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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