Paclitaxel-loaded hyaluronan solid nanoemulsions for enhanced treatment efficacy in ovarian cancer

Joo-Eun Kim, Young-Joon Park College of Pharmacy, Ajou University, Suwon City, Republic of Korea Abstract: Paclitaxel-loaded hyaluronan solid nanoemulsions (PTX-HSNs) were successfully fabricated for the delivery of PTX to improve ovarian cancer treatment via active tumor targeting. PTX-HSNs were...

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Autores principales:	Kim JE, Park YJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Paclitaxel Hyaluronan solid-nanoemulsion Targeting MTD Efficacy. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c03c7544397e4e01b11a1f85e9513191
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spelling	oai:doaj.org-article:c03c7544397e4e01b11a1f85e95131912021-12-02T02:04:24ZPaclitaxel-loaded hyaluronan solid nanoemulsions for enhanced treatment efficacy in ovarian cancer1178-2013https://doaj.org/article/c03c7544397e4e01b11a1f85e95131912017-01-01T00:00:00Zhttps://www.dovepress.com/paclitaxel-loaded-hyaluronan-solid-nanoemulsions-for-enhanced-treatmen-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Joo-Eun Kim, Young-Joon Park College of Pharmacy, Ajou University, Suwon City, Republic of Korea Abstract: Paclitaxel-loaded hyaluronan solid nanoemulsions (PTX-HSNs) were successfully fabricated for the delivery of PTX to improve ovarian cancer treatment via active tumor targeting. PTX-HSNs were fabricated using high-pressure homogenization with a microfluidizer and were lyophilized with D-mannitol. Hyaluronan was coated on the outside of the PTX-HSN sphere. The mean size of the PTX-HSNs was maintained less than 100 nm, with a relatively narrow size distribution. The PTX loading content was 3 mg/mL, and encapsulation efficiency (EE) was close to 100%. In vitro cell affinity studies using SK-OV-3 (cluster of differentiation 44 [CD44+]) and OVCAR-3 (CD44-) cells showed that PTX-HSN had a targeting capability hundredfold higher than that of PTX-loaded solid nanoemulsions (PTX-SNs) without hyaluronan. Further, the in vitro PTX release by PTX-SNs and PTX-HSNs lasted more than 6 days without showing a release burst, which was more sustained than that of Taxol®, suggesting a more constant effect on cancer cells at the tumor site than was observed for Taxol. The in vivo toxicity, in vivo antitumor effects, and pharmacokinetics of PTX-HSNs and Taxol were evaluated in nude mice and rats. The maximum tolerated dose (MTD) for PTX-HSNs, PTX-SNs, and Taxol was determined by measuring changes in clinical symptoms after administering 20–50 mg/kg PTX via the caudal vein. The MTD of PTX-HSNs had a dosing capacity greater than 50 mg PTX/kg, which was 2.5-fold higher than that of Taxol when administered as a PTX injection. In vivo, PTX-HSN treatment effectively inhibited tumor growth and showed less toxicity in tumor-transplanted mice compared to that observed for Taxol treatments. The pharmacokinetic parameters of PTX-HSNs were more desirable than those of Taxol. After PTX-HSN treatment, the circulation time of PTX was prolonged and retention of PTX in ovarian tumor tissues increased. Therefore, PTX-HSN is a highly effective nanosystem with a high MTD for delivering PTX to ovarian cancers characterized by CD44 overexpression, enhanced active tumor targeting, and low toxicity. Keywords: paclitaxel, hyaluronan solid nanoemulsion, targeting, MTD, efficacyKim JEPark YJDove Medical PressarticlePaclitaxelHyaluronan solid-nanoemulsionTargetingMTDEfficacy.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 645-658 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Paclitaxel Hyaluronan solid-nanoemulsion Targeting MTD Efficacy. Medicine (General) R5-920
spellingShingle	Paclitaxel Hyaluronan solid-nanoemulsion Targeting MTD Efficacy. Medicine (General) R5-920 Kim JE Park YJ Paclitaxel-loaded hyaluronan solid nanoemulsions for enhanced treatment efficacy in ovarian cancer
description	Joo-Eun Kim, Young-Joon Park College of Pharmacy, Ajou University, Suwon City, Republic of Korea Abstract: Paclitaxel-loaded hyaluronan solid nanoemulsions (PTX-HSNs) were successfully fabricated for the delivery of PTX to improve ovarian cancer treatment via active tumor targeting. PTX-HSNs were fabricated using high-pressure homogenization with a microfluidizer and were lyophilized with D-mannitol. Hyaluronan was coated on the outside of the PTX-HSN sphere. The mean size of the PTX-HSNs was maintained less than 100 nm, with a relatively narrow size distribution. The PTX loading content was 3 mg/mL, and encapsulation efficiency (EE) was close to 100%. In vitro cell affinity studies using SK-OV-3 (cluster of differentiation 44 [CD44+]) and OVCAR-3 (CD44-) cells showed that PTX-HSN had a targeting capability hundredfold higher than that of PTX-loaded solid nanoemulsions (PTX-SNs) without hyaluronan. Further, the in vitro PTX release by PTX-SNs and PTX-HSNs lasted more than 6 days without showing a release burst, which was more sustained than that of Taxol®, suggesting a more constant effect on cancer cells at the tumor site than was observed for Taxol. The in vivo toxicity, in vivo antitumor effects, and pharmacokinetics of PTX-HSNs and Taxol were evaluated in nude mice and rats. The maximum tolerated dose (MTD) for PTX-HSNs, PTX-SNs, and Taxol was determined by measuring changes in clinical symptoms after administering 20–50 mg/kg PTX via the caudal vein. The MTD of PTX-HSNs had a dosing capacity greater than 50 mg PTX/kg, which was 2.5-fold higher than that of Taxol when administered as a PTX injection. In vivo, PTX-HSN treatment effectively inhibited tumor growth and showed less toxicity in tumor-transplanted mice compared to that observed for Taxol treatments. The pharmacokinetic parameters of PTX-HSNs were more desirable than those of Taxol. After PTX-HSN treatment, the circulation time of PTX was prolonged and retention of PTX in ovarian tumor tissues increased. Therefore, PTX-HSN is a highly effective nanosystem with a high MTD for delivering PTX to ovarian cancers characterized by CD44 overexpression, enhanced active tumor targeting, and low toxicity. Keywords: paclitaxel, hyaluronan solid nanoemulsion, targeting, MTD, efficacy
format	article
author	Kim JE Park YJ
author_facet	Kim JE Park YJ
author_sort	Kim JE
title	Paclitaxel-loaded hyaluronan solid nanoemulsions for enhanced treatment efficacy in ovarian cancer
title_short	Paclitaxel-loaded hyaluronan solid nanoemulsions for enhanced treatment efficacy in ovarian cancer
title_full	Paclitaxel-loaded hyaluronan solid nanoemulsions for enhanced treatment efficacy in ovarian cancer
title_fullStr	Paclitaxel-loaded hyaluronan solid nanoemulsions for enhanced treatment efficacy in ovarian cancer
title_full_unstemmed	Paclitaxel-loaded hyaluronan solid nanoemulsions for enhanced treatment efficacy in ovarian cancer
title_sort	paclitaxel-loaded hyaluronan solid nanoemulsions for enhanced treatment efficacy in ovarian cancer
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/c03c7544397e4e01b11a1f85e9513191
work_keys_str_mv	AT kimje paclitaxelloadedhyaluronansolidnanoemulsionsforenhancedtreatmentefficacyinovariancancer AT parkyj paclitaxelloadedhyaluronansolidnanoemulsionsforenhancedtreatmentefficacyinovariancancer
_version_	1718402732105138176

Paclitaxel-loaded hyaluronan solid nanoemulsions for enhanced treatment efficacy in ovarian cancer

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