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Integration of PEG 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors

Introduction: Kolliphor(®) EL (K-EL) is among the most useful surfactants in the preparation of emulsions. However, it is associated with low hydrophobic drug loading in the resulting emulsified formulation. Methods: In this study, a formulation for intranasal administration of butylidenephthalide (...

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Autores principales: Chen, Yu-Shuan, Chiu, Yu-Han, Li, Yuan-Sheng, Lin, En-Yi, Hsieh, Dean-Kuo, Lee, Chia-Hung, Huang, Mao-Hsuan, Chuang, Hong-Meng, Lin, Shinn-Zong, Harn, Horng-Jyh, Chiou, Tzyy-Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530554/
https://www.ncbi.nlm.nih.gov/pubmed/31190814
http://dx.doi.org/10.2147/IJN.S193617
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author Chen, Yu-Shuan
Chiu, Yu-Han
Li, Yuan-Sheng
Lin, En-Yi
Hsieh, Dean-Kuo
Lee, Chia-Hung
Huang, Mao-Hsuan
Chuang, Hong-Meng
Lin, Shinn-Zong
Harn, Horng-Jyh
Chiou, Tzyy-Wen
author_facet Chen, Yu-Shuan
Chiu, Yu-Han
Li, Yuan-Sheng
Lin, En-Yi
Hsieh, Dean-Kuo
Lee, Chia-Hung
Huang, Mao-Hsuan
Chuang, Hong-Meng
Lin, Shinn-Zong
Harn, Horng-Jyh
Chiou, Tzyy-Wen
author_sort Chen, Yu-Shuan
collection PubMed
description Introduction: Kolliphor(®) EL (K-EL) is among the most useful surfactants in the preparation of emulsions. However, it is associated with low hydrophobic drug loading in the resulting emulsified formulation. Methods: In this study, a formulation for intranasal administration of butylidenephthalide (Bdph), a candidate drug against glioblastoma (GBM), was prepared. Physical characteristics of the formulation such as particle size, zeta potential, conductivity, and viscosity were assessed, as well as its cytotoxicity and permeability, in order to optimize the formulation and improve its drug loading capacity. Results: The optimized formulation involved the integration of polyethylene glycol 400 (PEG 400) in K-EL to encapsulate Bdph dissolved in dimethyl sulfoxide (DMSO), and it exhibited higher drug loading capacity and drug solubility in water than the old formulation, which did not contain PEG 400. Incorporation of PEG 400 as a co-surfactant increased Bdph loading capacity to up to 50% (v/v), even in formulations using Kolliphor(®) HS 15 (K-HS15) as a surfactant, which is less compatible with Bdph than K-EL. The optimized Bdph formulation presented 5- and 2.5-fold higher permeability and cytotoxicity, respectively, in human GBM than stock Bdph. This could be attributed to the high drug loading capacity and the high polarity index due to DMSO, which increases the compatibility between the drug and the cell. Rats bearing a brain glioma treated with 160 mg/kg intranasal emulsified Bdph had a mean survival of 37 days, which is the same survival time achieved by treatment with 320 mg/kg stock Bdph. This implies that the optimized emulsified formulation required only half the Bdph dose to achieve an efficacy similar to that of stock Bdph in the treatment of animals with malignant brain tumor.
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spelling pubmed-65305542019-06-12 Integration of PEG 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors Chen, Yu-Shuan Chiu, Yu-Han Li, Yuan-Sheng Lin, En-Yi Hsieh, Dean-Kuo Lee, Chia-Hung Huang, Mao-Hsuan Chuang, Hong-Meng Lin, Shinn-Zong Harn, Horng-Jyh Chiou, Tzyy-Wen Int J Nanomedicine Original Research Introduction: Kolliphor(®) EL (K-EL) is among the most useful surfactants in the preparation of emulsions. However, it is associated with low hydrophobic drug loading in the resulting emulsified formulation. Methods: In this study, a formulation for intranasal administration of butylidenephthalide (Bdph), a candidate drug against glioblastoma (GBM), was prepared. Physical characteristics of the formulation such as particle size, zeta potential, conductivity, and viscosity were assessed, as well as its cytotoxicity and permeability, in order to optimize the formulation and improve its drug loading capacity. Results: The optimized formulation involved the integration of polyethylene glycol 400 (PEG 400) in K-EL to encapsulate Bdph dissolved in dimethyl sulfoxide (DMSO), and it exhibited higher drug loading capacity and drug solubility in water than the old formulation, which did not contain PEG 400. Incorporation of PEG 400 as a co-surfactant increased Bdph loading capacity to up to 50% (v/v), even in formulations using Kolliphor(®) HS 15 (K-HS15) as a surfactant, which is less compatible with Bdph than K-EL. The optimized Bdph formulation presented 5- and 2.5-fold higher permeability and cytotoxicity, respectively, in human GBM than stock Bdph. This could be attributed to the high drug loading capacity and the high polarity index due to DMSO, which increases the compatibility between the drug and the cell. Rats bearing a brain glioma treated with 160 mg/kg intranasal emulsified Bdph had a mean survival of 37 days, which is the same survival time achieved by treatment with 320 mg/kg stock Bdph. This implies that the optimized emulsified formulation required only half the Bdph dose to achieve an efficacy similar to that of stock Bdph in the treatment of animals with malignant brain tumor. Dove 2019-05-16 /pmc/articles/PMC6530554/ /pubmed/31190814 http://dx.doi.org/10.2147/IJN.S193617 Text en © 2019 Chen et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Chen, Yu-Shuan
Chiu, Yu-Han
Li, Yuan-Sheng
Lin, En-Yi
Hsieh, Dean-Kuo
Lee, Chia-Hung
Huang, Mao-Hsuan
Chuang, Hong-Meng
Lin, Shinn-Zong
Harn, Horng-Jyh
Chiou, Tzyy-Wen
Integration of PEG 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors
title Integration of PEG 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors
title_full Integration of PEG 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors
title_fullStr Integration of PEG 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors
title_full_unstemmed Integration of PEG 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors
title_short Integration of PEG 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors
title_sort integration of peg 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530554/
https://www.ncbi.nlm.nih.gov/pubmed/31190814
http://dx.doi.org/10.2147/IJN.S193617
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