Polyacrylic acids (PAA) are a well-established class of polymers for mucoadhesives of drug delivery systems. The most widely used derivatives of acrylic acid are Carbopol 934P and its sodium salt [74]. At low pH, PAA forms colloidal dispersions of low viscosity, however, following neutralization with a suitable inorganic or organic base, highly viscous gels are produced due to the repulsion of the ionized carboxylic acid groups [75]. Peppas et al. were the first to explain the mucoadhesive behavior of acrylic acid on the basis of interdiffusion theory. They suggested that an increase in chain interpenetration directly enhance the mucoadhesion. Jabbari et al. used ATR/FTIR for mucin interpenetration at the polyacrylic acid/mucin interface [76], which was later confirmed by Clausen et al. through permeation enhancement of fluoresceinisothiocyana (FITC)-labeled drugs [77].
Polycarbophil is acrylic acid derivative that is insoluble in the aqueous medium but at the same time highly swellable as well as mucoadhesive. There are several varieties of this particular polymer depending upon the molecular weight, type, and degree of cross-linking and the molecular architecture. On the basis of these features, these polymers have variable mucoadhesive performance [78]. Polyacrylic acid is widely used to form mucoadhesive films, tablets, hydrogels, and for the formation of nanoparticulate drug delivery systems.
PAA-coated Fe3O4 NPs have been prepared by coprecipitation of Fe2+ and Fe3+ salts, following the Massart method (1981). Initially, in a typical synthesis, 24.3 g of FeCl3·6H2O and 16.7 g of FeSO4·7H2O (molar ratio Fe3+/Fe2+ of 1.5) are placed in a 500 mL round-bottom flask and dissolved in 200 mL of 0.01 M HCl solution with mechanical stirring. Temperature is increased to 60°C, and 60 mL of ammonia solution (28%) is added to the mixture, observing the immediate formation of black magnetite NPs. Secondly, 3.9 g of PAA is added 30 s after the addition of the ammonia solution and the reaction is allowed to continue for 1 h. After cooling down to room temperature, pH is acidified to 4 by the addition of HCl (9% wt). Finally, the mNPs are magnetically separated and washed four times with deionized water and finally redispersed in water.
The precipitates formed in the presence of the kosmotropic salt are readily resuspended at high protein concentration in a variety of standard affinity or ion exchange column loading buffers [54]. Ideally, the next step might be filtration on a Q membrane or AEX hybrid filter such as Emphaze. The relatively low MW of the PAA reduces its effects on solution viscosity and also makes it easier to clear residual PAA. Follow-on use of Protein A or CEX or mixed-mode (e.g., Capto ImpRes MMC) would allow for flow-through of residual polymer. Protein A affinity chromatograpy would also be an option as it appears particularly good at clearing precipitating polymers (e.g., [36]).
