Functional coatings of pH-responsive casein-based films
Abstract
Over the past few years, there has been increasing attention to the design of new drug delivery systems based on milk proteins due to their excellent functional properties. In this study, we report a new approach for preparing protein-based coating films using highly methacrylated casein as a macro-crosslinker. The films exhibited a smooth surface and an even casein distribution as evidenced by both scanning electron and atomic force microscopy, respectively. The mechanical behavior of the casein-based films could be easily tuned by controlling the degree of methacrylation of the bio-based crosslinker. The as-prepared films showed pH-dependent swelling, in which the swelling ability in alkaline medium was stronger than that at acid pH. The mechanical, swelling, rheological and release performance of the casein-based films suggest that these materials have a high potential as enteric coatings for intestinal drug delivery.
Conclusions
Novel pH-sensitive crosslinked films were prepared exploiting the ionic properties that depend on pH, originated from casein. It was evidenced that the number of methacrylic functionalities of the casein macro-crosslinker had a great influence on the microstructure and rheological properties of the film-forming dispersions. Thus, when a high degree of methacrylation was used, interparticulate crosslinking could be produced, generating large particle agglomeration and increasing the dispersion viscosity. SEM and AFM analysis revealed that the films were smooth and presented an even casein distribution on their surface. Moreover, the tensile properties of the films could be tuned by varying the functionalities of the casein macro-crosslinker, reaching a good relation between strength and elongation at break. The increase in the degree of casein methacrylation led to a reduction in the elongation capability of the materials due to an increase in the crosslinking density of the polymeric network, as demonstrated by the rheological analysis. The swelling kinetics of the films at different pH showed greater swelling in the alkaline medium in comparison to that in the acidic one. This selective swelling behavior affected the viscoelastic properties of the swollen films, and higher G’ values were reached in SGF rather than PBS, as determined by rheological measurements. The release behavior of BSA from the films showed pH-dependence, with faster delivery rates in the alkaline medium. The ability of casein-based films to form ionic pairs with a basic drug like OFL was also evaluated in different physiological fluids, finding that pH and saline composition could trigger drug release. Finally, the results demonstrated the high potential of these hybrid materials to be used as suitable enteric film-coating in oral drug delivery applications.
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