Abstract

To resolve problems of long treatment durations and frequent administration of the antifungal agent terbinafine (TB), solid lipid nanoparticles (SLNs) with the ability to load lipophilic drugs and nanosize were developed. The SLNs were manufactured by a microemulsion technique in which glyceryl monostearate (GMS), glyceryl behenate (Compritol® 888; Gattefossé), and glyceryl palmitostearate (Precirol® ATO 5; Gattefossé) were used as the solid lipid phases, Tween® and Cremophor® series as the surfactants, and propylene glycol as the cosurfactant to construct ternary phase diagrams. The skin of nude mice was used as a barrier membrane, and penetration levels of TB of the designed formulations and a commercial product, Lamisil® Once™ (Novartis Pharmaceuticals), in the stratum corneum (SC), viable epidermis, and dermis were measured; particle sizes were determined as an indicator of stability. The optimal SLN system contained a 50% water phase. The addition of ethanol or etchants had no significant effect on enhancing the amount of TB that penetrated the skin layers, but it was enhanced by increasing the percentage of the lipid phase. Furthermore, the combination of GMS and Compritol® 888 was able to increase the stable amount of TB that penetrated all skin layers. For the ACP1-GM1 (4% lipid phase; Compritol® 888: GMS of 1:1) formulation, the amount of TB that penetrated the SC was similar to that of Lamisil® OnceTM, whereas the amount of TB of the dermis was higher than that of Lamisil® Once™ at 12 hours, and it was almost the same as that of Lamisil® Once™ at 24 hours. It was concluded that the application of ACP1-GM1 for 12 hours might have an efficacy comparable to that of Lamisil® Once™ for 24 hours, which would resolve the practical problem of the longer administration period that is necessary for Lamisil® Once™.

Original languageEnglish
Pages (from-to)4409-4418
Number of pages10
JournalInternational Journal of Nanomedicine
Volume7
DOIs
Publication statusPublished - 2012

Fingerprint

terbinafine
Nanoparticles
Lipids
Skin
Antifungal agents
Microemulsions
Dermis
Glycols
Cornea
Drug products
Propylene
Phase diagrams
Surface active agents
Ethanol
Particle size

Keywords

  • Solid lipid nanoparticle
  • Terbinafine
  • Topical delivery system

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Organic Chemistry
  • Drug Discovery

Cite this

Development of terbinafine solid lipid nanoparticles as a topical delivery system. / Chen, Ying Chen; Liu, Der Zen; Liu, Jun Jen; Chang, Tsung Wei; Ho, Hsiu O.; Sheu, Ming Thau.

In: International Journal of Nanomedicine, Vol. 7, 2012, p. 4409-4418.

Research output: Contribution to journalArticle

@article{f496e8fffe4a4666b7265a22df7d4d8b,
title = "Development of terbinafine solid lipid nanoparticles as a topical delivery system",
abstract = "To resolve problems of long treatment durations and frequent administration of the antifungal agent terbinafine (TB), solid lipid nanoparticles (SLNs) with the ability to load lipophilic drugs and nanosize were developed. The SLNs were manufactured by a microemulsion technique in which glyceryl monostearate (GMS), glyceryl behenate (Compritol{\circledR} 888; Gattefoss{\'e}), and glyceryl palmitostearate (Precirol{\circledR} ATO 5; Gattefoss{\'e}) were used as the solid lipid phases, Tween{\circledR} and Cremophor{\circledR} series as the surfactants, and propylene glycol as the cosurfactant to construct ternary phase diagrams. The skin of nude mice was used as a barrier membrane, and penetration levels of TB of the designed formulations and a commercial product, Lamisil{\circledR} Once™ (Novartis Pharmaceuticals), in the stratum corneum (SC), viable epidermis, and dermis were measured; particle sizes were determined as an indicator of stability. The optimal SLN system contained a 50{\%} water phase. The addition of ethanol or etchants had no significant effect on enhancing the amount of TB that penetrated the skin layers, but it was enhanced by increasing the percentage of the lipid phase. Furthermore, the combination of GMS and Compritol{\circledR} 888 was able to increase the stable amount of TB that penetrated all skin layers. For the ACP1-GM1 (4{\%} lipid phase; Compritol{\circledR} 888: GMS of 1:1) formulation, the amount of TB that penetrated the SC was similar to that of Lamisil{\circledR} OnceTM, whereas the amount of TB of the dermis was higher than that of Lamisil{\circledR} Once™ at 12 hours, and it was almost the same as that of Lamisil{\circledR} Once™ at 24 hours. It was concluded that the application of ACP1-GM1 for 12 hours might have an efficacy comparable to that of Lamisil{\circledR} Once™ for 24 hours, which would resolve the practical problem of the longer administration period that is necessary for Lamisil{\circledR} Once™.",
keywords = "Solid lipid nanoparticle, Terbinafine, Topical delivery system",
author = "Chen, {Ying Chen} and Liu, {Der Zen} and Liu, {Jun Jen} and Chang, {Tsung Wei} and Ho, {Hsiu O.} and Sheu, {Ming Thau}",
year = "2012",
doi = "10.2147/IJN.S33682",
language = "English",
volume = "7",
pages = "4409--4418",
journal = "International Journal of Nanomedicine",
issn = "1176-9114",
publisher = "Dove Medical Press Ltd.",

}

TY - JOUR

T1 - Development of terbinafine solid lipid nanoparticles as a topical delivery system

AU - Chen, Ying Chen

AU - Liu, Der Zen

AU - Liu, Jun Jen

AU - Chang, Tsung Wei

AU - Ho, Hsiu O.

AU - Sheu, Ming Thau

PY - 2012

Y1 - 2012

N2 - To resolve problems of long treatment durations and frequent administration of the antifungal agent terbinafine (TB), solid lipid nanoparticles (SLNs) with the ability to load lipophilic drugs and nanosize were developed. The SLNs were manufactured by a microemulsion technique in which glyceryl monostearate (GMS), glyceryl behenate (Compritol® 888; Gattefossé), and glyceryl palmitostearate (Precirol® ATO 5; Gattefossé) were used as the solid lipid phases, Tween® and Cremophor® series as the surfactants, and propylene glycol as the cosurfactant to construct ternary phase diagrams. The skin of nude mice was used as a barrier membrane, and penetration levels of TB of the designed formulations and a commercial product, Lamisil® Once™ (Novartis Pharmaceuticals), in the stratum corneum (SC), viable epidermis, and dermis were measured; particle sizes were determined as an indicator of stability. The optimal SLN system contained a 50% water phase. The addition of ethanol or etchants had no significant effect on enhancing the amount of TB that penetrated the skin layers, but it was enhanced by increasing the percentage of the lipid phase. Furthermore, the combination of GMS and Compritol® 888 was able to increase the stable amount of TB that penetrated all skin layers. For the ACP1-GM1 (4% lipid phase; Compritol® 888: GMS of 1:1) formulation, the amount of TB that penetrated the SC was similar to that of Lamisil® OnceTM, whereas the amount of TB of the dermis was higher than that of Lamisil® Once™ at 12 hours, and it was almost the same as that of Lamisil® Once™ at 24 hours. It was concluded that the application of ACP1-GM1 for 12 hours might have an efficacy comparable to that of Lamisil® Once™ for 24 hours, which would resolve the practical problem of the longer administration period that is necessary for Lamisil® Once™.

AB - To resolve problems of long treatment durations and frequent administration of the antifungal agent terbinafine (TB), solid lipid nanoparticles (SLNs) with the ability to load lipophilic drugs and nanosize were developed. The SLNs were manufactured by a microemulsion technique in which glyceryl monostearate (GMS), glyceryl behenate (Compritol® 888; Gattefossé), and glyceryl palmitostearate (Precirol® ATO 5; Gattefossé) were used as the solid lipid phases, Tween® and Cremophor® series as the surfactants, and propylene glycol as the cosurfactant to construct ternary phase diagrams. The skin of nude mice was used as a barrier membrane, and penetration levels of TB of the designed formulations and a commercial product, Lamisil® Once™ (Novartis Pharmaceuticals), in the stratum corneum (SC), viable epidermis, and dermis were measured; particle sizes were determined as an indicator of stability. The optimal SLN system contained a 50% water phase. The addition of ethanol or etchants had no significant effect on enhancing the amount of TB that penetrated the skin layers, but it was enhanced by increasing the percentage of the lipid phase. Furthermore, the combination of GMS and Compritol® 888 was able to increase the stable amount of TB that penetrated all skin layers. For the ACP1-GM1 (4% lipid phase; Compritol® 888: GMS of 1:1) formulation, the amount of TB that penetrated the SC was similar to that of Lamisil® OnceTM, whereas the amount of TB of the dermis was higher than that of Lamisil® Once™ at 12 hours, and it was almost the same as that of Lamisil® Once™ at 24 hours. It was concluded that the application of ACP1-GM1 for 12 hours might have an efficacy comparable to that of Lamisil® Once™ for 24 hours, which would resolve the practical problem of the longer administration period that is necessary for Lamisil® Once™.

KW - Solid lipid nanoparticle

KW - Terbinafine

KW - Topical delivery system

UR - http://www.scopus.com/inward/record.url?scp=84870313897&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870313897&partnerID=8YFLogxK

U2 - 10.2147/IJN.S33682

DO - 10.2147/IJN.S33682

M3 - Article

C2 - 22923986

AN - SCOPUS:84870313897

VL - 7

SP - 4409

EP - 4418

JO - International Journal of Nanomedicine

JF - International Journal of Nanomedicine

SN - 1176-9114

ER -