Increasing entrapment of peptides within poly(alkyl cyanoacrylate) nanoparticles prepared from water-in-oil microemulsions by copolymerization

Abstract

Low molecular hydrophilic actives such as peptides are typically poorly encapsulated within poly(alkyl cyanoacrylate) nanoparticles when prepared from micellar or microemulsion templates. The aim of the present study was to investigate whether the entrapment of peptides within poly(alkyl cyanoacrylate) nanoparticles could be increased by functionalizing the peptide so that it could copolymerize with the alkyl cyanoacrylate monomer. Peptide and acryloyl functionalized peptide representing the antigenic epitope of the lymphocytic choriomeningitis virus glycoprotein (LCMV 33–41) were synthesized using solid-phase peptide synthesis. Poly(alkyl cyanoacrylate) nanoparticles were prepared to encapsulate either peptide or functionalized peptide using both an aqueous micellar and a water-in-oil microemulsion polymerization template. Using the micellar template, nanoparticles could not be produced in the presence of acryloyl peptide. Rather an agglomerated mass formed on the stirrer. In contrast, nanoparticles could be prepared using both acryloyl and parent peptide using the water-in-oil microemulsion template. Encapsulation efficiency was more than twofold greater for functionalized peptide, being greater than 90%. Encapsulation efficiency of functionalized peptide was also observed to increase with increasing the amount of alkyl cyanoacrylate monomer used for polymerization. A biphasic release profile was observed for the nanoparticles entrapping the non-functionalized peptide with greater than 50% of peptide being released during the first 10 min and with around 90% being released at 6 h. In contrast, less than 10% of the total amount of acryloyl LCMV 33–41 entrapped within the nanoparticles was detected in the release media following the initial 10 min, and no further release of peptide was observed up to the termination of the release study at 360 min. The difference in entrapment and release kinetics between the parent and functionalized peptide strongly supports the presumption that most of the acryloyl peptide actually intervened in the copolymerization with alkyl cyanoacrylate monomer and was covalently bound within the nanoparticles instead of being physically entrapped or adsorbed which appeared to be the case for the parent peptide. Thus, functionalizing a peptide so that it can copolymerize with the alkyl cyanoacrylate monomer is a strategy which can be used to increase the entrapment efficiency of peptides within poly(alkyl cyanoacrylate) nanoparticles and also maintain the peptide associated with nanoparticles so that the benefits of nanoparticulate delivery can be exploited.