Synthetic hydroxyapatite: a recruiting platform for biologically active molecules
(2019) In Acta Orthopaedica 19(2).- 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 18F-fluoride (18F) 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... (More)
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 18F-fluoride (18F) 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 18F) 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 14C-zoledronic acid (14C-ZA) than nano-HA particles in the muscle pouch. HA particles could be reloaded when ZA was given again at 4 weeks, showing increased 14C-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.
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- author
- Raina, Deepak Bushan LU ; Liu, Yang LU ; Isaksson, Hanna LU ; Tägil, Magnus LU and Lidgren, Lars LU
- organization
- publishing date
- 2019-11-04
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Acta Orthopaedica
- volume
- 19
- issue
- 2
- publisher
- Taylor & Francis
- external identifiers
-
- scopus:85075011600
- pmid:31680611
- ISSN
- 1745-3674
- DOI
- 10.1080/17453674.2019.1686865
- language
- English
- LU publication?
- yes
- id
- c88ac136-7f40-4706-a6ba-a8aab1bc9325
- date added to LUP
- 2019-12-03 12:27:54
- date last changed
- 2024-09-18 14:05:47
@article{c88ac136-7f40-4706-a6ba-a8aab1bc9325, abstract = {{<p>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 <sup>18</sup>F-fluoride (<sup>18</sup>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 <sup>18</sup>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 <sup>14</sup>C-zoledronic acid (<sup>14</sup>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 <sup>14</sup>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.</p>}}, author = {{Raina, Deepak Bushan and Liu, Yang and Isaksson, Hanna and Tägil, Magnus and Lidgren, Lars}}, issn = {{1745-3674}}, language = {{eng}}, month = {{11}}, number = {{2}}, publisher = {{Taylor & Francis}}, series = {{Acta Orthopaedica}}, title = {{Synthetic hydroxyapatite: a recruiting platform for biologically active molecules}}, url = {{http://dx.doi.org/10.1080/17453674.2019.1686865}}, doi = {{10.1080/17453674.2019.1686865}}, volume = {{19}}, year = {{2019}}, }