(203e) Recognitive Methacrylated Alginate Nanoparticles for Protein Therapeutics

One of the main foci in biomaterial design is the development of novel approaches to specifically recognize biological cues and deliver therapeutics in a targeted mechanism. A variety of recognition molecules have been used to improve protein and drug delivery (e.g. antibodies, carbohydrates, peptides). However, these biomolecules are fragile, temperature and pH sensitive, and highly expensive, thus limiting their application worldwide. An alternative to these, are molecularly imprinted polymers (MIPs), which are biomaterials that recognize a predetermined template (e.g. proteins, small molecules). These systems are synthesized by crosslinking a polymeric matrix around the desired biomarker, therefore creating nanocavities that have complementary physicochemical characteristics to the template.¹ Among these systems are alginate particles, which have been previously used as drug and protein delivery vehicles.^[2 Alginates are biocompatible anionic biopolymers, that can be ionically or chemically crosslinked, offering a wide variety of biochemical and physical characteristics.

 

The work presented herein was developed to provide insights on the protein/carrier interactions, and the importance that surface charge, chemical, and mechanical properties have on the recognition of proteins by molecularly imprinted natural polymers. Sodium alginate was functionalized with different methacrylate molecules (e.g. benzyl methacrylate, 2-hydroxyethyl methacrylate) using a carbodiimide reaction. Successful functionalization of the alginate was confirmed via Fourier transform infrared spectroscopy and NMR spectroscopy. Alginate nanoparticles were synthesized using water/oil microemulsions. Briefly, functionalized-alginate solution (up to 30% (v/v)) was emulsified in toluene with the biomolecular template, 1% (w/w) dioctyl sodium sulfosuccinate as a surfactant, and 1% (w/w) Irgacure 184 as photoinitiator. Nanoparticle solution was crosslinked for 10 min using a 140 mW/cm² UV point-source. Resulting nanoparticles were purified and the template remains were removed by intensive washing steps. Physical characterization of the obtained particles was performed using light and electron microscopy, dynamic light scattering and zeta potential measurements confirming the morphology and charge of the functionalized alginate nanoparticles. Furthermore, the ability of these nanoformulations to recognize their template was evaluated using re-binding studies. Proteins similar to charge and size to the template used, were similarly recognized by functionalized alginate nanoparticles. However, by changing the functionalization molecule, it was shown that the physicochemical characteristics of alginate MIPs affected considerably their binding and recognition. These results exhibit the ability of molecular recognitive natural polymeric systems, such as alginate nanoparticles, to be tailored and enhance their specificity to be used as drug and protein delivery carriers.

 

[1] Peppas NA, Huang Y. Polymers and gels as molecular recognition agents. Pharmaceutical research. 2002;19:578-87.

[2] Lee KY, Mooney DJ. Alginate: properties and biomedical applications. Prog Polym Sci. 2012;37:106-26.