Enteric trimethyl chitosan nanoparticles containing hepatitis B surface antigen for oral delivery

Abstract

Oral vaccination is the preferred route of immunization. However, the degradative condition of the gastrointestinal tract and the higher molecular size of peptides pose major challenges in developing an effective oral vaccination system. One of the most excellent methods used in the development of oral vaccine delivery system relies on the entrapment of the antigen in polymeric nanoparticles. In this work, trimethyl chitosan (TMC) nanoparticles were fabricated using ionic gelation teqnique by interaction hydroxypropyl methylcellulose phthalate (HPMCP), a pHsensitive polymer, with TMC and the utility of the particles in the oral delivery of hepatitis B surface antigen (HBsAg) was evaluated employing solutions that simulated gastric and intestinal conditions. The particle size, morphology, zeta potential, loading capacity, loading efficiency, in vitro release behavior, structure, and morphology of nanoparticles were evaluated, and the activity of the loaded antigen was assessed. Size of the optimized TMC/HPMCP nanoparticles and that of the antigen-loaded nanoparticles were 85 nm and 158 nm, respectively. Optimum loading capacity (76.75%) and loading efficiency (86.29%) were achieved at 300 mg/mL concentration of the antigen. SEM images revealed a spherical shape as well as a smooth and near-homogenous surface of nanoparticles. Results of the in vitro release studies showed that formulation with HPMCP improved the acid stability of the TMC nanoparticles as well as their capability to preserve the loaded HBsAg from gastric destruction. The antigen showed good activity both before and after loading. The results suggest that TMC/HPMCP nanoparticles could be used in the oral delivery of HBsAg vaccine.

Design of an amphiphilic hyperbranched core/shell-type polymeric nanocarrier platform for drug delivery

“…PDI is a measure of distribution of particle size. According to the literature, PDI greater than 0.5 indicates a polydisperse system, and if PDI is closer to zero, it indicates a monodisperse system [30][31][32]. In light of the literature, our results indicate that 0.466 is a favorable particle size (PDI <0.5).…”

Chitosan/sulfated locust bean gum nanoparticles: In vitro and in vivo evaluation towards an application in oral immunization

“…Naturally, the literature does not report similar nanoparticles, as LBG is being proposed for the first time herein, but chitosan-based nanoparticles have been suggested many times regarding oral vaccination [51][52][53][54][55][56][57][58]. Occasionally, ovalbumin was the tested antigen [53], resulting in nanoparticle size around 300 nm and a strong positive zeta potential (+43 mV).…”

Nanoformulations: A Valuable Tool in the Therapy of Viral Diseases Attacking Humans and Animals

“…HBsAg-loaded trimethyl CS (TMC)/hydroxypropyl methylcellulose (hypromellose) phthalate (HPMCP) NPs with particle size of 158 nm showing loading capacity and loading efficiency of 76.75% and 86.29%, respectively, at 300 μg/mL concentration of the antigen exhibited improved acid stability and better protection of entrapped HBsAg from gastric destruction in vitro, whereby the antigen showed efficacious activity also after loading. Based on these findings it could be suggested that TMC/HPMCP NPs have potential to be applied in the oral delivery of HBsAg vaccine (Farhadian et al 2015). Ndeboko et al (2015) studied the inhibition of the replication of duck hepatitis B virus (DHBV), a reference model for human HBV infection, by peptide nucleic acid (PNA) conjugated to different cell-penetrating peptides (CPPs) and found that the PNA-CPP conjugates administered to neonatal ducklings reached the liver and inhibited DHBV replication, and in mouse model conjugation of HBV DNA vaccine to modified CS ameliorated cellular and humoral responses to plasmid-encoded antigen and plasmid DNA uptake, whereby expression could also be notably increased using gene delivery systems such as CPPmodified CS or cationic NPs.…”