Development of a PHBV nanoparticle as a peptide vehicle for NOD1 activation

Abstract

NOD1 is an intracellular receptor that, when activated, induces gene expression of pro-inflammatory factors promoting macrophages and neutrophils recruitment at the infection site. However, iE-DAP, the dipeptide agonist that promotes this receptor's activation, cannot permeate cell membranes. To develop a nanocarrier capable of achieving a high and prolonged activation over time, iE-DAP was encapsulated in nanoparticles (NPs) made of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). The physicochemical properties, colloidal stability, encapsulation efficiency, and cellular uptake of iE-DAP-loaded PHVB NPs were analyzed. Results evidenced that physicochemical properties of iE-DAP-loaded NPs remained stable over time, and NPs were efficiently internalized into cells, a process that depends on time and concentration. Moreover, our results showed that NPs elicited a controlled cargo release in vitro , and the encapsulated agonist response was higher than its free form, suggesting the possibility of activating intracellular receptors triggering an immune response through the release of NOD1 agonist.

Copolymers and Blends Based on 3-Hydroxybutyrate and 3-Hydroxyvalerate Units

“…The research developed by Cabaña-Brunod et al [126] has found that PHBV nanoparticles (NPs) could be effectively used as a delivery system for iE-DAP, a NOD1 (intracellular receptor) agonist. The NPs showed controlled release of iE-DAP in-vitro, and the response of the encapsulated agonist was found to be higher than its free form.…”

Nanocarriers for effective delivery: modulation of innate immunity for the management of infections and the associated complications

“…Further studies also indicate that intradermal and nasal administration of MDP-encapsulated N-trimethyl chitosan nanoparticles could increase the immunogenicity of antigens [233]. In a separate study, Mauricio et al developed an iE-DAP-loaded biocompatible poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticle, and found that the nanoparticle could be taken up by cells effectively [238]. Intriguingly, this nanoparticle enables a sustained and controlled release of cargo.…”

Enhancing Targeted Therapy in Hepatocellular Carcinoma through a pH-Responsive Delivery System: Folic Acid-Modified Polydopamine-Paclitaxel-Loaded Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Nanoparticles

“…Carbohydrate polymers have been recognized for their favorable characteristics, including good biocompatibility, inherent nontoxicity, and biodegradability. , Among these polymers, poly­(3-hydroxybutyrate- co -3-hydroxyvalerate) (PHBV) stands out as a biodegradable biopolymer derived from starch through fermentation engineering technology . Notably, PHBV has demonstrated its ability to form polymeric NPs that can encapsulate compounds and regulate their release. − Compared to other polymers like poly­(lactic- co -glycolic acid) (PLGA), PHBV exhibits advantages such as biodegradability, nontoxicity, and low production cost . Furthermore, PHBV NPs have exhibited effective control over the release rate of encapsulated drugs, making them a promising candidate for drug delivery systems that respond to the tumor microenvironment …”