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Longitudinal in vivo biodistribution of nano and micro sized hydroxyapatite particles implanted in a bone defect

Liu, Yang LU ; Sebastian, Sujeesh LU orcid ; Huang, Jintian LU ; Corbascio, Tova ; Engellau, Jacob LU ; Lidgren, Lars LU ; Tägil, Magnus LU and Raina, Deepak Bushan LU (2022) In Frontiers in Bioengineering and Biotechnology 10.
Abstract

Hydroxyapatite (HA) has been widely used as a bone substitute and more recently as a carrier for local delivery of bone targeted drugs. Majority of the approved HA based biomaterials and drug carriers comprise of micrometer sized particulate HA (mHA) or granules and can therefore only be used for extracellular drug release. This shortcoming could be overcome with the use of cell penetrating HA nanoparticles (nHA) but a major concern with the clinical use of nHA is the lack of data on its in vivo biodistribution after implantation. In this study, we aimed to study the in vivo biodistribution of locally implanted nHA in a clinically relevant tibial void in rats and compare it with mHA or a combination of mHA and nHA. To enable in vivo... (More)

Hydroxyapatite (HA) has been widely used as a bone substitute and more recently as a carrier for local delivery of bone targeted drugs. Majority of the approved HA based biomaterials and drug carriers comprise of micrometer sized particulate HA (mHA) or granules and can therefore only be used for extracellular drug release. This shortcoming could be overcome with the use of cell penetrating HA nanoparticles (nHA) but a major concern with the clinical use of nHA is the lack of data on its in vivo biodistribution after implantation. In this study, we aimed to study the in vivo biodistribution of locally implanted nHA in a clinically relevant tibial void in rats and compare it with mHA or a combination of mHA and nHA. To enable in vivo tracking, HA particles were first labelled with 14C-zoledronic acid (14C-ZA), known to have a high binding affinity to HA. The labelled particles were then implanted in the animals and the radioactivity in the proximal tibia and vital organs was detected at various time points (Day 1, 7 and 28) post-implantation using scintillation counting. The local distribution of the particles in the bone was studied with micro-CT. We found that majority (>99.9%) of the implanted HA particles, irrespective of the size, stayed locally at the implantation site even after 28 days and the findings were confirmed using micro-CT. Less than 0.1% radioactivity was observed in the kidney and the spleen at later time points of day 7 and 28. No pathological changes in any of the vital organs could be observed histologically. This is the first longitudinal in vivo HA biodistribution study showing that the local implantation of nHA particles in bone is safe and that nHA could potentially be used for localized drug delivery.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biodistribution, drug delivery, micro hydroxyapatite, nano hydroxyapatite, osteosarcoma
in
Frontiers in Bioengineering and Biotechnology
volume
10
article number
1076320
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85145349257
  • pmid:36601389
ISSN
2296-4185
DOI
10.3389/fbioe.2022.1076320
language
English
LU publication?
yes
id
7c31fe9c-03f2-421c-b312-190337351d87
date added to LUP
2023-01-16 15:19:47
date last changed
2024-06-13 01:49:17
@article{7c31fe9c-03f2-421c-b312-190337351d87,
  abstract     = {{<p>Hydroxyapatite (HA) has been widely used as a bone substitute and more recently as a carrier for local delivery of bone targeted drugs. Majority of the approved HA based biomaterials and drug carriers comprise of micrometer sized particulate HA (mHA) or granules and can therefore only be used for extracellular drug release. This shortcoming could be overcome with the use of cell penetrating HA nanoparticles (nHA) but a major concern with the clinical use of nHA is the lack of data on its in vivo biodistribution after implantation. In this study, we aimed to study the in vivo biodistribution of locally implanted nHA in a clinically relevant tibial void in rats and compare it with mHA or a combination of mHA and nHA. To enable in vivo tracking, HA particles were first labelled with <sup>14</sup>C-zoledronic acid (<sup>14</sup>C-ZA), known to have a high binding affinity to HA. The labelled particles were then implanted in the animals and the radioactivity in the proximal tibia and vital organs was detected at various time points (Day 1, 7 and 28) post-implantation using scintillation counting. The local distribution of the particles in the bone was studied with micro-CT. We found that majority (&gt;99.9%) of the implanted HA particles, irrespective of the size, stayed locally at the implantation site even after 28 days and the findings were confirmed using micro-CT. Less than 0.1% radioactivity was observed in the kidney and the spleen at later time points of day 7 and 28. No pathological changes in any of the vital organs could be observed histologically. This is the first longitudinal in vivo HA biodistribution study showing that the local implantation of nHA particles in bone is safe and that nHA could potentially be used for localized drug delivery.</p>}},
  author       = {{Liu, Yang and Sebastian, Sujeesh and Huang, Jintian and Corbascio, Tova and Engellau, Jacob and Lidgren, Lars and Tägil, Magnus and Raina, Deepak Bushan}},
  issn         = {{2296-4185}},
  keywords     = {{biodistribution; drug delivery; micro hydroxyapatite; nano hydroxyapatite; osteosarcoma}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Bioengineering and Biotechnology}},
  title        = {{Longitudinal in vivo biodistribution of nano and micro sized hydroxyapatite particles implanted in a bone defect}},
  url          = {{http://dx.doi.org/10.3389/fbioe.2022.1076320}},
  doi          = {{10.3389/fbioe.2022.1076320}},
  volume       = {{10}},
  year         = {{2022}},
}