Polymers have been widely used in a variety of biomedical and clinic applications ranging from suture, urinary catheters, vascular stent and as carriers for drug delivery. A large number of synthetic polymers, such as poly(tetrafluoroethylene) (PTFE), poly(L-lactic acid) (PLLA), poly(ethylene glycol) (PEG), poly(L-glycolic acid) (PLGA), as well as their co-polymers such as PEG-PLGA have been employed for various applications. However, there are still challenges ahead, namely, the high immunogenicity of polymers can result in their neutralization and elimination and can cause long term toxicity. Further, even though “non-immunogenic” materials like PEG have become the hallmark of development of pharmaceuticals, there are detectable anti-PEG antibodies in as much as 40% of the population. In this context, carbohydrate-based polymers are generally considered low immunogenic and their biomedical application have been extensively studied. Hence, to address the challenges of polymer induced immunogenicity, we have developed sugar poly(orthoester) (SPOE) polymers, where sugar monomers are linked by locked alpha-glycosidic bond similar to the natural glycosidic linkage. The synthesis of the polymers were performed by copolymerization of a novel alkyne-functionalized glucose monomer to a non-functional glucose monomer in varying ratios to achieve random co-polymers. The co-polymerization went smoothly to give the polymers of molecular weights of MnGPC = 6.3 kDa. After conjugation with biocompatible long chain oleyl aizde , followed by deprotection of the acetate groups, an amphiphilic polymer was obtained. The polymer was further subjected to self-assembly to give the sugar-coated nanoparticles (NPs) with TEM sizes of about 30 ± 4 nm and DLS sizes of about 100 ± 16 nm. In-vitro and in-vivo studies with the NP system demonstrated very favorable cell viability, and most importantly, ultralow immunogenicity. When compared with the commonly-used NP systems, such PCL-PEG and PLA-PEG, the novel NP system exhibits much lower immunogenicity, as evaluated by the level of a series of pro-inflammatory cytokines. Thus, SPOE polymers do not cause any aberrant immune activation and hence have a huge potential in various biomedical applications.

Design and synthesis of functional sugar poly(orthoester) nanomaterials with ultra-low immunogenicity

2019 Spring National Meeting

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