Polymersomes preparation

Hammer and coworkers prepared PEG-h-PCL polymersomes entrapping DXR (Fig. 11a). The release of DXR from the polymersomes was in a sustained manner over 14 days at 37 °C in PBS via drug permeation through the PCL membrane, and hydrolytic degradation of the PCL membrane [228]. The release rate of encapsulated molecules from polymersomes can be tuned by blending with another type of block copolymer [229]. Indeed, the release rate of encapsulated DXR from polymersomes prepared from mixtures of PEG- -PLA with PEG- -PBD copolymers increased linearly with the molar ratio of PEG- -PLA in acidic media (Fig. lib). Under acidic conditions, the PLA first underwent hydrolysis and, hours later, pores formed in the membrane followed by final membrane... 

The permeability of polymersome membranes for a given solute has been reported to be at least 10 times smaller compared to common phosphohpid membranes (8). Retention of encapsulants (eg dextrans, sucrose, physiological saline) over periods of months has been observed for small 100 nm polymersomes prepared by liposome-type extrusion techniques (49) as well as with 10 p.m giant vesicles. Permeability and membrane hydration have been shown to be inversely related to the bending modulus (165). It is suggested that membrane permeability and membrane hydration are related to the ability of the membrane to locally bend so as to create holes for solute permeation. 

Recently, we have also prepared nanosized polymersomes through self-assembly of star-shaped PEG-b-PLLA block copolymers (eight-arm PEG-b-PLLA) using a film hydration technique [233]. The polymersomes can encapsulate FITC-labeled Dex, as model of a water-soluble macromolecular (bug, into the hydrophilic interior space. The eight-arm PEG-b-PLLA polymersomes showed relatively high stability compared to that of polymersomes of linear PEG-b-PLLA copolymers with the equal volume fraction. Furthermore, we have developed a novel type of polymersome of amphiphilic polyrotaxane (PRX) composed of PLLA-b-PEG-b-PLLA triblock copolymer and a-cyclodextrin (a-CD) [234]. These polymersomes possess unique structures the surface is covered by PRX structures with multiple a-CDs threaded onto the PEG chain. Since the a-CDs are not covalently bound to the PEG chain, they can slide and rotate along the PEG chain, which forms the outer shell of the polymersomes [235,236]. Thus, the polymersomes could be a novel functional biomedical nanomaterial having a dynamic surface. 

The formation of polymersomes from water in- oil-in-water drops. Initially, a double emulsion consisting of single aqueous drops within drops of a volatile organic solvent ( oil ) is prepared using a microcapillary device. Amphiphilic diblock copolymers dissolved in the middle phase assemble into monolayers at the oil-water interfaces. Evaporation of the solvent then leads to the formation of polymer bilayers (polymersomes). 

Block copolymer vesicles, or polymersomes, are of continued interest for their ability to encapsulate aqueous compartments within relatively robust polymer bilayer shells (Fig. 7) [66, 67]. Eisenberg and coworkers were the first to report the formation of block copolymer vesicles from the self-assembly of polystyrene-h-poly(acrylic acid) (PS-h-PAA) block copolymers. They also have described the formation of a wide range of vesicle architectures in solution from the self-assembly of five different block copolymers PS-h-PAA. PS-h-PMMA, PB-h-PAA, polystyrene-h-poly(4-vinyIpyridinium methyl iodide), and polystyrene-h-(4-vinylpyridinium decyl iodide) [68]. Small uniform vesicles, large polydisperse vesicles, entrapped vesicles, hollow concentric vesicles, onions, and vesicles with hollow tubes in the walls have been observed and the formation mechanism discussed. Since vesicles could be prepared with low glass transition polymers such as PB [69, 70] and PPO [71], it has been established than these structures are thermodynamically stable and not trapped by the glassy nature of the hydrophobic part. 

Du and coworkers [122] prepared vesicles from poly(2-(methacryloyloxy)ethyl phosphorylcholine-fe-2-(diisopropylamino)ethyl methacrylate (PMPC-fe-PDPA) directly in water without any cosolvents. These vesicles are stable at physiological pH and completely dissociate below pH 6. Moreover, they are very close analogues of conventional liposomes due to the biomimetic phosphorylcholine motif. Further research demonstrated that these polymersomes are efficient systems for pH-controlled encapsulation and delivery of DNA [218],... 

Recently, the group of Battaglia used poly(2-(methacryloyloxy)ethyl-phosphorylcholine)-copoly(2-(diisopropylamino)ethyl methacrylate) (PMPC-PDPA) diblock copolymers to prepare biomimetic and pH-sensitive polymersomes for gene delivery [218]. These formulations encapsulated and released DNA in a pH-controlled manner. Notably, the pH drop was sufficient to trigger the transition from DNA-loaded vesicles to DNA-copolymer complexes. 

It is possible to prepare diblock, triblock, multiblock, random block, star and graft copolymers simply by controlling their synthesis [7]. Such diversity of chemical architecture can be exploited for the design of different polymersomes membranes with diverse degree of entanglements and sub-structures. Figure 2 emphasizes the potential bilayer assembly depending on the molecular architecture of the copolymer utilized. 

Pang Z, Lu W, Gao H, Hu K, Chen J, Zhang C, Gao X, Jiang X, Zhu C (2008) Preparation and brain delivery property of biodegradable polymersomes conjugated with 0X26. J Contr Release 128 120-127... 

Polymersomes, self-assembled polymer shells composed of block copolymer amphiphiles. These synthetic amphiphiles with amphiphilicity similar to lipids constitute a new class of drug carriers. They are spontaneously formed in aqueous media, as unilamellar vesicles up to tens of microns in diameter. Amphiphilic block copolymers form a range of self-assembled aggregates including spherical, rod-like, tubular micelles, lamellae, or vesicles, depending on polymer architectnre and preparation conditions. Polymers having low hydrophobicity (less than 50%) favor the formation of micelles, however, intermediate level of hydrophobicity (50%-80%) favors the formation of vesicles. Polymeric vesicles, which have a liposome-like structure with a hydrophobic polymer membrane and hydrophilic inner cavity, are called polymersomes. 

Biodegradable Polymers Used in Preparation of Polymersomes and Micelles and Their Applications... 

The potential of self-assembly of functional block copolymers with the aim to confine functionality in a specific compartment is well demonstrated by the formation of functional polymersomes (Section 6.1.1.2). As an example, Meier et al. [20] prepared polymersomes composed of poly(dimethylsiloxane)- /oc -poly(2-methyloxazoline) diblock copolymers that had been modified... 

Various amphiphilic polymers with a defined block length ratio of about 1 2 polar/nonpolar have so far been applied to the preparation of polymersomes (Fig. 6.3) [6, 7]. 

Polymersomes can be further applied as synthetic cell organelles for the modeling of simple cell processes. For example, it was possible to prepare polymersomes with the integrated membrane protein LamB, which allowed the docking of the bacteriophage lambda at the polymersome surface. This system enabled the study of DNA transfer from the bacteriophage into the polymersome via the membrane protein [8]. 

Another concept is the preparation of responsive polymersome membranes, which are further cross-linked for stabilization. This concept allows for preservation of the general polymersome capsule structure upon switching polarity but leads to a more leaky membrane structure, resulting in enhanced membrane transport (Fig. 6.5).This can be achieved by incorporating pH-sensitive blocks, for example, in photo-cross-linkable polymersomes. The membrane of the vesicle is then formed spontaneously as double layer at suitable pH from the block copolymer containing the photo-cross-linkable units and is subsequently cross-linked in the collapsed state. Upon acidification, the nonpolar blocks are protonated and transformed into a polar block. Therefore, the polymersome would like to disintegrate but is linked by chemical bonds, and... 

Nanoparticles are classified into two groups according to preparation techniques, which are nanocapsules and nanospheres (see Figure 11.3). Nanocapsules are vesicular systems enveloped with a polymeric membrane film. The active substances are encapsulated in the inner core. Nanocapsules consist of oily core and unilayer polymeric membrane or aqueous core and double layer polymeric membrane, called nanocapsule and polymersome, respectively. Nanospheres are matrix-type colloidal particles and they do not have an oily core, in contrast to nanocapsules. Nanoparticles can be prepared directly from cationic polymers such as chitosan, PEI or PLL. These cationic nanoparticles have been studied extensively for nucleic acid delivery in particular. 

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