Osteogenic and antimicrobial nanoparticulate calcium phosphate and poly-(d,l-lactide-co-glycolide) powders for the treatment of osteomyelitis

Abstract

Development of a material for simultaneous sustained and localized delivery of antibiotics and induction of spontaneous regeneration of hard tissues affected by osteomyelitis stands for an important clinical need. In this work, a comparative analysis of the bacterial and osteoblastic cell response to two different nanoparticulate carriers of clindamycin, an antibiotic commonly prescribed in the treatment of bone infection, one composed of calcium phosphate and the other comprising poly-(D,L-lactide-co-glycolide)-coated calcium phosphate, was carried out. Three different non-cytotoxic phases of calcium phosphate, exhibiting dissolution and drug release profiles in the range of one week to two months to one year, respectively, were included in the analysis: monetite, amorphous calcium phosphate and hydroxyapatite. Spherical morphologies and narrow size distribution of both types of nanopowders were confirmed in transmission and scanning electron microscopic analyses. The antibiotic-containing powders exhibited sustained drug release contingent upon the degradation rate of the carrier. Assessment of the antibacterial performance of the antibiotic-encapsulated powders against Staphylococcus aureus, the most common pathogen isolated from infected bone, yielded satisfactory results both in broths and on blood agar plates for all the analyzed powders. In contrast, no cytotoxic behavior was detected upon the incubation of the antibiotic powders with the osteoblastic MC3T3-E1 cell line for up to three weeks. The cells were shown to engage in a close contact with the antibiotic-containing particles, irrespective of their internal or surface phase composition, polymeric or mineral. At the same time, both types of particles upregulated the expression of osteogenic markers osteocalcin, osteopontin, Runx2 and protocollagen type I, suggesting their ability to promote osteogenesis and enhance remineralization of the infected site in addition to eliminating the bacterial source of infection.

Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues

“…Coating HAp particles with bioresorbable synthetic polymers based on poly(lactic-co-glycolic acid) (PLGA) has thus produced materials suitable for filling bone defects [18,19]. Biocompatible polymeric coatings around HAp particles made possible the development of multifunctional nanoparticle systems with immobilized active pharmaceutics, including vitamins and antibiotics [20,21]. Such combinations of soft, polymeric and hard, mineral components are also thought to be the route to creating materials that would mimic the natural properties of bone [22].…”

Novel alternative therapy for spinal tuberculosis during surgery: reconstructing with anti-tuberculosis bioactivity implants

“…PDLLA/clindamycin-containing calcium phosphate powders and clindamycin/calcium phosphate nanoparticulate powders both demonstrated a good antibacterial performance against Staphylococcus aureus in vitro. However, the former exhibited longer sustained drug release than the latter accompanied with the degradation of the carriers [22]. Based on the evidence of an in vitro experiment, no cytotoxic effects have been detected within the two antibiotic-containing powders.…”

Nanomedicine for safe healing of bone trauma: Opportunities and challenges

“…The amount of antibiotic released after 3 weeks was the same for coated and uncoated HA NPs, implying that the lower initial release of the antibiotic in the presence of CS coating was the main reason for the lower antibacterial efficiency [163]. However, an earlier study demonstrated the antibacterial effectiveness of clindamycin-loaded HA NPs coated with PLGA [164]. One explanation for this discrepancy could be that alkaline residues of CS might be less effective than the acidic residues of PLGA against S .…”