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Synthetic hydroxyapatite: a recruiting platform for biologically active molecules

Raina, Deepak Bushan LU ; Liu, Yang LU ; Isaksson, Hanna LU orcid ; Tägil, Magnus LU and Lidgren, Lars LU (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
; ; ; and
organization
publishing date
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
2025-10-31 04:25:06
@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}},
}