Preparation of emulsifying wax/glyceryl monooleate nanoparticles and evaluation as a delivery system for repurposing simvastatin in bone regeneration.

Preparation of emulsifying wax/glyceryl monooleate nanoparticles and evaluation as a delivery system for repurposing simvastatin in bone regeneration.

Eskinazi-Budge Aaron; Manickavasagam Dharani; Czech Tori; Novak Kimberly; Kunzler James; Oyewumi Moses O

Drug development and industrial pharmacy

2018

2018-10

Simvastatin (Sim) is a widely known drug in the treatment of hyperlipidemia, which has attracted so much attention in bone regeneration due to its potential osteoanabolic effect. However, repurposing of Sim in bone regeneration will require suitable delivery systems that can negate undesirable off-target/side effects. In this study, we have investigated a new lipid nanoparticle (NP) platform that was fabricated using a binary blend of emulsifying wax (Ewax) and glyceryl monooleate (GMO). Using the binary matrix materials, NPs loaded with Sim (0-500 microg/mL) were prepared and showed an average particle size of about 150 nm. NP size stability was dependent on Sim concentration loaded in NPs. The suitability of NPs prepared with the binary matrix materials in Sim delivery for potential application in bone regeneration was supported by biocompatibility in pre-osteoclastic and pre-osteoblastic cells. Additional data demonstrated that biofunctional Sim was released from NPs that facilitated differentiation of osteoblasts (cells that form bones) while inhibiting differentiation of osteoclasts (cells that resorb bones). The overall work demonstrated the preparation of NPs from Ewax/GMO blends and characterization to ascertain potential suitability in Sim delivery for bone regeneration. Additional studies on osteoblast and osteoclast functions are warranted to fully evaluate the efficacy of Sim-loaded Ewax/GMO NPs using in-vitro and in-vivo approaches.

Animals; bone; Bone Regeneration/*drug effects/physiology; drug delivery; Drug Delivery Systems/*methods; Drug Evaluation; Drug Repositioning/methods; Emulsifying Agents/administration & dosage/*chemical synthesis; Glycerides/administration & dosage/*chemical synthesis; Mice; nanoemulsions; nanoparticles; Nanoparticles/administration & dosage/*chemistry; osteoblasts; Osteoblasts/drug effects/physiology; Osteoclasts; Preclinical/methods; RAW 264.7 Cells; Simvastatin/administration & dosage/*chemical synthesis; Waxes/chemical synthesis/pharmacology

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

1583–1590

10

44