Efficient encapsulation and release of RNA molecules from gelatin-based nanoparticles

The design of synthetic carriers for nucleic acid delivery has become a research field of increasing interest. Studies on the delivery of DNA have brought up a variety of gene delivery vehicles. Recent studies in our group have demonstrated the preparation of new gelatin-based nanoparticles for the sustainable intracellular DNA delivery. Furthermore, the more recently emerged strategy by the intracellular delivery of RNA takes benefit from existing expertise in DNA transfer. In this work, the preparation and physicochemical characterization of new nucleic acid-based particles for the sustainable RNA delivery have been demonstrated. Gelatin (either high or low gel strength) and protamine sulfate have been selected to form particles by interaction of oppositely charged compounds. Particles in the absence of RNA (binary system) and in the presence of RNA (ternary system) have been prepared. The physicochemical characterization (particle size, polydispersity index, degree of RNA entrapment and RNA binding efficiency) has been evaluated as a function of the nature of the RNA derivative (acid form, diethylaminoethanol salt or core form) from torula yeast. The pH-dependent response of nanoparticles co-incubated in buffers at defined pHs that mimic late endo-lysosomal environment has demonstrated that the nanoparticles tend to destabilize and RNA can be successfully released as a consequence of changes in the intracellular pHs. Among the different systems, gelatin B (RNA)-PS nanoparticles using RNA acid form from torula yeast has proved to be the best system, from an effective and economic point of view. (C) 2016 Elsevier B.V. All rights reserved.