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Tetracycline nanoparticles loaded calcium sulfate composite beads for periodontal management
Authors:N Sindhura Reddy  S Sowmya  Joel D Bumgardner  KP Chennazhi  Raja Biswas  R Jayakumar
Affiliation:1. Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India;2. Biomedical Engineering Department, University of Memphis, Joint University of Memphis–University of Tennessee Graduate Biomedical Engineering Program, Memphis, TN, USA
Abstract:

Background

The objective of this study was to fabricate, characterize and evaluate in vitro, an injectable calcium sulfate bone cement beads loaded with an antibiotic nanoformulation, capable of delivering antibiotic locally for the treatment of periodontal disease.

Methods

Tetracycline nanoparticles (Tet NPs) were prepared using an ionic gelation method and characterized using DLS, SEM, and FTIR to determine size, morphology, stability and chemical interaction of the drug with the polymer. Further, calcium sulfate (CaSO4) control and CaSO4-Tet NP composite beads were prepared and characterized using SEM, FTIR and XRD. The drug release pattern, material properties and antibacterial activity were evaluated. In addition, protein adsorption, cytocompatibility and alkaline phosphatase activity of the CaSO4-Tet NP composite beads in comparison to the CaSO4 control were analyzed.

Results

Tet NPs showed a size range of 130 ± 20 nm and the entrapment efficiency calculated was 89%. The composite beads showed sustained drug release pattern. Further the drug release data was fitted into various kinetic models wherein the Higuchi model showed higher correlation value (R2 = 0.9279) as compared to other kinetic models. The composite beads showed antibacterial activity against Staphylococcus aureus and Escherichia coli. The presence of Tet NPs in the composite bead didn't alter its cytocompatibility. In addition, the composite beads enhanced the ALP activity of hPDL cells.

Conclusions

The antibacterial and cytocompatible CaSO4-Tet NP composite beads could be beneficial in periodontal management to reduce the bacterial load at the infection site.

General significance

Tet NPs would deliver antibiotic locally at the infection site and the calcium sulfate cement, would itself facilitate tissue regeneration.
Keywords:ALP  alkaline phosphatase  BCA  bicinchoninic acid  O-CMC  O-carboxymethyl chitosan  CaCl2  calcium chloride  CaSO4  calcium sulfate  CaSO4·  1/2H2O  calcium sulfate hemihydrate  CFU  colony forming units  DAPI  4&prime    6-diamidino-2-phenylindole  DD  degree of deacetylation  DLS  dynamic light scattering  E  coli  Escherichia coli  EthD-1  ethidium homodimer-1  EtO  ethylene oxide gas  FBS  fetal bovine serum  FTIR  Fourier transform infrared spectroscopy  HAp  hydroxyapatite  hPDL  human periodontal ligament cells  L  B  broth  Luria Bertani broth  MEM  minimal essential media  NPs  nanoparticles  PBS  phosphate buffered saline  Pen&ndash  Strep  penicillin&ndash  streptomycin  PNPP  p-nitrophenylphosphate  K2SO4  potassium sulfate  SEM  scanning electron microscope  S  aureus  Staphylococcus aureus  Tet  tetracycline hydrochloride  XRD  X-ray diffraction
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