Dentin remineralizing ability and enhanced antibacterial activity of strontium and hydroxyl ion co-releasing radiopaque hydroxyapatite cement.

Dental caries is an infection of the mineralized tooth structures that advances when acid secreted by bacterial action on dietary carbohydrates diffuses and dissolves the tooth mineral leading to demineralization. During treatment, clinicians often remove only the superficial infected tooth structures and retain a part of affected carious dentin to prevent excessive dentin loss and pulp exposure. Calcium hydroxide is used to treat the affected dentin because it is alkaline, induces pulp-dentin remineralization and decreases bacterial infection. Presence of strontium ions has also been reported to exhibit anticariogenic activity, and promote enamel and dentin remineralization. The objective of the present study was to develop novel hydroxyapatite cement from tetracalcium phosphate which gradually releases hydroxyl and strontium ions to exhibit antibacterial activity. Its potential to remineralize the dentin sections collected from extracted human molar tooth was studied in detail. The pH of all the experimental cements exhibited a gradual increase to ~10.5 in 10 days with 10% strontium substituted tetracalcium phosphate cement (10SC) showing the highest pH value which was sustained for 6 weeks. 10SC showed better antibacterial property against S. aureus and E. coli at the end of 1 week compared to other cements studied. It also exhibited the highest radiopacity equivalent to 4.8 mm of Al standard. 10SC treated dentin section showed better remineralization ability and highest elastic modulus. We can conclude that the hydroxyl and strontium ions releasing tetracalcium phosphate cement exhibits good antibacterial property, radiopacity and has the potential to encourage dentin remineralization.

Curcumin Releasing Eggshell Derived Carbonated Apatite Nanocarriers for Combined Anti-Cancer, Anti-Inflammatory and Bone Regenerative Therapy.

Bone cancer or osteosarcoma is an aggressive cancer affecting the long bones and is treated by a combination of surgery and chemotherapy. Local drug delivery directly to the site of bone cancer and the use of plant-based drugs has been explored towards improving the efficacy and decreasing the toxicity of the anti-cancer drugs. Curcumin, derived from turmeric is highly effective against cancer cells and shows very low toxicity against normal cells. Bone repair is facilitated by use of bone substitutes such as bioceramics, amongst which the carbonated apatite (CA) nanocarriers closely mimic the natural bone mineral. In the current work, we have developed CA nanocarriers based local delivery of curcumin as an adjunct treatment for bone cancer. CA nanocarriers with 6 wt.% carbonate were prepared by wet chemical synthesis using synthetic derived (6SWCA) and eggshell derived (6EWCA) precursors along with hydroxyapatite (WHA) as a control. The X-ray diffraction (XRD) patterns showed the CAs to be phase pure with a mean crystallite size of 17 nm. The Fouriertransform infrared spectroscopy (FTIR) analysis of both CAs indicated the carbonate substitution as B-Type. The amount of carbonate substitution was observed to be around 6 wt.% using FTIR and CHNO elemental analyzer. The 6EWCA showed a greater loading (36%) and release (66%) of curcumin than 6SWCA and WHA nanocarriers. The bovine serum albumin (BSA) protein denaturation assay showed the curcumin loaded CAs to be highly anti-inflammatory while their anti-cancer activity was confirmed by the high cytotoxic activity against MG-63 human osteosarcoma cells. Conclusively, an eggshell derived apatite drug delivery system was found to be very suitable to cure osteosarcoma, prevent post-cancer inflammation and modulate bone repair and regeneration.

Antibacterial, anti-inflammatory, and bone-regenerative dual-drug-loaded calcium phosphate nanocarriers-in vitro and in vivo studies.

A dual local drug delivery system (DDS) composed of calcium phosphate bioceramic nanocarriers aimed at treating the antibacterial, anti-inflammatory, and bone-regenerative aspects of periodontitis has been developed. Calcium-deficient hydroxyapatite (CDHA, Ca/P = 1.61) and tricalcium phosphate (ß-TCP) were prepared by microwave-accelerated wet chemical synthesis method. The phase purity of the nanocarriers was confirmed by x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR), while the transmission electron microscopy (TEM) confirmed their nanosized morphology. CDHA was selected as carrier for the antibiotic (tetracycline) while TCP was chosen as the anti-inflammatory drug (ibuprofen) carrier. Combined drug release profile was studied in vitro from CDHA/TCP (CTP) system and compared with a HA/TCP (BCP) biphasic system. The tetracycline and ibuprofen release rate was 71 and 23% from CTP system as compared to 63 and 20% from BCP system. CTP system also showed a more controlled drug release profile compared to BCP system. Modeling of drug release kinetics from CTP system indicated that the release follows Higuchi model with a non-typical Fickian diffusion profile. In vitro biological studies showed the CTP system to be biocompatible with significant antibacterial and anti-inflammatory activity. In vivo implantation studies on rat cranial defects showed greater bone healing and new bone formation in the drug-loaded CTP system compared to control (no carrier) at the end of 12 weeks. The in vitro and in vivo results suggest that the combined drug delivery platform can provide a comprehensive management for all bone infections requiring multi-drug therapy.

Dual mode antibacterial activity of ion substituted calcium phosphate nanocarriers for bone infections.

Nanotechnology has tremendous potential for the management of infectious diseases caused by multi-drug resistant bacteria, through the development of newer antibacterial materials and efficient modes of antibiotic delivery. Calcium phosphate (CaP) bioceramics are commonly used as bone substitutes due to their similarity to bone mineral and are widely researched upon for the treatment of bone infections associated with bone loss. CaPs can be used as local antibiotic delivery agents for bone infections and can be substituted with antibacterial ions in their crystal structure to have a wide spectrum, sustained antibacterial activity even against drug resistant bacteria. In the present work, a dual mode antibiotic delivery system with antibacterial ion substituted calcium deficient hydroxyapatite (CDHA) nanoparticles has been developed. Antibacterial ions such as zinc, silver, and strontium have been incorporated into CDHA at concentrations of 6, 0.25-0.75, and 2.5-7.5 at. %, respectively. The samples were found to be phase pure, acicular nanoparticles of length 40-50 nm and width 5-6 nm approximately. The loading and release profile of doxycycline, a commonly used antibiotic, was studied from the nanocarriers. The drug release was studied for 5 days and the release profile was influenced by the ion concentrations. The release of antibacterial ions was studied over a period of 21 days. The ion substituted CDHA samples were tested for antibacterial efficacy on Staphylococcus aureus and Escherichia coli by MIC/MBC studies and time-kill assay. AgCDHA and ZnCDHA showed high antibacterial activity against both bacteria, while SrCDHA was weakly active against S. aureus. Present study shows that the antibiotic release can provide the initial high antibacterial activity, and the sustained ion release can provide a long-term antibacterial activity. Such dual mode antibiotic and antibacterial ion release offers an efficient and potent way to treat an incumbent drug resistant infection.