Assessing the safety of transarterial locoregional delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat liver
Junjie Li, Diana Canseco, Yuzhu Wang, Gonçalo Vale, Jaideep Chaudhary, Arnida Anwar, Hamid Baniasadi, Noelle S. Williams, Purva Gopal, Patrick D. Sutphin, Jeffrey G. McDonald, William C. Putnam, Ian R. Corbin
Center For Human Nutrition
The Center for Human Nutrition
BY - Core Metabolomics
Hepatic-arterial infusion (HAI) of low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) (LDL-DHA) has been shown in a rat hepatoma model to be a promising treatment for hepatocellular carcinoma. To date, little is known regarding the safety of HAI of LDL-DHA to the liver. Therefore, we aimed to investigate the deposition, metabolism and safety of HAI of LDL-DHA (2, 4 or 8 mg/kg) in the rat. Following HAI, fluorescent labeled LDL nanoparticles displayed a biexponential plasma concentration time curve as the particles were rapidly extracted by the liver. Overall, increasing doses of HAI of LDL-DHA was well tolerated in the rat. Body weight, plasma biochemistry and histology were all unremarkable and molecular markers of inflammation did not increase with treatment. Lipidomics analyses showed that LDL-DHA was preferentially oxidized to the anti-inflammatory mediator, protectin DX. We conclude that HAI of LDL-DHA nanoparticles is not only safe, but provides potential hepatoprotective benefits.
European Journal of Pharmaceutics and Biopharmaceutics
https://doi.org/10.1016/j.ejpb.2020.10.018
Docosahexaenoic acid
Locoregional delivery
Low-density lipoprotein
Nanoparticle safety
10.1016/j.ejpb.2020.10.018
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Docosahexaenoic Acid Chemical Compounds 100%
Docosahexaenoic Acids Medicine & Life Sciences 88%
LDL Lipoproteins Medicine & Life Sciences 77%
Nanoparticles Medicine & Life Sciences 66%
Nanoparticle Chemical Compounds 37%
Acid Chemical Compounds 25%
Li, J., Canseco, D., Wang, Y., Vale, G., Chaudhary, J., Anwar, A., Baniasadi, H., Williams, N. S., Gopal, P., Sutphin, P. D., McDonald, J. G., Putnam, W. C., & Corbin, I. R. (2021). Assessing the safety of transarterial locoregional delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat liver. European Journal of Pharmaceutics and Biopharmaceutics, 158, 273-283. https://doi.org/10.1016/j.ejpb.2020.10.018
Assessing the safety of transarterial locoregional delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat liver. / Li, Junjie; Canseco, Diana; Wang, Yuzhu; Vale, Gonçalo; Chaudhary, Jaideep; Anwar, Arnida; Baniasadi, Hamid; Williams, Noelle S.; Gopal, Purva; Sutphin, Patrick D.; McDonald, Jeffrey G.; Putnam, William C.; Corbin, Ian R.
In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 158, 01.2021, p. 273-283.
Li, J, Canseco, D, Wang, Y, Vale, G, Chaudhary, J, Anwar, A, Baniasadi, H, Williams, NS, Gopal, P, Sutphin, PD, McDonald, JG, Putnam, WC & Corbin, IR 2021, 'Assessing the safety of transarterial locoregional delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat liver', European Journal of Pharmaceutics and Biopharmaceutics, vol. 158, pp. 273-283. https://doi.org/10.1016/j.ejpb.2020.10.018
Li J, Canseco D, Wang Y, Vale G, Chaudhary J, Anwar A et al. Assessing the safety of transarterial locoregional delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat liver. European Journal of Pharmaceutics and Biopharmaceutics. 2021 Jan;158:273-283. https://doi.org/10.1016/j.ejpb.2020.10.018
Li, Junjie ; Canseco, Diana ; Wang, Yuzhu ; Vale, Gonçalo ; Chaudhary, Jaideep ; Anwar, Arnida ; Baniasadi, Hamid ; Williams, Noelle S. ; Gopal, Purva ; Sutphin, Patrick D. ; McDonald, Jeffrey G. ; Putnam, William C. ; Corbin, Ian R. / Assessing the safety of transarterial locoregional delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat liver. In: European Journal of Pharmaceutics and Biopharmaceutics. 2021 ; Vol. 158. pp. 273-283.
@article{82997d0d46aa48e0bb21cb36e20500d5,
title = "Assessing the safety of transarterial locoregional delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat liver",
abstract = "Hepatic-arterial infusion (HAI) of low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) (LDL-DHA) has been shown in a rat hepatoma model to be a promising treatment for hepatocellular carcinoma. To date, little is known regarding the safety of HAI of LDL-DHA to the liver. Therefore, we aimed to investigate the deposition, metabolism and safety of HAI of LDL-DHA (2, 4 or 8 mg/kg) in the rat. Following HAI, fluorescent labeled LDL nanoparticles displayed a biexponential plasma concentration time curve as the particles were rapidly extracted by the liver. Overall, increasing doses of HAI of LDL-DHA was well tolerated in the rat. Body weight, plasma biochemistry and histology were all unremarkable and molecular markers of inflammation did not increase with treatment. Lipidomics analyses showed that LDL-DHA was preferentially oxidized to the anti-inflammatory mediator, protectin DX. We conclude that HAI of LDL-DHA nanoparticles is not only safe, but provides potential hepatoprotective benefits.",
keywords = "Docosahexaenoic acid, Locoregional delivery, Low-density lipoprotein, Nanomedicine, Nanoparticle safety, Toxicity",
author = "Junjie Li and Diana Canseco and Yuzhu Wang and Gon{\c c}alo Vale and Jaideep Chaudhary and Arnida Anwar and Hamid Baniasadi and Williams, {Noelle S.} and Purva Gopal and Sutphin, {Patrick D.} and McDonald, {Jeffrey G.} and Putnam, {William C.} and Corbin, {Ian R.}",
note = "Funding Information: This work was supported in part by Remeditex ventures LCC OTD-109946, NCI, National Institutes of Health (NIH), Grant R01CA215702, Society of Interventional Radiology Foundation Dr. Ernest J. Ring Academic Development Grant, the Henan University visiting scholar program (2016051) and the UTSW Cancer Center Support Grant (5P30 CA 142543-05) and the Cancer Prevention Research Institute of Texas Core Facilities Support Award (RP170003; to W.C.P.). Funding Information: We are grateful to Dr. John Shelton and Ms. Bonne Thompson for providing technical experimental assistance with histopathology and lipidomics respectively. We would like to acknowledge the support from Remeditex ventures LCC OTD-109946, NCI, National Institutes of Health (NIH), Grant R01CA215702, Society of Interventional Radiology Foundation Dr. Ernest J. Ring Academic Development Grant, the Henan University visiting scholar program (2016051) and the UTSW Cancer Center Support Grant (5P30 CA 142543-05) and the Cancer Prevention Research Institute of Texas Core Facilities Support Award (RP170003; to W.C.P.). Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",
doi = "10.1016/j.ejpb.2020.10.018",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
T1 - Assessing the safety of transarterial locoregional delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat liver
AU - Li, Junjie
AU - Canseco, Diana
AU - Wang, Yuzhu
AU - Vale, Gonçalo
AU - Chaudhary, Jaideep
AU - Anwar, Arnida
AU - Baniasadi, Hamid
AU - Williams, Noelle S.
AU - Gopal, Purva
AU - Sutphin, Patrick D.
AU - McDonald, Jeffrey G.
AU - Putnam, William C.
AU - Corbin, Ian R.
N1 - Funding Information: This work was supported in part by Remeditex ventures LCC OTD-109946, NCI, National Institutes of Health (NIH), Grant R01CA215702, Society of Interventional Radiology Foundation Dr. Ernest J. Ring Academic Development Grant, the Henan University visiting scholar program (2016051) and the UTSW Cancer Center Support Grant (5P30 CA 142543-05) and the Cancer Prevention Research Institute of Texas Core Facilities Support Award (RP170003; to W.C.P.). Funding Information: We are grateful to Dr. John Shelton and Ms. Bonne Thompson for providing technical experimental assistance with histopathology and lipidomics respectively. We would like to acknowledge the support from Remeditex ventures LCC OTD-109946, NCI, National Institutes of Health (NIH), Grant R01CA215702, Society of Interventional Radiology Foundation Dr. Ernest J. Ring Academic Development Grant, the Henan University visiting scholar program (2016051) and the UTSW Cancer Center Support Grant (5P30 CA 142543-05) and the Cancer Prevention Research Institute of Texas Core Facilities Support Award (RP170003; to W.C.P.). Publisher Copyright: © 2020 Elsevier B.V.
N2 - Hepatic-arterial infusion (HAI) of low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) (LDL-DHA) has been shown in a rat hepatoma model to be a promising treatment for hepatocellular carcinoma. To date, little is known regarding the safety of HAI of LDL-DHA to the liver. Therefore, we aimed to investigate the deposition, metabolism and safety of HAI of LDL-DHA (2, 4 or 8 mg/kg) in the rat. Following HAI, fluorescent labeled LDL nanoparticles displayed a biexponential plasma concentration time curve as the particles were rapidly extracted by the liver. Overall, increasing doses of HAI of LDL-DHA was well tolerated in the rat. Body weight, plasma biochemistry and histology were all unremarkable and molecular markers of inflammation did not increase with treatment. Lipidomics analyses showed that LDL-DHA was preferentially oxidized to the anti-inflammatory mediator, protectin DX. We conclude that HAI of LDL-DHA nanoparticles is not only safe, but provides potential hepatoprotective benefits.
AB - Hepatic-arterial infusion (HAI) of low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) (LDL-DHA) has been shown in a rat hepatoma model to be a promising treatment for hepatocellular carcinoma. To date, little is known regarding the safety of HAI of LDL-DHA to the liver. Therefore, we aimed to investigate the deposition, metabolism and safety of HAI of LDL-DHA (2, 4 or 8 mg/kg) in the rat. Following HAI, fluorescent labeled LDL nanoparticles displayed a biexponential plasma concentration time curve as the particles were rapidly extracted by the liver. Overall, increasing doses of HAI of LDL-DHA was well tolerated in the rat. Body weight, plasma biochemistry and histology were all unremarkable and molecular markers of inflammation did not increase with treatment. Lipidomics analyses showed that LDL-DHA was preferentially oxidized to the anti-inflammatory mediator, protectin DX. We conclude that HAI of LDL-DHA nanoparticles is not only safe, but provides potential hepatoprotective benefits.
KW - Docosahexaenoic acid
KW - Locoregional delivery
KW - Low-density lipoprotein
KW - Nanomedicine
KW - Nanoparticle safety
KW - Toxicity
U2 - 10.1016/j.ejpb.2020.10.018
DO - 10.1016/j.ejpb.2020.10.018
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics