The pH-induced release of hydrophilic dyes from poly(2-vinylpyridine-b-ethylene oxide) (P2VP-PEO) block copolymer vesicles is investigated. The structure of the vesicles is characterized using small-angle neutron scattering (SANS) and cryo-electron microscopy (cryo-TEM). A decrease of the pH below 5 leads to protonation and dissolution of the poly-2-vinylpyridine blocks which induces rupture and dissolution of the vesicle membrane. Details of the rupture, dissolution, and release process are studied by fluorescence video microscopy, gel electrophoresis, and high-performance ultrafiltration.
Lipid and polymer vesicles are versatile cell and membrane models and are intensely investigated with respect to biomedical applications. [1][2][3][4][5][6][7] Their use as membrane models and drug carrier systems requires a good control of their size, shape, and lamellar characteristics. Due to the inherent low solubility of vesicle-forming amphiphiles, direct dissolution in aqueous solution generally leads to large, polydisperse, and polymorphous vesicles in the micrometer size range. Subsequent transformation into small, uniform vesicles in the nanometer size range requires the application of methods that disrupt vesicle membranes by utilizing large extensional or shear forces. Here we show that nanometer-sized, unilamellar lipid and polymer vesicles with a narrow size distribution can be directly prepared using inkjet printers. Their size can be controlled via the amphiphile concentration and the cartridge type. This one-step method also allows the efficient encapsulation of predefined drug mixtures and is compatible with combinatorial and highthroughput screening technology as common well-plate formats can easily be addressed.Conventional methods for the preparation of vesicles can be categorized into the use of mechanical forces, or the use of detergents or organic solvents. Mechanical methods are based on the disruption of large multilamellar vesicles into small membrane patches that close to form small unilamellar vesicles. Mechanical methods comprise tip sonication, [8] high-pressure flow through a small capillary (french press [9,10] ) or slit, [11] or high pressure extrusion through polycarbonate membranes. [12][13][14] Another common method uses mixed micelles of lipid and suitable detergents, where, upon detergent removal, unilamellar vesicles with well-tailored sizes can be formed. [15] Water-miscible, organic lipid or block copolymer solutions have been used to prepare vesi-cles upon dilution with water. [4,5,16] For all these methods, tailoring of the vesicle size is limited or requires a multistep preparation procedure.By utilizing current inkjet technology, it is possible to prepare and load small unilamellar vesicles directly in one step. In one case, inkjet printers have been used to produce drug-loaded polymer particles by "printing" a polymer solution into water. [17] Modern inkjet printers produce droplets with volumes in the picoliter range with high reproducibility, [18] which allows vesicle formation to be controlled with good precision. The method is simple and schematically shown in Figure 1.As examples of vesicle-forming amphiphiles, we used two commercially available egg phosphatidylcholines (EPC, E80; Lipoid Co.) and two block copolymers, poly(2-vinylpyridine-b-ethyleneglycol) (P2 VP 29 -PEG 15 , P2VP 66 -PEG 46 ), of different block lengths: the subscripts indicate the degrees of polymerization. These amphiphiles have been chosen because of their good solubility in ethanol. Other water-miscible solvents (propanol, diethylene glycol, tetrahydrofuran (THF), dioxane) can be used as we...
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