The role of surface charge in the desolvation process of gelatin: implications in nanoparticle synthesis and modulation of drug release

Abstract

The process of moving hydrophobic amino acids into the core of a protein by desolvation is important in protein folding. However, a rapid and forced desolvation can lead to precipitation of proteins. Desolvation of proteins under controlled conditions generates nanoparticles – homogeneous aggregates with a narrow size distribution. The protein nanoparticles, under physiological conditions, undergo surface erosion due to the action of proteases, releasing the entrapped drug/gene. The packing density of protein nanoparticles significantly influences the release kinetics. We have investigated the desolvation process of gelatin, exploring the role of pH and desolvating agent in nanoparticle synthesis. Our results show that the desolvation process, initiated by the addition of acetone, follows distinct pathways for gelatin incubated at different pH values and results in the generation of nanoparticles with varying matrix densities. The nanoparticles synthesized with varying matrix densities show variations in drug loading and protease-dependent extra- and intracellular drug release. These results will be useful in fine-tuning the synthesis of nanoparticles with desirable drug release profiles.

Modified Desolvation Method Enables Simple One-Step Synthesis of Gelatin Nanoparticles from Different Gelatin Types with Any Bloom Values

“…Electrostatic repulsion of gelatin molecules and pH-dependent degree of molecule hydration influence both size and yield of nanoparticles as was shown by many researchers [ 22 , 29 , 54 , 55 ]. Generally, higher pH values (far away from gelatin isoelectric point) resulted in lower yields and smaller particles.…”

Synthesis, Characterization, and Functionalization of Chitosan and Gelatin Type B Nanoparticles to Develop Novel Highly Biocompatible Cell-Penetrating Agents

“…Nanomaterials with absolute surface charge below 10 mV exhibit low colloidal stability, thereby causing aggregation and faster sedimentation [21,23]. Gelatin NPs appear to have higher colloidal stability, probably because the agglomeration of type B gelatin NPs is reduced at pH values far from its isoelectric point [24]. Moreover, the number of positively charged chitosan groups might have decreased after crosslinking with TPP [25].…”

Gelatin Nanoparticles-HPMC Hybrid System for Effective Ocular Topical Administration of Antihypertensive Agents

“…In vitro release studies were also performed in media containing protease or MMP-2 at the equivalent concentrations observed on the ocular surface in glaucomatous patients suffering inflammation events [53][54][55]. According to our data, these nanoparticles were resistant to these media, being able to protect the active compound and to progressively release it even at these conditions, probably due to the high density of the crosslinked gelatin matrix [78].…”