studies, benzopyrene and Cell-Tracker-CM-Dil, diffusion constants were ofthe order 10"15 cnnP/s. 

Savb et al. (2006) report a method to evaluate micelle integrity irottitro andin vivo. PEO-b-PCL micelles were synthesized with a Luorogenic dye, Luorescein-5-carbonyl azide diacetate, covalently attached to the PCL block. In the hydrophobic core of intact micelles, the dye remained... 

Murine Pharmocokinetics and Biodistribution of Cyclosporine A in a PEO-b-PCL Micelle Formulation and the Cremophor Preparation (Sandimmune , Novartis Pharmaceuticals)... 

The degradable SPU bioelastomers from PCL-b-PEO-b-PCL triblock copolymers as soft segments, 1,4-BDI and peptide Ala-Ala-Lys (AAK) chain... 

Only a few publications deal with ABC triblock copolymers where two of the blocks are able to crystallize. The systems that have been investigated include PS-b-PE-b-PCL [94,98], PE-b-PS-6-PCL [94], PS-fc-PEO-fo-PCL [30,134-136] and PE-fo-poly(ethylene-propylene)-fr-PEO [101,119] (see also Table 1). 

Fig. 16 DSC a cooling and b heating scans (10°Cmin 1) of the PS-fc-PEO diblock precursor and PS-fc-PEO-fc-PCL triblock copolymer. (Reprinted with permission from [30]. Copyright 2001 American Chemical Society)...

Several of the ABC triblock copolymers with two crystallizable blocks that have been studied include PE as one of the crystallizable components. The PE block can be found either at the end (PE-fo-PS-b-PCL [94], PE-fr-PEP-fo-PEO [101,119]) or at the center (PS-fr-PE-fr-PCL [98]). When the PE block is located at the center of the copolymer, as is the case in PS-fo-PE-fr-PCL triblock copolymers [94], there are higher constraints on the PE block owing to the absence of free ends. If the PE block is a minor component, confined crystallization with possible homogeneous nucleation is usually encountered. It may be possible that when the PE block does not have free ends, it may be... 

The technique of self-nucleation [75] can be very useful to study the nucleation and crystallization of block copolymer components, as already mentioned in previous sections. In block copolymers, factors like the volumetric fraction and the degree of segregation affect the type of confinement and therefore modify the self-nucleation behavior. In the case of semicrystalline block copolymers, several works have reported the self-nucleation of either one or both crystallizable components in PS-fc-PCL, PS-b-PB-b-PCL, PS-b-PE-b-PCL, PB-fr-PIB-fr-PEO, PE-fr-PEP-fr-PEO, PS-fc-PEO, PS-h-PEO-h-PCL, PB-b-PEO, PB/PB-fc-PEO and PPDX-fc-PCL [29,92,98,99,101-103,134] and three different kinds of behavior have been observed. Specific examples of these three cases are given in the following and in Table 5 ... 

Floudas et al. [135] also studied the isothermal crystallization of PEO and PCL blocks within PS-b-PEO-h-PCL star triblock copolymers. In these systems the crystallization occurs from a homogeneous melt Avrami indexes higher than 1 are always observed since the crystallization drives structure formation and does not occur under confined conditions. A reduction in the equilibrium melting temperature in the star block copolymers was also observed. 

Fig. 12. Schematic illustration of the morphology formed by blends and copolymers of two crystallizable polymers (after [43]). a a PEO/PCL blend, b in a PCL-PEO-PCL triblock. In the blend, PEO and PCL are phase separated into domains in which each homopolymer crystallizes in a lamellar texture. In the copolymer, PEO and PCL blocks crystallize in the same domain due to chain connectivity...

Among these reactions, the Cu(l)-catalyzed azide-alkyne cycloaddition (CuAAC) is the most widely used. This reaction has been implemented for the preparation of segmented block copolymers from polymerizable monomers by different mechanisms. For example, Opsteen and van Hest [22] successfully prepared poly(ethylene oxide)-b-poly(methyl methacrylate) (PEO-b-PMMA) and PEO-b-PSt by using azide and alkyne end-functionalized homopolymers as the click reaction components (Scheme 11.2). Here, PEO, PSt, and PMMA homopolymers were obtained via living anionic ring-opening polymerization (AROP), atom transfer radical polymerization (ATRP), and postmodification reactions. Several research groups have demonstrated the combination of different polymerization techniques via CuAAC click chemistry, in the synthesis of poly(e-caprolactone)-b-poly(vinyl alcohol) (PCL-b-PVA)... 

In the literature many differences can be found in the temperature range used for the study of the crystalUzation and melting processes of PEO and PCL based AB diblock and ABA triblock copolymers. When the studies are performed above room temperature, an important fraction of the blocks may remain amorphous [8-11, 14, 16] however, most authors report that when the study is extended at temperatures below Tg, both blocks can crystallize [13-15,17]. In the case of ABA triblock copolymers, it has been found that the B-block remains amorphous when its content is lower than 10%, or its molecular weight is very low. Piao et al. [17] and He et al. [18,19] synthesized either poly(e-caprolactone)-6-poly(ethylene oxide)-6-poly(e-caprolactone) ABA triblock copolymers, as well as poly(ethylene oxide)-6-poly(e-caprolactone) AB diblock copolymers. They used poly(ethylene glycol) (PEG) as precursor and a calcium catalyst. Then, they characterized the materials by using NMR, DSC, WAXS and Polarized Optical Microscopy (POM). Cooling DSC scans carried out by He et al. [18] in AB diblock copolymers of different compositions are presented in Fig. 13.1. 

Common SS include polyethers, polyesters and polyalkyl glycols with glass transition temperatures in the range of -70°to -30°C. Commonly used macrodiols in the PUs synthesis are polyalkyl-diols, such as polyisobutylene diol [70], polybutadiene (PBU) [20, 71], or oligo-butadiene diols [72] as well as hydrogenated polybutadiene diol [20] polyether diols polytetrahydrofuran (PTHF or PTMO) [50-52], polyethylene glycol (PEG) or (PEO) [73], polypropyleneoxide (PPO) [73] or mixed blocks of them PEO-PPO-PEO [74] and PPO-THF [54] polyester diols poly(ethylene adipate) (PEA) [4,20], poly(butylene adipate) (PBA) [20, 73], and latterly polycaprolactone diol (PCL or PCD) [75], polyalkylcarbonate polyol [20] or mixed blocks of them, for example poly(carbonate-co-ester)diol [76], poly(hexamethylene-carbonate)diol [77], as well as poly(hexamethylene-carbonate-co-caprolactone)diol [78] and a mixed block copolymer of polyether and polyester blocks PCL-b-PTHF-b-PCL [79]. Examples schemes of macrodiols are shown in Eig. 1.9. 

Figure 2 Example polymers that can undergo phase separation, (a) Poly(ethylene oxide)-f)-poly(butylene oxide), (PEO-f)-PBO) (b) poly(ethyleneoxide)-fc-poly(styrene), (PEO-i>-PS) (c) poly(styreneFi -poly(4-vinylpyridine), (PS-i>-P4VP) (d) poly(ethylene oxide)-f)-poly(caprolactone), (PEO-fc-PCL) (e) poly(ethylene oxide)-f)-poly(butadiene), (PEO-f)-PB) and (f) polyfacrylic acid)-fc-poly(styrene), (PAA-1>-PS).

Figure 9 Top cartoon representations of a spherical micelle, a wormlike micelle, and a vesicle. The red blocks represent the solvophilic blocks, and the blue blocks represent the solvophobic blocks. Bottom example TEM images showing diffa-ent micelle morphologies adopted by block copolymers in solution, (a) Spherical micelles formed from polyfethylene oxide)-f>-polycaprolactone (PEO-f>-PCL) copolymers.(b) Wormlike micelles, vesicles, and octupi formed by mixing PEO-fc-polybutadiene (PEO-fc-PB) block copolymers. (Reproduced from Ref. 32. American Chemical Society, 2004.) (c) Vesicles formed from PEO-f>-PCL copolymers. (Reproduced from Ref. 33. Royal Society of Chemistry, 2011.) (d) Multicompartment micelles formed from a triblock copolyma-. (Reproduced from Ref. 34. American Chemical Society, 2010.) (e) Stomatocytes formed using PEO-f>-polystyrene (PEO-f>-PS) copolyma-s. (Reproduced from Ref. 35. American Chemical Society, 2010.) (f) Toroidal micelles coexisting with cylindrical micelles and sphaical micelles formed from poly(acrylic acid)-f>-poly(methacrylic acid)-fc-PS (PAA-f>-PMA-f>-PS) triblock copolymers. (Reproduced from Ref. 36. Royal Society of Chemistry, 2009.)...

A-B-C structures are another possibility to develop new properties of polymeric nanocarriers for drug release. This approach was examined for instance by Kim ef a/. [ 310 ], with PEO-PPO-PCL triblock copolymers, by Deng et al. [ 108] with PEG-b-PLLA-b-PLGA and by Gadzinowski etal. [311] with PEO-b-poly(glycidol)-b-PLLA. 

Shen et al. [50] carried out a detailed investigation in the MIV mixer, studying the incorporation of (5-carotene and polyethyleneimine (PEI) selected as model drug and cationic macromolecule various copolymers in different physical states were selected an amorphous one, poly(ethylene oxide)-l>-poly(styrene) (PEO-b-PS), a semicrystalline one, poly(ethylene oxide)-b-poly(e-caprolactone) (PEG-fc-PCL), and an ionic copolymer, poly(ethylene oxide)-b-poly(acrylic acid) (PEG-b-PAA) this also allowed the investigation of the influence of the type of interaction forces, in addition to hydrodynamics and supersaturation rate. 

Figure 14 The schematic representation and TEM images of PEO-i>-PCL/PVPh blends showing different morphologies in (a) pristine block copolymer, (b) 20 wt%, and (e) 40wt% of PVPh concentration. Salim et al. [30]. Reproduced with permission of American Chemical Society.

Allen, C., Eisenberg, A., et al. PCL-b-PEO micelles as a delivery vehicle for FK506 Assessment of a functional recovery of crushed peripheral nerve. Drug Del. 7(3) 139-145, 2000. 

The technique of self-nucleation can be very useful to study the nucleation and crystallization of block copolymers that are able to crystallize [29,97-103]. Previous works have shown that domain II or the exclusive self-nucleation domain disappears for systems where the crystallizable block [PE, PEO or poly(e-caprolactone), PCL] was strongly confined into small isolated MDs [29,97-101]. The need for a very large number of nuclei in order to nucleate crystals in every confined MD (e.g., of the order of 1016 nuclei cm 3 in the case of confined spheres) implies that the amount of material that needs to be left unmolten is so large that domain II disappears and annealing will always occur to a fraction of the polymer when self-nucleation is finally attained at lower Ts. This is a direct result of the extremely high number density of MDs that need to be self-nucleated when the crystallizable block is confined within small isolated MDs. Although this effect has been mainly studied in ABC triblock copolymers and will be discussed in Sect. 6.3, it has also been reported in PS-b-PEO diblock copolymers [29,99]. 

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