Validation of silica-collagen nanocomposite for prolonged growth hormone delivery

Abstract

Pharmacological treatments with growth hormone (GH) in short stature syndromes require daily injections and therefore new formulations are needed. In this context, we have analyzed how surface modifications of silica nanoparticles (SiNP) allow loading of GH to be tested as a prolonged hormone delivery system in a mouse model (neuroDrd2KO) in which continuous GH secretion feminizes hepatic gene expression. We previously demonstrated that unmodified SiNP offer a GH higher adsorption capacity (12 ng GH/ng SiNP) compared to chemically modified (–NH2, –SH, isobutyl) SiNP. These GH-loaded SiNP showed a progressive GH release profile reaching 0.3 ng GH/ng SiNP after 5 days. In the present work we sought to validate GH release kinetics from two delivery systems: GH-loaded SiNP-collagen nanocomposite (GH@SiNP@collagen) and GH-loaded on collagen matrix (GH@collagen) were tested as prolonged GH delivery systems. To that end, 200 nm-diameter SiNP were prepared following the Stöber method and maximum GH adsorption was allowed by incubation with hormone for 24 h. To prepare GH@SiNP@collagen, GH-loaded SiNP were incorporated in a collagen matrix during its preparation. GH was also incorporated in a collagen matrix to prepare the GH@collagen system. Determination of GH release was assessed for up to 5 days by monitoring the hormone concentration in exposed media by RIA. Both systems showed a progressive GH release profile. GH@SiNP@collagen released 40% of GH loaded on SiNP reaching 0.1 ng GH/ng SiNP after 5 days. On the other hand, GH@collagen released 100% of loaded GH reaching 2.4 ng GH/ng SiNP after the same time period. These results indicate that GH@SiNP@collagen can be used to provide a prolonged GH delivery and that this nanocomposite is adequate to be tested on the dwarf neuroDrd2KO mouse model.