Synergistic effect of PEGylation and pentoxifylline addition on immunoprotection of pancreatic islets.

ABSTRACT

In this study, a method is proposed to reduce immunological response of immune system against Langerhans islets by PEGylation of islets combined with adjuvant therapy. For this purpose, the best composition for a mixture of succinimidyl valeric acid activated mPEG (mPEG-SVA) with different molecular weights (MWs) and for a mixture of succinimidyl carbonate activated mPEG (mPEG-SC) with different MWs was determined separately. Then, the effect of pentoxifylline (PTX) as an adjuvant drug on immunological response against PEGylated islets at best mPEG composition was studied. The extent of mPEGs reaction, the amount of interlukin-2 (IL-2) and perforin secretion, and the viability of lymphocytes and islets in homo and co-cultures in the presence of PTX at different concentrations were considered for the in vitro evaluation of the proposed method. It was found, that a mixture of mPEG-SVA with MWs of 10 and 5 kDa at a composition of 75 and 25%, respectively, was the best formulation. Also, the addition of PTX drug to co-culture medium increased the protection of PEGylated islets against immune system and a concentration of 75 µg mL-1 of PTX was suitable for islet protection with no adverse effect on immune cells.