Mechanism of enhanced antiosteoporosis effect of circinal–icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate

Mechanism of enhanced antiosteoporosis effect of circinal–icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate

Jun Jiang,1,2 Jie Li,1,2 Zhenhai Zhang,1,2 E Sun,1,2 Liang Feng,1,2 Xiaobin Jia1,21Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, 2College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People’s Republic...

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Autores principales: Jiang J, Li J, Zhang ZH, Sun E, Feng L, Jia XB
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
Materias:
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/5dd9596ea78b4c5ba0748d2f74f5c1dd
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spelling oai:doaj.org-article:5dd9596ea78b4c5ba0748d2f74f5c1dd2021-12-02T01:13:34ZMechanism of enhanced antiosteoporosis effect of circinal–icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate1178-2013https://doaj.org/article/5dd9596ea78b4c5ba0748d2f74f5c1dd2015-03-01T00:00:00Zhttp://www.dovepress.com/mechanism-of-enhanced-antiosteoporosis-effect-ofnbspcircinalndashicari-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Jun Jiang,1,2 Jie Li,1,2 Zhenhai Zhang,1,2 E Sun,1,2 Liang Feng,1,2 Xiaobin Jia1,21Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, 2College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaBackground: Circinal–icaritin (CIT), one new active aglycone of Epimedium, can exert a beneficial effect on osteoporotic bone. However, its low bioavailability limits its clinical efficacy for the treatment of osteoporosis.Materials and methods: In this paper, suet oil (SO) was used to improve the oral bioavailability of CIT and enhance its antiosteoporosis effect and absorption. After oral administration of CIT together with SO, the CIT and SO self-assembled into nanomicelles under the action of sodium deoxycholate (DOC) by bile secretion. The antiosteoporosis effects of the CIT-SO-DOC nanomicelles were evaluated in osteoporotic rats by bone mineral density, serum biochemical markers, bone microarchitecture, bone biomechanical properties, and related protein and gene expressions. We examined the bioavailability of CIT and its nanomicelles in vivo, and subsequently the nanomicelles were verified using transmission electron microscopy. Finally, we evaluated absorption across a rat intestinal perfusion model.Results: Compared with CIT, in the CIT-SO groups, protein and messenger ribonucleic acid expressions of osteoprotegerin were increased, while expressions of receptor activator of nuclear factor-κB ligand in bone tissue were decreased; bone-turnover markers in serum of hydroxyproline, alkaline phosphatase, tartrate-resistant acid phosphatase 5b, and receptor activator of nuclear factor-κB ligand levels were decreased, while osteoprotegerin and osteocalcin levels were increased; and trabecular bone mass, microarchitecture, and bone biomechanical strength were enhanced. The relative bioavailabilities of CIT-SO high dosage, CIT-SO medium dosage, and CIT-SO low dosage (area under concentration–time curve [AUC]0–∞) compared with that of raw CIT high dosage, CIT medium dosage, and CIT low dosage (AUC0–∞) were 127%, 121%, and 134%, respectively. The average particle size of CIT-DOC was significantly decreased after adding SO (P<0.01), and the intestinal permeability coefficients of CIT-SO-DOC nanomicelles in the duodenum, jejunum, ileum, and colon were all significantly improved (P<0.01).Conclusion: The increased antiosteoporosis effects and bioavailability of CIT-SO-DOC self-assembled nanomicelles were due to an increase in absorption of CIT by reducing the particle sizes of CIT. SO may be a practical oral carrier for antiosteoporosis drugs with low bioavailability.Keywords: circinal–icaritin (CIT), nanomicelles, antiosteoporosis effect, bioavailability, intestinal absorptionJiang JLi JZhang ZHSun EFeng LJia XBDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 2377-2389 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Jiang J
Li J
Zhang ZH
Sun E
Feng L
Jia XB
Mechanism of enhanced antiosteoporosis effect of circinal–icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate
description Jun Jiang,1,2 Jie Li,1,2 Zhenhai Zhang,1,2 E Sun,1,2 Liang Feng,1,2 Xiaobin Jia1,21Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, 2College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaBackground: Circinal–icaritin (CIT), one new active aglycone of Epimedium, can exert a beneficial effect on osteoporotic bone. However, its low bioavailability limits its clinical efficacy for the treatment of osteoporosis.Materials and methods: In this paper, suet oil (SO) was used to improve the oral bioavailability of CIT and enhance its antiosteoporosis effect and absorption. After oral administration of CIT together with SO, the CIT and SO self-assembled into nanomicelles under the action of sodium deoxycholate (DOC) by bile secretion. The antiosteoporosis effects of the CIT-SO-DOC nanomicelles were evaluated in osteoporotic rats by bone mineral density, serum biochemical markers, bone microarchitecture, bone biomechanical properties, and related protein and gene expressions. We examined the bioavailability of CIT and its nanomicelles in vivo, and subsequently the nanomicelles were verified using transmission electron microscopy. Finally, we evaluated absorption across a rat intestinal perfusion model.Results: Compared with CIT, in the CIT-SO groups, protein and messenger ribonucleic acid expressions of osteoprotegerin were increased, while expressions of receptor activator of nuclear factor-κB ligand in bone tissue were decreased; bone-turnover markers in serum of hydroxyproline, alkaline phosphatase, tartrate-resistant acid phosphatase 5b, and receptor activator of nuclear factor-κB ligand levels were decreased, while osteoprotegerin and osteocalcin levels were increased; and trabecular bone mass, microarchitecture, and bone biomechanical strength were enhanced. The relative bioavailabilities of CIT-SO high dosage, CIT-SO medium dosage, and CIT-SO low dosage (area under concentration–time curve [AUC]0–∞) compared with that of raw CIT high dosage, CIT medium dosage, and CIT low dosage (AUC0–∞) were 127%, 121%, and 134%, respectively. The average particle size of CIT-DOC was significantly decreased after adding SO (P<0.01), and the intestinal permeability coefficients of CIT-SO-DOC nanomicelles in the duodenum, jejunum, ileum, and colon were all significantly improved (P<0.01).Conclusion: The increased antiosteoporosis effects and bioavailability of CIT-SO-DOC self-assembled nanomicelles were due to an increase in absorption of CIT by reducing the particle sizes of CIT. SO may be a practical oral carrier for antiosteoporosis drugs with low bioavailability.Keywords: circinal–icaritin (CIT), nanomicelles, antiosteoporosis effect, bioavailability, intestinal absorption
format article
author Jiang J
Li J
Zhang ZH
Sun E
Feng L
Jia XB
author_facet Jiang J
Li J
Zhang ZH
Sun E
Feng L
Jia XB
author_sort Jiang J
title Mechanism of enhanced antiosteoporosis effect of circinal–icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate
title_short Mechanism of enhanced antiosteoporosis effect of circinal–icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate
title_full Mechanism of enhanced antiosteoporosis effect of circinal–icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate
title_fullStr Mechanism of enhanced antiosteoporosis effect of circinal–icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate
title_full_unstemmed Mechanism of enhanced antiosteoporosis effect of circinal–icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate
title_sort mechanism of enhanced antiosteoporosis effect of circinal–icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/5dd9596ea78b4c5ba0748d2f74f5c1dd
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