Co-Delivery of Prednisolone and Curcumin in Human Serum Albumin Nanoparticles for Effective Treatment of Rheumatoid Arthritis

Feili Yan,1,* Hui Li,1,* Zhirong Zhong,1,* Meiling Zhou,2 Yan Lin,1 Can Tang,1 Chunhong Li1 1Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, People’s Republic of China; 2Department of Pharmacy, The Affiliated Hospital of Sout...

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Autores principales:	Yan F, Li H, Zhong Z, Zhou M, Lin Y, Tang C, Li C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	co-delivery prednisolone curcumin human serum albumin rheumatoid arthritis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8e1d1cf13b044565b6ec65c1f396abff
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spelling	oai:doaj.org-article:8e1d1cf13b044565b6ec65c1f396abff2021-12-02T05:21:50ZCo-Delivery of Prednisolone and Curcumin in Human Serum Albumin Nanoparticles for Effective Treatment of Rheumatoid Arthritis1178-2013https://doaj.org/article/8e1d1cf13b044565b6ec65c1f396abff2019-11-01T00:00:00Zhttps://www.dovepress.com/co-delivery-of-prednisolone-and-curcumin-in-human-serum-albumin-nanopa-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Feili Yan,1,* Hui Li,1,* Zhirong Zhong,1,* Meiling Zhou,2 Yan Lin,1 Can Tang,1 Chunhong Li1 1Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, People’s Republic of China; 2Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Can Tang; Chunhong LiDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, 3-319 Zhongshan Road, Luzhou, Sichuan 646000, People’s Republic of ChinaTel +86 18982455783; +86 13679696586Fax +86 08306302050Email 2291691527@qq.com; lispringhong@126.comBackground: Prednisolone (PD) is extremely effective for treating rheumatoid arthritis (RA). However, it distributes nonspecifically throughout the body and its use is associated with serious side effects, which promoted us to compound it into a phytomedicine for greater efficacy and safety.Methods: We combined PD with curcumin (CU), an effective monomer from traditional Chinese medicine, and human serum albumin (HSA) in a nanoparticulate system (N-PD/CU) to compensate for the poor bioavailability of PD and CU. N-PD/CU was prepared by high-pressure homogenization, and its characteristics were evaluated in vitro. Next, we investigated its toxicity and mechanism of anti-inflammatory to macrophages. Finally, its pharmacokinetics, biodistribution and therapeutic efficacy were assessed in rats with adjuvant-induced arthritis (AIA).Results: N-PD/CU showed a narrow size distribution around 150.4 ± 2.4 nm, a polydispersity index of 0.22 ± 0.02 and drug loading efficiency (DLE) of 88.75 ± 1.82% for PD and 85.79 ± 1.43% for CU. N-PD/CU showed sustained release of both drugs in vitro. N-PD/CU had no toxicity to macrophages in vitro on concentrations between 0.1 and 1.2 μmol/mL. In activated macrophages, N-PD decreased levels of pro-inflammatory cytokines, while N-CU increased levels of anti-inflammatory IL-10, and N-PD/CU exhibited best therapeutic effect in vitro, suggesting co-delivery of PD and CU may synergistically control the course of RA. In AIA rats, N-PD/CU accumulated in inflamed joints through the effect of extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS effect) in inflammatory lesion and showed higher therapeutic efficacy than single-loaded nanoparticles, either free drug on its own, or a simple mixture of the two drugs.Conclusion: This codelivery system based on HSA is a promising platform for combination chemotherapy in RA.Keywords: co-delivery, prednisolone, curcumin, human serum albumin, rheumatoid arthritisYan FLi HZhong ZZhou MLin YTang CLi CDove Medical Pressarticleco-deliveryprednisolonecurcuminhuman serum albuminrheumatoid arthritisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 9113-9125 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	co-delivery prednisolone curcumin human serum albumin rheumatoid arthritis Medicine (General) R5-920
spellingShingle	co-delivery prednisolone curcumin human serum albumin rheumatoid arthritis Medicine (General) R5-920 Yan F Li H Zhong Z Zhou M Lin Y Tang C Li C Co-Delivery of Prednisolone and Curcumin in Human Serum Albumin Nanoparticles for Effective Treatment of Rheumatoid Arthritis
description	Feili Yan,1,* Hui Li,1,* Zhirong Zhong,1,* Meiling Zhou,2 Yan Lin,1 Can Tang,1 Chunhong Li1 1Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, People’s Republic of China; 2Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Can Tang; Chunhong LiDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, 3-319 Zhongshan Road, Luzhou, Sichuan 646000, People’s Republic of ChinaTel +86 18982455783; +86 13679696586Fax +86 08306302050Email 2291691527@qq.com; lispringhong@126.comBackground: Prednisolone (PD) is extremely effective for treating rheumatoid arthritis (RA). However, it distributes nonspecifically throughout the body and its use is associated with serious side effects, which promoted us to compound it into a phytomedicine for greater efficacy and safety.Methods: We combined PD with curcumin (CU), an effective monomer from traditional Chinese medicine, and human serum albumin (HSA) in a nanoparticulate system (N-PD/CU) to compensate for the poor bioavailability of PD and CU. N-PD/CU was prepared by high-pressure homogenization, and its characteristics were evaluated in vitro. Next, we investigated its toxicity and mechanism of anti-inflammatory to macrophages. Finally, its pharmacokinetics, biodistribution and therapeutic efficacy were assessed in rats with adjuvant-induced arthritis (AIA).Results: N-PD/CU showed a narrow size distribution around 150.4 ± 2.4 nm, a polydispersity index of 0.22 ± 0.02 and drug loading efficiency (DLE) of 88.75 ± 1.82% for PD and 85.79 ± 1.43% for CU. N-PD/CU showed sustained release of both drugs in vitro. N-PD/CU had no toxicity to macrophages in vitro on concentrations between 0.1 and 1.2 μmol/mL. In activated macrophages, N-PD decreased levels of pro-inflammatory cytokines, while N-CU increased levels of anti-inflammatory IL-10, and N-PD/CU exhibited best therapeutic effect in vitro, suggesting co-delivery of PD and CU may synergistically control the course of RA. In AIA rats, N-PD/CU accumulated in inflamed joints through the effect of extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS effect) in inflammatory lesion and showed higher therapeutic efficacy than single-loaded nanoparticles, either free drug on its own, or a simple mixture of the two drugs.Conclusion: This codelivery system based on HSA is a promising platform for combination chemotherapy in RA.Keywords: co-delivery, prednisolone, curcumin, human serum albumin, rheumatoid arthritis
format	article
author	Yan F Li H Zhong Z Zhou M Lin Y Tang C Li C
author_facet	Yan F Li H Zhong Z Zhou M Lin Y Tang C Li C
author_sort	Yan F
title	Co-Delivery of Prednisolone and Curcumin in Human Serum Albumin Nanoparticles for Effective Treatment of Rheumatoid Arthritis
title_short	Co-Delivery of Prednisolone and Curcumin in Human Serum Albumin Nanoparticles for Effective Treatment of Rheumatoid Arthritis
title_full	Co-Delivery of Prednisolone and Curcumin in Human Serum Albumin Nanoparticles for Effective Treatment of Rheumatoid Arthritis
title_fullStr	Co-Delivery of Prednisolone and Curcumin in Human Serum Albumin Nanoparticles for Effective Treatment of Rheumatoid Arthritis
title_full_unstemmed	Co-Delivery of Prednisolone and Curcumin in Human Serum Albumin Nanoparticles for Effective Treatment of Rheumatoid Arthritis
title_sort	co-delivery of prednisolone and curcumin in human serum albumin nanoparticles for effective treatment of rheumatoid arthritis
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/8e1d1cf13b044565b6ec65c1f396abff
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Co-Delivery of Prednisolone and Curcumin in Human Serum Albumin Nanoparticles for Effective Treatment of Rheumatoid Arthritis

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