Development of Drug Loaded Nanoparticles Binding to Hydroxyapatite Based on a Bisphosphonate Modified Nonionic Surfactant

Abstract

This study aimed at development of drug loaded nanoparticles which could bind to hydroxyapatite (HA) to construct drug or growth factor releasing bone graft substitutes. To this end, the terminal hydroxyl group of a nonionic surfactant Brij 78 (polyoxyethylene (20) stearyl ether) was first modified with pamidronate (Pa). Using Pa-Brij 78 as both a surfactant and an affinity ligand to HA, three different Pa surface functionalized nanoparticles were prepared, named as solid lipid nanoparticles (Pa-SNPs), nanoemulsions (Pa-NEMs), and PLGA nanoparticles (Pa-PNPs). A model drug curcumin was successfully encapsulated in the three nanoparticles. The sizes of Pa-NEM and Pa-PNP were around 150 nm and the size of Pa-SNP was around 90 nm with polydispersity indexes (PDIs) less than 0.20. Drug encapsulation efficiencies of the three nanoparticles were all greater than 85%. Furthermore, the order of binding affinity of the nanoparticles to HA wasPa-PNP>Pa-NEM=Pa-SNP. After lyophilization, the sizes of the three nanoparticles were increased about 0.5–2.0-fold but their binding affinities to HA were almost the same as the fresh prepared nanoparticles. In conclusion, a Pa-modified Brij 78 was synthesized and used for fabrication of a series of drug loaded nanoparticles to construct drug-eluting HA-based bone graft substitutes.

Fabrication of nanoparticles for bone regeneration: new insight into applications of nanoemulsion technology

“…polyethylenes, PCL) or metallic substrates (titanium, aluminum oxide). 203 Incorporating drug-loaded NPs into bone implants aims to enhance cell-implant interactions and cellular behaviors involved in osteogenesis and osteointegration 8 or to prevent unwanted tissue response such as inflammation [16][17][18]21 or bone resorption. [24][25][26] The key advantage of drug immobilization in NPs is controlled sustained drug release due to the presence of a polymer matrix serving as a diffusion barrier for entrapped drug molecules.…”

“…[24][25][26] The key advantage of drug immobilization in NPs is controlled sustained drug release due to the presence of a polymer matrix serving as a diffusion barrier for entrapped drug molecules. 16 In contrast to direct immobilization of drugs onto the surface of bone implants (e.g. via physical adsorption or covalent conjugation), functionalization of grafts with drugeluting NPs does not require affinity between the drug and implant material and thus can be applied to much wider spectrum of bioactive agents regardless of their physicochemical properties.…”

“…7 Over the past few decades, many efforts have been devoted to improving properties of implant materials by their functionalization with nanoparticles such as osteoinductive hydroxyapatite nanocrystals resembling inorganic part of the bone or bioactive nanoparticles loaded with different types of drugs/biomolecules such as factors facilitating osteogenesis (e.g. bone morphogenetic proteins, BMPs, [8][9][10] osteopontin, 11 dexamethasone 12 ), antimicrobial (Ag, 13 CuO, 14 Se, 15 curcumin, [16][17][18] chlorhexidine 19,20 ) or anti-inflammatory agents (e.g. curcumin, [16][17][18]21 quercitrin 22,23 ) and drugs inhibiting bone resorption (e.g.…”

“…bone morphogenetic proteins, BMPs, [8][9][10] osteopontin, 11 dexamethasone 12 ), antimicrobial (Ag, 13 CuO, 14 Se, 15 curcumin, [16][17][18] chlorhexidine 19,20 ) or anti-inflammatory agents (e.g. curcumin, [16][17][18]21 quercitrin 22,23 ) and drugs inhibiting bone resorption (e.g. bisphosphonates such as alendronate [24][25][26] ).…”

“…bone morphogenetic proteins, BMPs [8][9][10] ) and drugs preventing bone resorption, [24][25][26] implant-related infections or inflammation. [16][17][18]21 Drug-loaded nanoparticles can provide controlled sustained drug release over extended periods of time 16,18,21,64 and can be easily introduced into bone defects (e.g. via injection), which may eliminate adverse side effects of drugs administered systemically and current therapeutic approaches to bone injuries based on supra-physiological doses of BMP-2.…”