Nano-hydroxyapatite/β-tricalcium phosphate ceramics scaffolds loaded with cationic liposomal ceftazidime: preparation, release characteristicsin vitroand inhibition toStaphylococcus aureusbiofilms

Abstract

In the current study, nano-hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) ceramics scaffolds loaded with cationic liposomal ceftazidime (CLCs) prepared by modified reverse phase evaporation method, the investigations of their release characteristics were performed by the dissolution tests, in vitro anti-biofilm activity of the scaffolds was studied by the determination of bacterial susceptibility with ELISA. The mean particle size, zeta potential, pH and entrapment efficiency of the CLCs studied were 161.5 ± 5.37 nm, 60.60 ± 5.24 mV, 6.90 ± 0.07 and 16.57 ± 0.13%, respectively. Electron microscopic images of the samples indicated that the liposomes were well preserved in the scaffolds and that it was the CLCs rather than free ceftazidime releasing from the scaffolds. The minimal inhibitory concentrations (MICs) to Staphylococcus aureus of free ceftazidime and its liposomal formulation were 6.00 μg/mL and the release behaviors of both CLCs and free ceftazidime from scaffolds were based on the dissolution/diffusion processes, Fick's law. These results demonstrated that CLCs could inhibit remarkably the formation of S. aureus biofilm more effectively than free ceftazidime (P < 0.05). The study demonstrated that the HA/β-TCP ceramic scaffolds was such a material that could sustain release CLCs and maintain the adequate amounts of CLCs to absorb to biofilm. It provided an ideal way to inhibit bacterial biofilms for clinical practices.

Lipid and polymer nanoparticles for drug delivery to bacterial biofilms

“…Both formulations showed an initial burst release followed by a slower, sustained release of the antibiotic. [53,54] With a nano-hydroxyapatite/chitosan/konjac glucomannan scaffold containing liposomal (PC:SA:Chol) vancomycin, better inhibition of S. aureus biofilm growth was observed compared to the scaffold containing the free drug or the scaffold alone. This was attributed to sustained release of vancomycin from the liposomes.…”

Calcium Orthophosphate-Based Bioceramics

“…To conclude this part, the excellent biocompatibility of calcium orthophosphate bioceramics, its possible osteoinductivity [171,563,592,666,667,668,669,670,671,672,673,674,675,676,677,678,679,680,681,682,683,684,685] and a high affinity for drugs [72,73,74,75,889,890], proteins and cells [891] make them very functional for the tissue engineering applications. The feasible production of scaffolds with tailored structures and properties opens up a spectacular future for calcium orthophosphates [888,889,890,891,892,893,894,895,896,897]. …”

Nanoparticulate Platforms for Targeting Bone Infections: Meeting a Major Therapeutic Challenge

“…However the most common strategy has been to incorporate antibiotic-loaded liposomes into bone cements. In three studies refereeing the incorporation of antibiotic-loaded liposomes into calcium phosphate-based scaffolds, liposomes were well preserved within the microporous structure of the materials and liposomal antibiotics rather than the free form of the drugs were released [20][21][22]. In all cases, liposomal antibiotics presented a significantly higher antibiofilm activity probably due to the prolonged interaction of liposomes with the biofilms, thus resulting in their accumulation surrounding the biofilms and local release of high antibiotic concentrations.…”

“…Smaller sized liposomes showed greater activity than larger particles [21] Cationic liposomal ceftazidime incorporated into nano-HA/β-tricalcium phosphate (HA/β-TCP) scaffolds Ceftazidime Ceftazidime-loaded liposomes presented a sustained profile from the scaffolds. Better inhibition of in vitro formation of S. aureus biofilm by the liposomal formulation [22] 10.2217/nnm. 15 [28] Chitosan and quaternary ammonium chitosan derivative nanoparticles Gentamicin CS and QCS reduced the adhesion of S. aureus and S. epidermidis to PMMA bone cements, which was further improved by using CS and QCS as nanoparticles [29] PLGA nanoparticles Clarithromycin Clarithromycin-loaded PLGA nanoparticles presented higher activity against S. aureus than free drug, which is explained by physicochemical properties of nanoparticles [30] PEGylated-PLGA nanoparticles Rifampicin and azithromycin Antibiotic loaded pegylated-PLGA nanoparticles showed enhanced effect in cells infected with Chlamydia trachomatis or Chlamydophila pneumoniae, since they were able to accumulate within the Chlamydia inclusions [31] PMMA/Eudragit ® RL100 (EUD) microparticles…”