Gellan Gum/Pectin Beads for the Targeted Colonic Delivery of Resveratrol

Abstract

This work addresses the establishment and characterization of gellan gum:pectin (GG:P) biodegradable mucoadhesive beads intended for the colon-targeted delivery of resveratrol (RES). The impact of the polymer carrier system on the cytotoxicity and permeability of RES was evaluated. Beads of circular shape (circularity index of 0.81) with an average diameter of 914 μm, Span index of 0.29, and RES entrapment efficiency of 76% were developed. In vitro drug release demonstrated that beads were able to reduce release rates in gastric media and control release for up to 48 h at an intestinal pH of 6.8. Weibull’s model correlated better with release data and b parameter (0.79) indicated that the release process was driven by a combination of Fickian diffusion and Case II transport, indicating that both diffusion and swelling/polymer chains relaxation are processes that contribute equally to control drug release rates. Beads and isolated polymers were observed to be safe for Caco-2 and HT29-MTX intestinal cell lines. RES encapsulation into the beads allowed for an expressive reduction of drug permeation in an in vitro triple intestinal model. This feature, associated with low RES release rates in acidic media, can favor targeted drug delivery from the beads in the colon, a promising behavior to improve the local activity of RES.

Conclusions

In this work, RES was successfully encapsulated in mucoadhesive beads of GG:P ionically crosslinked with Al3+ ions, achieving a high %EE (around 75%). The system was characterized and evaluated regarding cytotoxicity and in vitro intestinal permeability using a triple co-culture cell model. Beads were circular, with an average diameter of 913 μm. FTIR analysis showed that RES must be physically entrapped within the polymer network. The system was able to reduce drug release in acidic media compared to free RES, releasing only 17.6% in a pH of 1.2, and control drug release for up to 48 h in a pH of 6.8. Release data of RES from the beads correlated better with Weibull’s model and drug transport followed Fickian diffusion and Case II transport mechanisms. Cell viability studies showed that beads did not show toxicity towards a triple co-culture cell model, and even when a discrete cytotoxic effect was observed at the highest concentration evaluated in this work, the viability results were very close to the threshold value of 70%. The encapsulation of RES allowed for a significant reduction in its permeability across a triple co-culture cell model: a favorable feature for the targeted action of RES on colonic cells. In this way, the ionically-crosslinked GG:P beads represent a promising carrier system for the control of drug release throughout the GIT and the targeting of RES to the colon for the treatment of local diseases with the potential to improve the local action of the drug for the treatment of several pathologies in this organ.