Size and pH effect on electrical and conformational behavior of poly(acrylic acid): Simulation and experiment
ABSTRACT Monte Carlo simulations, experimental titrations and fluorescence correlation spectroscopy experiments were used to investigate the conformational and electrical properties of polyacrylic acids (PAA). On the one hand, titration curves were calculated to get an insight into the role of pH on the degree of ionization and conformation of PAA chains. On the other hand, experimental potentiometric titrations of PAA were also achieved for different PAA molecular weights and compared to the calculated titration curves obtained by Monte Carlo coarse grained simulations. It was found that for a large range at intermediate PAA ionizations, a good correlation is obtained between experimental and simulations data thanks to the prominence of electrostatic interactions in this domain. The effect of ionic concentration and PAA molecular weight on the titration curves was also investigated. In order to get a better understanding of PAA conformational behavior, we also investigated PAA diffusion properties in aqueous solutions as a function of pH and ionic strength by fluorescence correlation spectroscopy (FCS), thanks to its high sensitivity to measure diffusion coefficients of tracer solutes. Good qualitative agreements were observed between experimental diffusivities and polymer properties calculated from MC simulations. It was shown that the high molecular weight PAA chains display more significant changes in diffusivity in agreement with the ionization degrees and conformational changes observed in the simulations.
- SourceAvailable from: Shubhadeep Banerjee
Dataset: Banerjee 2012 pH sensitive liposome
- European Polymer Journal. 02/2010;
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ABSTRACT: pH-responsive polymers render liposomes pH-sensitive and facilitate the intracellular release of encapsulated payload by fusing with endovascular membranes under mildly acidic conditions found inside cellular endosomes. The present study reports the use of high-molecular weight poly(styrene-co-maleic acid) (SMA), which exhibits conformational transition from a charged extended structure to an uncharged globule below its pK(1) value, to confer pH-sensitive property to liposomes. The changes in the co-polymer chain conformation resulted in destabilization of the liposomes at mildly acidic pH due to vesicle fusion and/or channel formation within the membrane bilayer, and ultimately led to the release of the encapsulated cargo. The vesicles preserved their pH-sensitivity and stability in serum unlike other polymer-based liposomes and exhibited no hemolytic activity at physiological pH. The lysis of RBCs at endosomal pH due to SMA-based liposome-induced alterations in the bilayer organization leading to spherocyte formation indicated the potential of these vesicles to mediate cytosolic delivery of bio-active molecules through endosome destabilization. The SMA-loaded liposomes exhibiting excellent cytocompatibility, efficiently delivered chemotherapeutic agent 5-Fluorouracil (5-FU) within colon cancer cells HT-29 in comparison to neat liposomes. This caused increased cellular-availability of the drug, which resulted in enhanced apoptosis and highlighted the clinical potential of SMA-based vesicles.International Journal of Pharmaceutics 08/2012; 436(1-2):786-97. · 3.99 Impact Factor