Osteoinductivity and Antibacterial Properties of Strontium Ranelate-Loaded Poly(Lactic-co-Glycolic Acid) Microspheres With Assembled Silver and Hydroxyapatite Nanoparticles

Abstract

Bone-related infection rates are 4–64% in long open bone fractures and nearly 1% in joint-related surgeries. Treating bone infections and infection-related bone loss is very important. The present study prepared strontium ranelate (SR)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (PM) with assembled silver nanoparticles (AgNPs) and hydroxyapatite nanoparticles (HANPs) (SR-PM-Ag-HA) through a novel solid-in-oil nanosuspension (S/O/N) method to achieve osteoinductivity and antibacterial properties. We evaluated the microstructure, drug release, biocompatibility, osteoinductivity, and antibacterial activity in vitro. The microspheres showed a stable shape and size. The cumulative drug release reached a maximum of ∼90% after 22 days. All groups loaded with SR enhanced MC3T3-E1 cell proliferation to a greater degree than pure PM. The osteoinductivity behavior was investigated by ALP staining and real-time PCR of osteogenic differentiation marker genes. The antibacterial activity was evaluated using antibacterial ability and biofilm formation assays. SR-PM-Ag-HA greatly enhanced osteogenic differentiation and showed excellent antibacterial properties. These results indicated that SR-PM-Ag-HA could be biocompatible and suitable for drug delivery, osteoinduction, and antibiosis, and therefore, have potential applications in the treatment of bone-related infections and promotion of bone formation at infected sites.

Development of local strontium ranelate delivery systems and long term in vitro drug release studies in osteogenic medium

“…Recently, Mao et al . published research, where SrRan was encapsulated in poly(lactic-co-glycolic acid) microspheres in size of about 150 μm, reaching drug loading of Sr 0.92 ± 0.14 atomic concentration % 19 . Although drug release for 22 days was presented, it might be not long enough, as efficiency of SrRan has been demonstrated in long term treatment 11 .…”

On the Amazing Reactivity of the Ranelate Ion: New Applications of an Old Antiosporotic Drug

“…Strontium ranelate, an old antiosporotic drug, [1,2] remains of great interest in bone healing, [3][4][5][6] dentistry [7][8][9] and several biological applications. [10][11][12][13][14][15][16] Despite its low toxicity, the drug was discontinued by the producer after the European Medicines Agency reported a slight increase (from 1.1 to 1.7% ) in cardiovascular events involving 7000 tested patients who used placebo or strontium ranelate, respectively. For this reason, it has been recommended as a therapeutic drug [17,18] only for the treatment of severe cases of osteoporosis, for patients without cardiovascular contraindications.…”

Nanoparticles from Equine Fetal Bone Marrow-Derived Cells Enhance the Survival of Injured Chondrocytes

“…Since then, EVs including exosomes or microvesicles, which occupies a certain part of secretome, were found to be efficacious against cartilage regeneration. In particular, MSC-EVs have been effective in cartilage regeneration in a rodent model of osteoarthritis [ 18 , 20 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. Despite such success and potential uses of MSC-EVs, no attempt was made on the use of MSC-derived nanoparticles or in cartilage repair in equine species.…”