Polymersome

Recently, unique vesicle-forming (spherical bUayers that offer a hydrophilic reservoir, suitable for incorporation of water-soluble molecules, as well as hydrophobic wall that protects the loaded molecules from the external solution) setf-assembUng peptide-based amphiphilic block copolymers that mimic biological membranes have attracted great interest as polymersomes or functional polymersomes due to their new and promising applications in dmg delivery and artificial cells [ 122]. However, in all the cases the block copolymers formed are chemically dispersed and are often contaminated with homopolymer. 

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. 

Upadhyay KK, Bhatt AN, Mishra AK, Dwarakanath BS, Jain S, Schatz C, Le Meins JE, Earooque A, Chandraiah G, Jain AK, Misra A, Lecommandoux S (2010) The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(y-benzyl L-glutamate)-b-hyaluronan polymersomes. Biomaterials 31(10) 2882... 

The vesicles made from lipid bilayers are analogous to polymersomes, which are vesicles formed from high molecular weight amphiphilic block copolymers [94—96], Unlike the micelles discussed earlier from the similar copolymer components, the presence of bilayer walls formed from the aggregation of hydrophobic domains provides new properties. They can be designed to respond, for example, by opening or by disassembly, to external stimuli such as pH, heat, light, and redox processes [97]. This makes them usable as scaffolds for cascade reactions, even those with combinations of enzymes [98, 99]. 

Letchford K, Burt H (2007) A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures micelles, nanospheres, nanocapsules and polymersomes. Eur J Pharm Biopharm 65 259-269... 

Recently, biodegradable polymers have been used to fabricate macro- and nanometer scale self-assembled systems such as microspheres (MSs), nanospheres (NSs), polymer micelles, nanogels, and polymersomes (Fig. 1). These have attracted growing interest because of their potential utility for drug delivery systems (DDS), tissue engineering, and other applications. To construct these self-assembled systems... 

Fig. 1 Typical examples of nanometer-scale polymeric assemblies polymer micelles, polymersomes,...

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... 

Fig. 11 Drug loading, release, and antitumor activity of biodegradable polymersomes.

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. 

Kimura and coworkers have also developed hybrid-type polymersomes composed of polysarcosine-b-PLA ( lactosomes ) [242-243]. The lactosomes are fully biodegradable due to the equipped metabolic pathway for sarcosine and lactic acid. Hence, the lactosome is preferred for in vivo applications rather than for in vitro studies. Indeed, they have demonstrated a potential utility of lactosomes as a contrast agent for in vivo liver tumor imaging [243]. Lactosomes labeled with indocyanine green showed high escape ability from RES, were found to be stable in... 

Riva R, l azzari W, Billiet L, Du Prez F, Jerome C, Lecomte P (2011) Fheparation of pH-sensitive star-shaped aliphatic poplyesters as precursors of polymersomes. J Polym Sci A Polym Chem 49 1552-1563... 

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... 

Uzun O, Xu H, Jeoung E, Thibault RJ, Rotello VM. Recognition-induced polymersomes structure and mechanism of formation. Chem Eur J 2005 11 6916-6920. 

Block Copolymers are macromolecules which are composed of blocks usually in linear as it shown in Fig. 3.20, where it is illustrated a classical block copolymer. Main block copolymers are amphiphilic block copolymers having united hydrophilic blocks to hydrophobic blocks. Amphiphilic block copolymer have surfactant properties and form different kinds of associations, such as micelles, nanospheres, nanocapsules and polymersomes This tipe of association can act like excellent vehicles of several active principles. The composition, aggregate formation and the different applications of these materials have been reviewed [112], Figure 3.20 also illustrates the nanoparticulate drug delivery systems formed by amphiphilic block copolymers and their general characteristics. 

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