Enhancing the immunomodulatory effects of the Toll-like receptors 3 agonist poly(I:C) by conjugation with polymers

Background : Poly(I:C) is a Toll-like receptors 3 agonist, which induces potent innate immune responses, and as a consequence adaptive immunity. However, the rapid degradation of poly(I:C) influences its half-life and its adjuvant effects in preclinical and clinical uses. Aims : We aimed in this study to conjugate poly(I:C) with polyethylene glycol/poly D, L-actide-co-glycolide (PLGA/PEG) polymers as an approach for better delivery and immunomodulatory effects. Materials and Methods : Female CD1 mice were treated once with PEG/PLGA, poly(I:C)/PLGA/PEG (50 μg), poly(I:C)/ PLGA/PEG (10 μg) or PEG via intraperitoneal injection and mice were sacrificed 1 day later for complete blood count analysis and analysis of the immune cells by flow cytometry. Results : Treatment with PEG/PLGA, poly(I:C)/PLGA/PEG (50 μg), poly(I:C)/PLGA/PEG (10 μg) or PEG administration resulted in significant (P = 0.0197) increases (1.89, 1.76, 1.69, and 1.42-fold, respectively) in the absolute number of neutrophils as compared to naïve mice. Conclusion : Conjugation of poly(I:C) with polymers does not hamper its immunomodulatory effects, instead it enhances its effects on increasing the number of immune cells opening an avenue for further studies on the beneficial effects of this conjugate.