Biotechnol. Appl. Biochem. (2010) 57, 25–30 (Printed in Great Britain) doi:10.1042/BA20100145 25 Effect of molecular mass of methoxypoly(ethylene glycol) activated with succinimidyl carbonate on camouﬂaging pancreatic islets Leila Barani*, Ebrahim Vasheghani-Farahani* 1 , Hamideh Aghajani Lazarjani*, Sameereh Hashemi-Najafabadi* and Fatemeh Atyabi† *Biotechnology Group, Faculty of Chemical Engineering, Tarbiat Modares University, P.O. Box 14115-143, Tehran, 1411713116, Iran, and †Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran The surface modiﬁcation of Langerhans islets by graft- ing activated poly(ethylene glycol) on to their capsules in order to prevent immune-system stimulation is a novel method in diabetes cell therapy. In the present study, mPEG [methoxypoly(ethylene glycol)] with two molecular masses of 5 and 10 kDa, activated with SC (succinimidyl carbonate), was grafted on to the surface of pancreatic islets at a polymer concentration of 22 mg/ml. It was found that PEGylated islets were viable and active, and no morphological changes on the collagen capsule of islets were observed. The amount of interleukin-2 secretion from lymphocytes co-cultured with islets PEGylated with mPEG-SC of 5 and 10 kDa was 112.12 + - 23.09 pg/ml and 172.75 + - 27.94 pg/ml respectively. Thus mPEG-SC (SC-activated mPEG) with higher molecular mass was more suitable for camouﬂaging islets from the immune system. Introduction Diabetes is a metabolic disease that affects 2–5 % of the adult population in advanced countries. It is predicted that 300 million people worldwide will have this disease in 2025 [1]. Insulin-dependent diabetes mellitus (Type 1) occurs as a result of the destruction of β -cells, which produce insulin, in pancreatic islets by the immune system, so that insulin injection is required to maintain normal blood glucose [2]. The transplantation of isolated pancreatic islets is one of the new methods to treat Type 1 diabetes mellitus, but the immune system can easily destroy host cells [3,4]. To prevent the immune rejection of transplanted islets, immune-suppression drugs are used. However, these drugs have numerous risks, such as causing the spread of cancer cells or other side effects such as hypertension, dyslipidaemia, peptic ulcers and liver and kidney injury [5]. In recent years, several kinds of polymeric and inorganic matrices and membrane devices have been used to isolate transplanted tissue from the host immune system, such as vascular perfusion devices, avascular diffusion chambers, macrocapsules and microcapsules, but several problems, such as the need for surgery for vascular perfusion devices, mass-transport limitations and cell hypoxia are associated with the utilization of these devices and have yet to be solved [6]. Surface modiﬁcation of pancreatic islets with PEG [poly(ethylene glycol)] derivatives is a new method to treat Type 1 diabetes. PEG is a biocompatible polymer that is non- toxic, non-immunogenic, non-antigenic and highly soluble in water. In this method, PEG derivatives are chemically grafted on to the collagen matrix membrane (islet capsule) [7]. It has been observed that, in PEGylated proteins, the half- life of proteins increases in circulating blood and they are stable against proteolytic digestion. Also, with respect to high chain mobility and the large excluded volume of mPEG [methoxypoly(ethylene glycol)] molecules, the PEGylated proteins can protect themselves against the host’s immune system [8–10]. The grafting of mPEG on to the islet capsules does not increase the size of the islets, and PEGylated islets can be easily transplanted by a simple portal-vein injection of islets [11]. So, transplantation of PEGylated islets could be a potential treatment method for diabetes. For PEGylation (PEG grafting) to a protein, PEG needs to be activated by converting the terminal hydroxy groups into some functional group capable of reacting with the functional groups on the protein surface. The most useful method is activating the mPEG with functional groups suitable for reaction with amine groups on lysine such as SC (succinimidyl carbonate) and active esters of PEG [7]. The aim of the present study was to determine the effect of the molecular mass of mPEG, activated by SC (mPEG-SC), on the immunological response of PEGylated pancreatic islets. So, after grafting mPEG-SC on the islet capsules, the viability and functional activity of Key words: insulin, lymphocyte, methoxypoly(ethylene glycol) (mPEG), succinimidyl carbonate-activated methoxypoly(ethylene glycol) (mPEG-SC), pancreatic islet, PEGylation. Abbreviations used: AO, Acridine Orange; FBS, fetal bovine serum; HBSS, Hanks balanced salt solution; IL-2, interleukin-2; KRBB, Krebs Ringer bicarbonate buffer; mPEG, methoxypoly(ethylene glycol); PEG, poly(ethylene glycol); PI (propidium iodide); SC, succinimidyl carbonate; mPEG-SC, SC-activated mPEG; SEM, scanning electron microscopy. 1 To whom correspondence should be addressed (email evf@modares.ac.ir). C  2010 Portland Press Limited