Characterising the size and shape of polyamidoamines in solution as a function of pH using neutron scattering and pulsed-gradient spin-echo NMR

Khayat, Zeena; Griffiths, Peter Charles; Grillo, Isabelle; Heenan, Richard K.; King, Stephen M.; Duncan, Ruth

doi:10.1016/j.ijpharm.2006.03.003

Cited by 26 publications

(25 citation statements)

References 39 publications

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“…1; Table 1). PAA shape, size, and pH-responsive changes in conformation were determined using small angle neutron scattering (SANS) [17,18], and the rate of diffusion in solution was defined using pulsed-gradient spin-echo NMR [17]. Most recently PAA interaction with model micelles [19], and model membranes whose composition was chosen to mimic the plasma, endosomal and lysosomal membrane was measured using surface tension and electron plasmon resonance techniques in combination with SANS [19].…”

Section: Introductionmentioning

confidence: 99%

Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo

Richardson

Pattrick

Lavignac

et al. 2010

Journal of Controlled Release

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Linear poly(amidoamine)s (PAAs) have been designed to exhibit minimal non-specific toxicity, display pHdependent membrane lysis and deliver genes and toxins in vitro. The aim of this study was to measure PAA cellular uptake using ISA1-OG (and as a reference ISA23-OG) in B16F10 cells in vitro and, by subcellular fractionation, quantitate intracellular trafficking of 125 I-labelled ISA1-tyr in liver cells after intravenous (i.v.) administration to rats. The effect of time after administration (0.5-3 h) and ISA1 dose (0.04-100 mg/kg) on trafficking, and vesicle permeabilisation (N-acetyl-b-D-glucosaminidase (NAG) release from an isolated vesicular fraction) were also studied. ISA1-OG displayed~60-fold greater B16F10 cell uptake than ISA23-OG. Passage of ISA1 along the liver cell endocytic pathway caused a transient decrease in vesicle buoyant density (also visible by TEM). Increasing ISA1 dose from 10 mg/kg to 100 mg/kg increased both radioactivity and NAG levels in the cytosolic fraction (5-10 fold) at 1 h. Moreover, internalised ISA1 provoked NAG release from an isolated vesicular fraction in a dose-dependent manner. These results provide direct evidence, for the first time, of PAA permeabilisation of endocytic vesicular membranes in vivo, and they have important implications for potential efficacy/toxicity of such polymeric vectors.

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Section: Introductionmentioning

confidence: 99%

Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo

Richardson

Pattrick

Lavignac

et al. 2010

Journal of Controlled Release

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“…[5,[7][8][9] Techniques more commonly applied in colloidal science such as pulsed-gradient spin-echo NMR, electron paramagnetic resonance (EPR) and small-angle neutron scattering (SANS) were used to study solution conformation and model surface interaction. Initial studies on the solution behavior of ISA23 Á HCl indicated a Gaussian-coil conformation with pH-induced coil expansion.…”

Section: Introductionmentioning

confidence: 99%

“…Initial studies on the solution behavior of ISA23 Á HCl indicated a Gaussian-coil conformation with pH-induced coil expansion. [7,8] At higher pH values, including pH ¼ 7.4, the polymer is negatively charged and adopts a rather compact structure (R g % 2 nm) but as the pH decreases the ISA23 radius of gyration increases to a maximum (R g % 8 nm) before coil collapse at very low pH (%3). These results supported the proposed mode of action of ISA23, namely a coil expansion on passing from the extracellular neutral pH to the acidic pH encountered in the endosomal and lysosomal compartments with consequent membrane interaction and permeabilization.…”

Section: Introductionmentioning

confidence: 99%

Interaction of an Endosomolytic Polyamidoamine ISA23 with Vesicles Mimicking Intracellular Membranes: A SANS/EPR Study

Griffiths

Nilmini

Carter

et al. 2010

Macromolecular Bioscience

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The mechanism of ISA23 · HCl interaction with model membrane vesicles (80-100 nm in diameter) was investigated using EPR in conjunction with SANS. For EPR, 16-DSE was dissolved in the vesicle membrane to measure its dynamics and polarity, whereas a spin-labeled (Tempo)-ISA 23 analogue was used to give a measure of the polymer flexibility. When ISA23 was added to the external vesicle surface, no interaction was found. This observation conflicts with the reported ability to lyse RBC, but is in agreement with recent studies that showed no effect on membrane permeability when a PAA was added to an incubation medium containing isolated lysosomal vesicles. The vesicle-mimetic models used here provide a new and useful tool for studying endosomolytic polymer/membrane interactions.

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“…Thus, this thermo-responsive property has been utilized as an ''on-off" switch for drug release, attachment/detachment of cells, and so on [16][17][18][19]. Besides, pH is another important stimulus, which has been used to develop pH-responsive materials [4,20,21]. Weakly acidic or alkalescent polymers containing carboxylic acid or amine are the pH-responsive candidates that undergo a change in the ionization state on the variation of pH values, resulting in a reversible change between hydrophilicity and hydrophobicity.…”

Section: Introductionmentioning

confidence: 99%