Efficacy studies on diblock copolymers for immunoprotective alginate-based microcapsules

The studies presented in this thesis were aimed at overcoming the issues of reproducing the encapsulation procedure and the extreme lab-to-lab variations that hamper its widespread application. First it was shown that small variations in composition of the alginate gel have a tremendous effect on the immune response. Furthermore, the obstacles of the encapsulation procedure could be overcome by applying a masking layer of diblock copolymers on the surface of the capsules. To this end, different PEG-b-PLL and PNIPAAm(-PAAm)-b-PLL copolymers were adsorbed to the alginate gels and the binding process was studied through fluorescence labeling of the PEG blocks, as well as by Fourier infrared spectroscopy and atomic force microscopy. Fluorescence labeling studies showed a certain length of blocks was required to provide integral stability of the capsules. Saturation of the capsule’s surface with the diblock copolymers was achieved after 30-60 minutes. This was also sufficient to provide adequate immunoprotection and mechanical stability, yet the PEG-b-PLL-alginate capsules caused a strong inflammatory reaction in the in-vivo studies. The FTIR results revealed that longer incubation times of 50 hours were required to achieve surface saturation. Contrary to the fluorescence labeling study, both FTIR and AFM results revealed the penetration of copolymers into the alginate gel. The introduction of the PLL pretreatment reduced the penetration and a better surface coverage was achieved. This was also corroborated by the high retrieval rates and low capsular overgrowth. These results demonstrate the applicability of the PEG-b-PLL copolymers as anti-biofouling layer on the alginate-PLL surface.