Pore size is a critical parameter for obtaining sustained protein release from electrochemically synthesized mesoporous silicon microparticles

PeerJ. 2015 Oct 6:3:e1277. doi: 10.7717/peerj.1277. eCollection 2015.

Abstract

Mesoporous silicon has become a material of high interest for drug delivery due to its outstanding internal surface area and inherent biodegradability. We have previously reported the preparation of mesoporous silicon microparticles (MS-MPs) synthesized by an advantageous electrochemical method, and showed that due to their inner structure they can adsorb proteins in amounts exceeding the mass of the carrier itself. Protein release from these MS-MPs showed low burst effect and fast delivery kinetics with complete release in a few hours. In this work, we explored if tailoring the size of the inner pores of the particles would retard the protein release process. To address this hypothesis, three new MS-MPs prototypes were prepared by electrochemical synthesis, and the resulting carriers were characterized for morphology, particle size, and pore structure. All MS-MP prototypes had 90 µm mean particle size, but depending on the current density applied for synthesis, pore size changed between 5 and 13 nm. The model protein α-chymotrypsinogen was loaded into MS-MPs by adsorption and solvent evaporation. In the subsequent release experiments, no burst release of the protein was detected for any prototype. However, prototypes with larger pores (>10 nm) reached 100% release in 24-48 h, whereas prototypes with small mesopores (<6 nm) still retained most of their cargo after 96 h. MS-MPs with ∼6 nm pores were loaded with the osteogenic factor BMP7, and sustained release of this protein for up to two weeks was achieved. In conclusion, our results confirm that tailoring pore size can modify protein release from MS-MPs, and that prototypes with potential therapeutic utility for regional delivery of osteogenic factors can be prepared by convenient techniques.

Keywords: Bone morphogenetic protein; Controlled release; Mesoporous silicon; Microparticles; Pore size; Protein delivery.

Grants and funding

This work was financed in part by Xunta de Galicia, proxectos desenvolvidos por investigadores emerxentes (EM2013/042), and Fundación Ramón Areces, XVI Concurso Nacional para la Adjudicación de Ayudas a la Investigación en Ciencias de la Vida y la Materia (CIVP16A1832). EM-Silicon acknowledges financial support from the Spanish Ministry of Economy and Competitivity (PTQ-09-01-00836) and Valencia Community (IMPIVA: IMIDTA/2010/848 and IMEXPF/2010/14). ERN acknowledges a grant from Agencia Española de Cooperación Internacional para el Desarrollo. MGF acknowledges an Isidro Parga Pondal contract from Xunta de Galicia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.