Polymersomes loading

Fig. 12 Shown on the left is a cut through an initial configuration of a vesicle loaded with polymer chains. The hydrophobic and hydrophilic segments of the amphiphile and the hydrophilic beads of the polymer load are shown in red, green, and blue, respectively. Three characteristic snapshots of a rupturing polymersome, loaded with nh = 10 long hydrophilic polymers are shown on the right...

Ahmed F, Pakunlu RI, Brannan A, Bates F, Minko T, Discher DE (2006) Biodegradable polymersomes loaded with both paclitaxel and doxorubicin permeate and shrink tumors, inducing apoptosis in proportion to accumulated drug. J Contr Release 116 150-158... 

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. 

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... 

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

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. 

To bring the nanocontainer to a specific place where it should release its pay-load, targeting is a required approach. Hence, much work has been carried out to attach ligands or antibodies to the hydroxyl end-group of PEG-based assemblies [150,181,243], Biotinylated nondegradable block copolymer assemblies have been shown to attach to surfaces coated with the biotin receptor avidin [146,147, 150,244], Coupling chemistry has been applied to conjugate either an antihuman IgG, or antihuman serum to PEG-carbonate- or PEG-polyester-assembled polymer vesicles [149,245], HIV-derived Tat peptide attached to PEG-PBD polymersomes enhanced the cellular delivery of nanoparticles [246] and increased dendritic cell uptake in vitro [181]. 

Fig. 3 Left Schematic representation of a DNA-loaded triblock-based polymersome. The virus, a X phage, binds a LamB protein and the DNA is transferred across the block copolymer membrane. Right An electron micrograph of negatively stained complexes formed between X phage and vesicles bearing LamB proteins at 37° C. The X phage (large structure on the top left comer) is attached to one vesicle via its tail. Ref. [27]. Copyright (2002) National Academy of Sciences, U.S.A...

For the example application of a loaded polymersome, we require Xnab 30.5. The determination of the coefficients of the hydrophilic moieties is motivated by reproducing for them good solvent conditions. In the following, we set all the third order virial coefficients between the hydrophilic units to zero. The second order coefficients should have a positive value, which in the case of the B monomers determines the size of the hydrophilic head of the amphiphile. The coefficient vbb has to be empirically determined to comply with the bilayer stability (e.g., large values of vbb gives rise to micelle formation instead of bilayers). In this work, we use vbb = vqc = 0.1. Substitution of vbb and into (17) yields vMi = -6. Table 1 summarizes the values of the virial coefficients used to study the loaded polymer-somes. 

Ahmed F, Pakunlu RI, Srinivas G, et al. Shrinkage of a rapidly growing tumor by drug-loaded polymersomes pH-triggered release through copolymer degradation. Mol Pharm 2006 3 340-350. 

Normally the water-soluble drug is added during the hydration process and subsequently the loaded polymersomes are purified by the original solution by either dialysis or size exclusion chromatography [68]. However, this method ensures relative high encapsulation efficiency only if combined with post processing by extrusion or sonication [51,112]. Interaction between copolymers and the desired molecules certainly favours the efficiency. pH sensitive systems such as PMPC-PDPA showed efficient encapsulation efficiency due to the strong interaction between the polymers and the DNA prior to pH variation [51,70,113]. 

Upadhyay KK, Meins J-FL, Misra A, Voisin P, Bouchaud V, Ibaiboure E, Schatz C, Lecommandoux S (2009) Biomimetic doxorabicin loaded polymersomes from hyaluronan-block-poly(benzyl glutamate) copolymers. Biomacromolecules 10(10) 2802—2808... 

Ghoroghchian PP, Frail PR, Susumu K, Park TH, WU SP, Uyeda HT, Hammer DA, Therien MJ (2005) Broad spectral domain fluorescence wavelength modification of visible and near-infrared emissive polymersomes. J Am Chem Soc 127 15388-15390 Ghoroghchian PP, Jin JJ, Brannan AK, Frail PR, Bates FS, Therien MJ, Hammer DA (2006) Quantitative membrane loading of polymer vesicles. Soft Matter 2 973-980 Pata V, Ahmed F, Discher DD, Dan N (2004) Membrane solubilization by detergent resistance conferred by thickness. Langmuir 20(10) 3888-3893... 

In Chapter 4, Massignani, Lomas and Battaglia review the fabrication processes used to form polymersomes, membrane-enclosed structures that are formed through self-assembly of amphiphilic copolymers. The resulting molecular properties, methods to control their size, loading strategies and applications of polymersomes are also detailed. 

---