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Synthetic hydroxyapatite : a recruiting platform for biologically active molecules

Raina, Deepak Bushan LU ; Liu, Yang LU ; Isaksson, Hanna LU ; Tägil, Magnus LU and Lidgren, Lars LU (2019) In Acta Orthopaedica
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
organization
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type
Contribution to journal
publication status
epub
subject
in
Acta Orthopaedica
publisher
Taylor & Francis
external identifiers
  • pmid:31680611
  • scopus:85075011600
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
2019-12-04 07:24:41
@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},
  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},
  year         = {2019},
}