Synthetic hydroxyapatite: a recruiting platform for biologically active molecules. Raina, D. B., Liu, Y., Isaksson, H., Tägil, M., & Lidgren, L. Acta orthopaedica, 91(2):126–132, April, 2020. doi abstract bibtex Background and purpose - Targeted delivery of drugs is important to achieve efficient local concentrations and reduce systemic side effects. We hypothesized that locally implanted synthetic hydroxyapatite (HA) particles can act as a recruiting moiety for systemically administered drugs, leading to targeted drug accretion.Methods - Synthetic HA particles were implanted ectopically in a muscle pouch in rats, and the binding of systemically circulating drugs such as zoledronic acid (ZA), tetracycline and (18)F-fluoride ((18)F) was studied. The local biological effect was verified in an implant integration model in rats, wherein a hollow implant was filled with synthetic HA particles and the animals were given systemic ZA, 2-weeks post-implantation. The effect of HA particle size on drug binding and the possibility of reloading HA particles were also evaluated in the muscle pouch.Results - The systemically administered biomolecules (ZA, tetracycline and (18)F) all sought the HA moiety placed in the muscle pouch. Statistically significant higher peri-implant bone volume and peak force were observed in the implant containing HA particles compared with the empty implant. After a single injection of ZA at 2 weeks, micro HA particles showed a tendency to accumulate more (14)C-zoledronic acid ((14)C-ZA) than nano-HA particles in the muscle pouch. HA particles could be reloaded when ZA was given again at 4 weeks, showing increased (14)C-ZA accretion by 73% in microparticles and 77% in nanoparticles.Interpretation - We describe a novel method of systemic drug loading resulting in targeted accretion in locally implanted particulate HA, thereby biologically activating the material.
@article{raina_synthetic_2020,
title = {Synthetic hydroxyapatite: a recruiting platform for biologically active molecules.},
volume = {91},
issn = {1745-3682 1745-3674 1745-3674},
doi = {10.1080/17453674.2019.1686865},
abstract = {Background and purpose - Targeted delivery of drugs is important to achieve efficient local concentrations and reduce systemic side effects. We hypothesized that locally implanted synthetic hydroxyapatite (HA) particles can act as a recruiting moiety for systemically administered drugs, leading to targeted drug accretion.Methods - Synthetic HA particles were implanted ectopically in a muscle pouch in rats, and the binding of systemically circulating drugs such as zoledronic acid (ZA), tetracycline and (18)F-fluoride ((18)F) was studied. The local biological effect was verified in an implant integration model in rats, wherein a hollow implant was filled with synthetic HA particles and the animals were given systemic ZA, 2-weeks post-implantation. The effect of HA particle size on drug binding and the possibility of reloading HA particles were also evaluated in the muscle pouch.Results - The systemically administered biomolecules (ZA, tetracycline and (18)F) all sought the HA moiety placed in the muscle pouch. Statistically significant higher peri-implant bone volume and peak force were observed in the implant containing HA particles compared with the empty implant. After a single injection of ZA at 2 weeks, micro HA particles showed a tendency to accumulate more (14)C-zoledronic acid ((14)C-ZA) than nano-HA particles in the muscle pouch. HA particles could be reloaded when ZA was given again at 4 weeks, showing increased (14)C-ZA accretion by 73\% in microparticles and 77\% in nanoparticles.Interpretation - We describe a novel method of systemic drug loading resulting in targeted accretion in locally implanted particulate HA, thereby biologically activating the material.},
language = {eng},
number = {2},
journal = {Acta orthopaedica},
author = {Raina, Deepak Bushan and Liu, Yang and Isaksson, Hanna and Tägil, Magnus and Lidgren, Lars},
month = apr,
year = {2020},
pmid = {31680611},
pmcid = {PMC7144254},
keywords = {*Drug Delivery Systems, Animals, Anti-Bacterial Agents/administration \& dosage/pharmacokinetics, Bone Density Conservation Agents/*administration \& dosage/pharmacokinetics, Coated Materials, Biocompatible, Drug Carriers, Durapatite/*metabolism, Fluorides/administration \& dosage/pharmacokinetics, Implants, Experimental, Male, Particle Size, Positron Emission Tomography Computed Tomography, Rats, Sprague-Dawley, Tetracycline/administration \& dosage/pharmacokinetics, Zoledronic Acid/*administration \& dosage/pharmacokinetics},
pages = {126--132},
}
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We hypothesized that locally implanted synthetic hydroxyapatite (HA) particles can act as a recruiting moiety for systemically administered drugs, leading to targeted drug accretion.Methods - Synthetic HA particles were implanted ectopically in a muscle pouch in rats, and the binding of systemically circulating drugs such as zoledronic acid (ZA), tetracycline and (18)F-fluoride ((18)F) was studied. The local biological effect was verified in an implant integration model in rats, wherein a hollow implant was filled with synthetic HA particles and the animals were given systemic ZA, 2-weeks post-implantation. The effect of HA particle size on drug binding and the possibility of reloading HA particles were also evaluated in the muscle pouch.Results - The systemically administered biomolecules (ZA, tetracycline and (18)F) all sought the HA moiety placed in the muscle pouch. Statistically significant higher peri-implant bone volume and peak force were observed in the implant containing HA particles compared with the empty implant. After a single injection of ZA at 2 weeks, micro HA particles showed a tendency to accumulate more (14)C-zoledronic acid ((14)C-ZA) than nano-HA particles in the muscle pouch. HA particles could be reloaded when ZA was given again at 4 weeks, showing increased (14)C-ZA accretion by 73% in microparticles and 77% in nanoparticles.Interpretation - We describe a novel method of systemic drug loading resulting in targeted accretion in locally implanted particulate HA, thereby biologically activating the material.","language":"eng","number":"2","journal":"Acta orthopaedica","author":[{"propositions":[],"lastnames":["Raina"],"firstnames":["Deepak","Bushan"],"suffixes":[]},{"propositions":[],"lastnames":["Liu"],"firstnames":["Yang"],"suffixes":[]},{"propositions":[],"lastnames":["Isaksson"],"firstnames":["Hanna"],"suffixes":[]},{"propositions":[],"lastnames":["Tägil"],"firstnames":["Magnus"],"suffixes":[]},{"propositions":[],"lastnames":["Lidgren"],"firstnames":["Lars"],"suffixes":[]}],"month":"April","year":"2020","pmid":"31680611","pmcid":"PMC7144254","keywords":"*Drug Delivery Systems, Animals, Anti-Bacterial Agents/administration & dosage/pharmacokinetics, Bone Density Conservation Agents/*administration & dosage/pharmacokinetics, Coated Materials, Biocompatible, Drug Carriers, Durapatite/*metabolism, Fluorides/administration & dosage/pharmacokinetics, Implants, Experimental, Male, Particle Size, Positron Emission Tomography Computed Tomography, Rats, Sprague-Dawley, Tetracycline/administration & dosage/pharmacokinetics, Zoledronic Acid/*administration & dosage/pharmacokinetics","pages":"126–132","bibtex":"@article{raina_synthetic_2020,\n\ttitle = {Synthetic hydroxyapatite: a recruiting platform for biologically active molecules.},\n\tvolume = {91},\n\tissn = {1745-3682 1745-3674 1745-3674},\n\tdoi = {10.1080/17453674.2019.1686865},\n\tabstract = {Background and purpose - Targeted delivery of drugs is important to achieve efficient local concentrations and reduce systemic side effects. We hypothesized that locally implanted synthetic hydroxyapatite (HA) particles can act as a recruiting moiety for systemically administered drugs, leading to targeted drug accretion.Methods - Synthetic HA particles were implanted ectopically in a muscle pouch in rats, and the binding of systemically circulating drugs such as zoledronic acid (ZA), tetracycline and (18)F-fluoride ((18)F) was studied. The local biological effect was verified in an implant integration model in rats, wherein a hollow implant was filled with synthetic HA particles and the animals were given systemic ZA, 2-weeks post-implantation. The effect of HA particle size on drug binding and the possibility of reloading HA particles were also evaluated in the muscle pouch.Results - The systemically administered biomolecules (ZA, tetracycline and (18)F) all sought the HA moiety placed in the muscle pouch. Statistically significant higher peri-implant bone volume and peak force were observed in the implant containing HA particles compared with the empty implant. After a single injection of ZA at 2 weeks, micro HA particles showed a tendency to accumulate more (14)C-zoledronic acid ((14)C-ZA) than nano-HA particles in the muscle pouch. 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