PLGA-Chitosan Encapsulated IL-10 Nanoparticles Modulate Chlamydia Inflammation in Mice

Abstract

Introduction

Interleukin-10 (IL-10) is a key anti-inflammatory mediator in protecting host from over-exuberant responses to pathogens and play important roles in wound healing, autoimmunity, cancer, and homeostasis. However, its application as a therapeutic agent for biomedical applications has been limited due to its short biological half-life. Therefore, it is important to prolong the half-life of IL-10 to replace the current therapeutic application, which relies on administering large and repeated dosages. Therefore, not a cost-effective approach. Thus, studies that aim to address this type of challenges are always in need.

Methods

Recombinant IL-10 was encapsulated in biodegradable nanoparticles (Poly-(Lactic-co-Glycolic Acid) and Chitosan)) by the double emulsion method and then characterized for size, surface charge, thermal stability, cytotoxicity, in vitro release, UV–visible spectroscopy, and Fourier Transform-Infrared Spectroscopy as well as evaluated for its anti-inflammatory effects. Bioactivity of encapsulated IL-10 was evaluated in vitro using J774A.1 macrophage cell-line and in vivo using BALB/c mice. Inflammatory cytokines (IL-6 and TNF-α) were quantified from culture supernatants using specific enzyme-linked immunosorbent assay (ELISA), and significance was analyzed using ANOVA.

Results

We obtained a high 96% encapsulation efficiency with smooth encapsulated IL-10 nanoparticles of ~100–150 nm size and release from nanoparticles as measurable to 22 days. Our result demonstrated that encapsulated IL-10 was biocompatible and functional by reducing the inflammatory responses induced by LPS in macrophages. Of significance, we also proved the functionality of encapsulated IL-10 by its capacity to reduce inflammation in BALB/c mice as provoked by Chlamydia trachomatis, an inflammatory sexually transmitted infectious bacterium.

Discussion

Collectively, our results show the successful IL-10 encapsulation, slow release to prolong its biological half-life and reduce inflammatory cytokines IL-6 and TNF production in vitro and in mice. Our results serve as proof of concept to further explore the therapeutic prospective of encapsulated IL-10 for biomedical applications, including inflammatory diseases.

Keywords:

• Chlamydia
• delivery system
• chitosan
• nanoparticles
• IL-10
• inflammation

Acknowledgments

The authors acknowledge the excellent administrative assistance of Yvonne Williams and LaShaundria Lucas of CNBR, and Golden Muse (http://www.golden-muse.com/scientific-illustrations) (Figure 1 diagram). This research was supported by the National Institutes of Health under Award NIH-NIGMS-RISE (2R25GM106995-06A1), the National Science Foundation (NSF)-CREST (HRD-1241701), NSF-EiR (2200529), NSF-HBCU-RISE (HRD-1646729) and NSF-HBCU-UP (HRD1911660) grants.

Disclosure

The authors report no conflicts of interest in this work.