Polymersome-encapsulated

Arifin DR, Palmer AF. Polymersome encapsulated hemoglobin a novel type of oxygen carrier. Biomacromolecules 2005 6(4) 2172-81. 

Rameez S, Alosta H, Palmer AF. Biocompatible and biodegradable polymersome encapsulated hemoglobin a potential oxygen carrier. Bioconjug Chem 2008 19(5) 1025-32. 

Numerous experimental therapeutics have shown potency in vitro however, when they are tested in vivo, they often lack significant efficacy. This is often attributed to unfavorable pharmacokinetic properties and systemic toxicity, which limit the maximum tolerated dose. These limitations can be overcome by use of drug carriers. Two general types of carrier systems have been designed drug conjugation to macromolecular carriers, such as polymers and proteins and drug encapsulation in nanocarriers, such as liposomes, polymersomes and micelles. 

Fig. 10 (a) Chemical structure of PEG-6-PCL copolymer, (b) CLSM image of PEG-6-PCL polymersomes containing membrane-encapsulated Nile Red (2 mol%) and aqueous entrapped Calcein dyes. Scale bar 5 pm. (c) Cryo-TEM image of PEG-6-PCL polymersomes. Scale bar 100 nm. Reprinted from [228] with permission... 

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... 

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. 

Vesicles and liposomes are versatile supermolecular systems and possess numerous potential applications in targeting agents, microreactors, encapsulations, and drug delivery. The Rotello group developed novel recognition-mediated polymersomes... 

Polymeric vesicles, or polymersomes, are of interest for the encapsulation and delivery of active ingredients. They offer enhanced stability and lower permeability compared to lipid vesicles, and the versatility of synthetic polymer chemistry provides the ability to tune properties such as membrane thickness, surface... 

Encapsulated CPO in block copolymer polymersomes assembled from polystyrene-b-poly(L-isocyanoalanine-(2-thiophene-3-yl-ethyl)amide) The oxidation of two substrates by the encapsulated CPO was studied while the oxidation of pyrogallol was limited by diffusion into the polymersome, the rate-limiting step for the oxidation of thioansiole was the turnover by the enzyme [46]... 

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. 

So far, little work has been done to encapsulate therapeutic proteins. Hence, the encapsulation of recombinant insulin was a challenging test of therapeutic protein encapsulation in PEG-based polymersomes [241], Encapsulation of insulin in neutral and biologically stable PEG-PBD polymersomes provides a promising method to increase therapeutic efficiency by maintaining protein structure. 

Fig. 16 a-d Schematic representation of polymer nanoreactors, a Cross section of triblock copolymer vesicle, b Polymersome with encapsulated enzyme and membrane-embedded channel protein. In the case described in the text, the substrate entering the vesicle is ampicillin, and the product of the hydrolysis is ampicillinoic acid, c Polymersome with embedded ionophores allowing Ca2+ ions to enter the vesicle ere they react with phosphate ions to form calcium phosphate crystals, d The LamB protein serves as a receptor to the 1 phage virus which can inject its DNA through the channel into the polymersome [259]. Reproduced with permission of The Royal Society of Chemistry... 

Principally, encapsulation of proteins within the aqueous lumen of polymersomes can benefit from the extended circulation kinetics and controlled release properties of polymersomes. Neutral diblock (PEO-PDB, PEO-PEE), charged triblock (PEO-... 

Meng F, Engbers GHM, Feijen J. Biodegradable polymersomes as a basis for artificial cells encapsulation, release and targeting. J Control Release 2005 101 187 198. 

Polymersomes A Synthetic Biological Approach to Encapsulation and Delivery... 

The ability to encapsulate large aqueous volumes and consequently whatever is dissolved in it is one prerogative of polymersomes and represents their most promising ability. Nevertheless, while for hydrophobic and amphiphilic molecules the encapsulation process is more or less straightforward, the complex kinetics of polymersomes formations hampers the encapsulation of hydrophilic molecules. Clearly the most important parameter to consider in encapsulating water-soluble molecules is the polymersome membrane permeability. Early work carried out by Discher and co-workers [6] showed that the water permeability of PEO-PEE polymersomes was established by measuring the reduction in polymersome swelling as a function... 

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