Quality systems and controls for pharmaceuticals/ Sarker

xxii, 182 hal.: ill.; 21 cm

Quality systems and controls for pharmaceuticals/ Sarker

xxii, 182 hal.: ill.; 21 cm

Concentration dependent structural ordering of poloxamine 908 on polystyrene nanoparticles and their modulatory role on complement consumption

Adsorption of poloxamine 908, a tetrafunctional polyethylene oxide (PEO)-polypropylene oxide ethylenediamine block copolymer, onto the surface of monodispersed polystyrene nanoparticles (232±0.33 nm) follows a bimodal pattern. Initially, the isotherm follows a Langmuir profile with a plateau observable over a very narrow equilibrium poloxamine concentration (0.0018–0.0031 mM). The isotherm then begins to rise again, reaching a final plateau at equilibrium poloxamine concentrations above 0.0089 mM. Similarly, the profile of the adsorbed layer thickness of poloxamine on the surface of nanoparticles is bimodal. The first plateau corresponds to a thickness of 4.6±0.07 nm, which occurs over the same range of poloxamine concentrations as in the initial plateau of the adsorption isotherm. The second plateau corresponds to a thickness of 9.53±0.32nm, observable at a minimum poloxamine concentration of 0.0067 mM. By using a calculated radius of gyration of a PEO chain in poloxamine as 3.1 nm, these observations reflect dynamic changes in the arrangement of surface projected PEO chains; a mushroom-like conformation at the first plateau region of the adsorption isotherm, followed by a transition into a brush-like conformation. These conformational changes are also reflected in rheological studies; the apparent viscosity of nanoparticles in which the PEO chains are in mushroom conformation is considerably higher than particles displaying the brush conformation. Further, atomic force microscopy studies (height profile and phase lag measurements) corroborated that the proposed poloxamine concentration dependent transition of surface associated PEO chains from mushroom to brush appearance is conserved when nanoparticles are dried under ambient conditions. Finally, we compared the influence of the surface PEO characteristics on complement consumption in human serum. Our results show complement-activating nature of all poloxamine-coated nanoparticles. However, complement consumption is reduced substantially with particles bearing a minimum of 11448 poloxamine molecules on their surface, thus demonstrating the importance of PEO surface density as well as brush conformation in suppressing complement consumption. This relationship between surface characteristics of poloxamine nanoparticles and their in vivo performance is discussed

Preparation of liposomes containing small gold nanoparticles using electrostatic interactions

Abstract The development of liposome-nanoparticle colloid systems offers a versatile approach towards the manufacture of multifunctional therapeutic platforms. A strategy to encapsulate small metallic nanoparticles (<4nm) within multilamellar vesicles, effected by exploiting electrostatic interactions was investigated. Two liposome-gold nanoparticle (lipo-GNP) systems were prepared by the reverse-phase evaporation method employing cationic or anionic surface functionalised particles in combination with oppositely charged lipid compositions with subsequent post-formulation PEGylation. Structural characterisation using electron microscopy and elemental analysis revealed a regular distribution of GNPs between adjacent lipid bilayers of intact liposomes. Nanoparticle encapsulation efficacy of the two lipo-GNP systems was revealed to be significantly different (p=0.03), evaluated by comparing the ratio of measured lipid to gold concentration (loading content) determined by a colorimetric assay and atomic emission spectroscopy, respectively. It was concluded that the developed synthetic strategy is an effective approach for the preparation of liposome-nanoparticle colloids with potential to control the relative concentration of encapsulated particles to lipids by providing favourable electrostatic interactions