J.Rodriguez-Hemdndez et al./Prog.Polym.Sci.30(2005)691-724 701 The kataoka group.which has shown great interes the effect of the surface charge on the pharmacoki in the use of micelles as potential drug carriers [42]. netic behavior and the influence of the peptidic demonstrated that micelles can indeed act as excellent receptor on drug delivery(Fig.8). vehicles for delivery because side effects can be An interesting example of the solubilization/ alleviated.the drug being protected from degradation encapsulation capability of block copolymers was and its deposition site better targeted.With the reported by Jenekhe et al.[45].They prepared increase in selectivity the amount of drug admini- spherical micelles from rod-coil block copolymers strated can be precisely controlled and thus reduced of poly(phenylquinoline)-b-poly(styrene)(PPQ-PS) [43].The Kataoka system is based on poly(ethylene using binary solvents that are selective for the rod- type block.The resulting aggregates exhibit the copolymers wi of thi re of an ultra large interio vol ze (o arge mo lecule nm stability he solu equired for a pr long-term Coo and in the PBLA the 06 once io as Ab ploited the idea of using cet ulate .The poly(ethylene oxide)-b-poly(D.L-lactide)blockc encapsulation Ivmers [441.The a-a cetal group i PE demonstrated to have nces for the micellization and self-asse transformed into an aldehyde g up and conjugated of ther olymers.Regular hollow spheres that increas with a peptide segment of phenylalanine (Phe)or in size (about six-times)and in aggregation number tyrosil-glutamic acid (Tyr-Glu).The authors analyzed were thus obtained.The self-organized materials (ii)Cenjugation+HaN- CHi-NH
The Kataoka group, which has shown great interest in the use of micelles as potential drug carriers [42], demonstrated that micelles can indeed act as excellent vehicles for delivery because side effects can be alleviated, the drug being protected from degradation and its deposition site better targeted. With the increase in selectivity the amount of drug administrated can be precisely controlled and thus reduced [43]. The Kataoka system is based on poly(ethylene oxide)-b-poly(b-benzylaspartate) (PEO-PBLA) block copolymers with PEO as corona. Advantages of this system are related to its small micellar size (diameter w10–100 nm) and its long-term stability, which is required for a prolonged circulation time. This carrier system possesses alcohol functions in the PBLA block that can be used to attach a desired moiety. Other studies exploited the idea of using a-acetoxypoly(ethylene oxide)-b-poly(D,L-lactide) block copolymers [44]. The a-acetal group in PEO was transformed into an aldehyde group and conjugated with a peptide segment of phenylalanine (Phe) or tyrosil-glutamic acid (Tyr-Glu). The authors analyzed the effect of the surface charge on the pharmacokinetic behavior and the influence of the peptidic receptor on drug delivery (Fig. 8). An interesting example of the solubilization/ encapsulation capability of block copolymers was reported by Jenekhe et al. [45]. They prepared spherical micelles from rod-coil block copolymers of poly(phenylquinoline)-b-poly(styrene) (PPQ-PS) using binary solvents that are selective for the rodtype block. The resulting aggregates exhibit the unique feature of an ultra large interior volume which could be used to encapsulate large molecules like C60 and C70 fullerenes. The solubilization was independent of the mass ratio between the two blocks and of the concentration as well. Absorption spectroscopy was used to analyze the capability of these block copolymers to encapsulate fullerenes. The encapsulation process was demonstrated to have consequences for the micellization and self-assembly of the polymers. Regular hollow spheres that increase in size (about six-times) and in aggregation number were thus obtained. The self-organized materials Fig. 8. Kataoka’s approach to the conjugation of amino acids on the micellar surface using PEG-b-PLLA block copolymers. Adapted from Ref. [44]. J. Rodrı´guez-Herna´ndez et al. / Prog. Polym. Sci. 30 (2005) 691–724 701
702 J.Rodriguez-Herndndez et al.Prog.Polvm.Sci.30 (2005)691-724 for electronic optoelectronic,or pho ferent as>mmetric amphip之n polyst 242 Vesicles lv(4-vinvl ridinium met Vesicles are nanometer-sized 'bags'whose double-layer outer membrane encloses an inner ide).and polystyrene-b-poly(methyl methacrylate)-b- volume.Because of the double layer,that recalls the poly(acrylic acid).From the study of these systems structure of lipids in membrane cells,vesicles are also the authors classified systematically the different called polymersomes (polymer-based liposomes).In obtained,shown in Fig.9.and gave some aspects.polymersomes can be on about the condit tions require 'giant nor ing the Dische ated vesicles in a hilic oxide)-h ties and annlications have beer poly(ethylene)(PEO-b-PE) and poly(ethyle published recently 7a.461.Amphiphilic block copo oxide)-b-polybutadiene (PEO-b-PB)block copoly lymers can form various vesicular architectures in mers with various block compositions [48].They solution.They include uniform common vesicles. unalyzed the mechanical properties and stability of large polydisperse vesicles.entrapped vesicles.or the vesicles in various media and over a wide range hollow concentric vesicles. of temperature.With in vitro experiments they t thes vesicles are inert toward variou aving cells 1000m 300nm
prepared in this way may be of interest for electronic, optoelectronic, or photonic applications. 2.4.2. Vesicles Vesicles are nanometer-sized ‘bags’ whose double-layer outer membrane encloses an inner volume. Because of the double layer, that recalls the structure of lipids in membrane cells, vesicles are also called polymersomes (polymer-based liposomes). In some aspects, polymersomes can be considered as ‘giant nonbiological liposomes’. Excellent reviews describing the various means to generate vesicles from amphiphilic polymers in various media, and including their properties and applications, have been published recently [7a,46]. Amphiphilic block copolymers can form various vesicular architectures in solution. They include uniform common vesicles, large polydisperse vesicles, entrapped vesicles, or hollow concentric vesicles. In a recent review, Eisenberg [47] et al. described the formation of multiple morphologies from six different asymmetric amphiphilic block copolymers: polystyrene-b-poly(acrylic acid), polystyrene-bpoly(ethylene oxide), polybutadiene-b-poly(acrylic acid), polystyrene-b-poly(4-vinylpyridinium methyl iodide), polystyrene-b-(4-vinylpyridinium decyl iodide), and polystyrene-b-poly(methyl methacrylate)-bpoly(acrylic acid). From the study of these systems the authors classified systematically the different morphologies obtained, shown in Fig. 9, and gave additional information about the conditions required for the formation of each structure. The Bates and Discher generated vesicles in a broad range of sizes from poly(ethylene oxide)-bpoly(ethylene) (PEO-b-PE) and poly(ethylene oxide)-b-polybutadiene (PEO-b-PB) block copolymers with various block compositions [48]. They analyzed the mechanical properties and stability of the vesicles in various media and over a wide range of temperature. With in vitro experiments they showed that these vesicles are inert toward various living cells. Fig. 9. Representative images of the several classes of vesicles: (A) small uniform, (B) large polydisperse, (C) entrapped, (D) hollow concentric, (E) ‘onions,’ (F) vesicles with tubes in the wall. Adapted from Ref. [47]. 702 J. Rodrı´guez-Herna´ndez et al. / Prog. Polym. Sci. 30 (2005) 691–724