Red blood cell membrane-camouflaged poly(lactic-co-glycolic acid) microparticles as a potential controlled release drug delivery system for local stellate ganglion microinjection.

Abstract

The stellate ganglion (SG) is a part of the sympathetic nervous system that has important regulatory effects on several human tissues and organs in the upper body. SG block and intervention have been clinically and preclinically implemented to manage chronic pain in the upper extremities, neck, head, and upper chest as well as chronic heart failure. However, there has been very limited effort to develop and investigate polymer-based drug delivery systems for local delivery to the SG. In this study, we fabricated red blood cell (RBC) membrane-camouflaged poly(lactic-co-glycolic acid) (PLGA) (PLGAM) microparticles for use as a potential long-term controlled release system for local drug delivery. The structure, size, and surface zeta potential results indicated that the spherical PLGAM microparticles were successfully fabricated. Both PLGA and PLGAM microparticles exhibited biocompatibility with human adipose mesenchymal stem cells (ADMSC) and satellite glial cells and showed hemocompatibility. In addition, both PLGA and PLGAM displayed no significant effects on the secretion of proinflammatory cytokines by human monocyte derived macrophages in vitro. We microinjected microparticles into rat SGs and evaluated the retention time of microparticles and the effects of the microparticles on inflammation in vivo over 21 days. Subsequently, we fabricated drug-loaded PLGAM microparticles by using GW2580, a colony stimulating factor-1 receptor inhibitor, as a model drug and assessed its encapsulation efficiency, drug release profiles, biocompatibility, and anti-inflammatory effects in vitro. Our results demonstrated the potential of PLGAM microparticles for long-term controlled local drug release in the SG. STATEMENT OF SIGNIFICANCE: SG block by locally injecting therapeutics to inhibit the activity of the sympathetic nerves provides a valuable benefit to manage chronic pain and chronic heart failure. We describe the fabrication of RBC membrane-camouflaged PLGA microparticles with cytocompatibility, hemocompatibility, and low immunogenicity, and demonstrate that they can be successfully and safely microinjected into rat SGs. The microparticle retention time within SG is over 21 days without eliciting detectable inflammation. Furthermore, we incorporate a CSF-1R inhibitor as a model drug and demonstrate the capacities of long-term drug release and regulation of macrophage functions. The strategies demonstrate the feasibility to locally microinject therapeutics loaded microparticles into SGs and pave the way for further efficacy and disease treatment evaluation.