Effect of Lauric Acid-loaded PCL-PEG-PCL Nano-sized Micelles on the Activity ofPropionibacterium Acnes

碩士 === 中原大學 === 奈米科技碩士學位學程 === 98 === Acne vulgaris is known as infection of pathogenic bacteria, Propionibacterium acnes (P. acnes). Lauric acid (LA) was found to kill P. acnes effectively. However, LA is a sparingly soluble fatty acid in water in which dimethly sulfoxide (DMSO) is used to increase...

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Main Authors: Keng-Lun Chang, 張耕綸
Other Authors: Ming-Fa Hsieh
Format: Others
Language:zh-TW
Published: 2010
Online Access:http://ndltd.ncl.edu.tw/handle/62489871140981028538
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spelling ndltd-TW-098CYCU57950082016-06-03T04:14:41Z http://ndltd.ncl.edu.tw/handle/62489871140981028538 Effect of Lauric Acid-loaded PCL-PEG-PCL Nano-sized Micelles on the Activity ofPropionibacterium Acnes PCL-PEG-PCL奈米微胞裝載月桂酸對痤瘡丙酸桿菌活性之抑制效應研究 Keng-Lun Chang 張耕綸 碩士 中原大學 奈米科技碩士學位學程 98 Acne vulgaris is known as infection of pathogenic bacteria, Propionibacterium acnes (P. acnes). Lauric acid (LA) was found to kill P. acnes effectively. However, LA is a sparingly soluble fatty acid in water in which dimethly sulfoxide (DMSO) is used to increase solubility. In this study, amphiphilic micelles encapsulating LA was developed to reduce DMSO-induced toxicity and improve bactericidal effect of LA. Poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) triblock copolymer was sythysized by ring-opening polymerization. Different molecular weights of PCL-PEG-PCL were synthesized and chararerized by 1H nuclear magnegtic resonance, Fourier transform infared spectroscopy, differential scanning calorimeter and gel permeation chromatography, respectively. The critical micelle concentration(CMC) of the micelle solution was determined by using fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene(DPH). The results of particle size analyzer and transmission electron microscopy show that the averge particles size of placebo micelles and LA-encapsulated micelles were 49.8-198.1 nm and 24.7-89.3 nm, respectively. Upon encapsulation of LA, zeta potential decreased from -3.0 ~ -9.7mV to -4.2 ~ -18.4 mV, because of depronated carboxyl group in LA. A High-performance liquid chromatography was used to quantitate LA encapsulated in the micelles, after encapsulated LA was derived with naphthacyl ester. As the results, the payload of PC50E40C50 for LA was 323.75 μg/mL which was the highest among various PCL-PEG-PCL. In addition, as the length of PCL increased, the drug loading contents decreased. The effect of LA-encapsulated micelles(micelle formulation) were compared with LA dissolved in 5% DMSO(free LA formulation). For free LA formulation, as free lauric acid dissolved in 5% DMSO, the minimum inhibitory concentration(MIC) and minimum bactericidal concentration(MBC) were 20 μg/mL and 80μg/mL, respectively. In contrasty, MIC and MBC of micelle formulation were only 10-20 μg/mL and 40-80 μg/mL, respectively. Therefore, the micelle formulation requires slightly lower LA to reach the same antibactirials effecacy of free LA formulation. The cytotoxicities of free LA formulation and micelle formulation in fibroblast and keratinocyte were conducted. It is found that micelle formulation I I I posses better biocompatibility over free LA. In summary, this study demonstrated that PCL-PEG-PCL was a potential drug carrier to encapsulate LA. It worthshile to further examine the efficacy to against the infection of P.acnes in animal study. Ming-Fa Hsieh 謝明發 2010 學位論文 ; thesis 128 zh-TW
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language zh-TW
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sources NDLTD
description 碩士 === 中原大學 === 奈米科技碩士學位學程 === 98 === Acne vulgaris is known as infection of pathogenic bacteria, Propionibacterium acnes (P. acnes). Lauric acid (LA) was found to kill P. acnes effectively. However, LA is a sparingly soluble fatty acid in water in which dimethly sulfoxide (DMSO) is used to increase solubility. In this study, amphiphilic micelles encapsulating LA was developed to reduce DMSO-induced toxicity and improve bactericidal effect of LA. Poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) triblock copolymer was sythysized by ring-opening polymerization. Different molecular weights of PCL-PEG-PCL were synthesized and chararerized by 1H nuclear magnegtic resonance, Fourier transform infared spectroscopy, differential scanning calorimeter and gel permeation chromatography, respectively. The critical micelle concentration(CMC) of the micelle solution was determined by using fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene(DPH). The results of particle size analyzer and transmission electron microscopy show that the averge particles size of placebo micelles and LA-encapsulated micelles were 49.8-198.1 nm and 24.7-89.3 nm, respectively. Upon encapsulation of LA, zeta potential decreased from -3.0 ~ -9.7mV to -4.2 ~ -18.4 mV, because of depronated carboxyl group in LA. A High-performance liquid chromatography was used to quantitate LA encapsulated in the micelles, after encapsulated LA was derived with naphthacyl ester. As the results, the payload of PC50E40C50 for LA was 323.75 μg/mL which was the highest among various PCL-PEG-PCL. In addition, as the length of PCL increased, the drug loading contents decreased. The effect of LA-encapsulated micelles(micelle formulation) were compared with LA dissolved in 5% DMSO(free LA formulation). For free LA formulation, as free lauric acid dissolved in 5% DMSO, the minimum inhibitory concentration(MIC) and minimum bactericidal concentration(MBC) were 20 μg/mL and 80μg/mL, respectively. In contrasty, MIC and MBC of micelle formulation were only 10-20 μg/mL and 40-80 μg/mL, respectively. Therefore, the micelle formulation requires slightly lower LA to reach the same antibactirials effecacy of free LA formulation. The cytotoxicities of free LA formulation and micelle formulation in fibroblast and keratinocyte were conducted. It is found that micelle formulation I I I posses better biocompatibility over free LA. In summary, this study demonstrated that PCL-PEG-PCL was a potential drug carrier to encapsulate LA. It worthshile to further examine the efficacy to against the infection of P.acnes in animal study.
author2 Ming-Fa Hsieh
author_facet Ming-Fa Hsieh
Keng-Lun Chang
張耕綸
author Keng-Lun Chang
張耕綸
spellingShingle Keng-Lun Chang
張耕綸
Effect of Lauric Acid-loaded PCL-PEG-PCL Nano-sized Micelles on the Activity ofPropionibacterium Acnes
author_sort Keng-Lun Chang
title Effect of Lauric Acid-loaded PCL-PEG-PCL Nano-sized Micelles on the Activity ofPropionibacterium Acnes
title_short Effect of Lauric Acid-loaded PCL-PEG-PCL Nano-sized Micelles on the Activity ofPropionibacterium Acnes
title_full Effect of Lauric Acid-loaded PCL-PEG-PCL Nano-sized Micelles on the Activity ofPropionibacterium Acnes
title_fullStr Effect of Lauric Acid-loaded PCL-PEG-PCL Nano-sized Micelles on the Activity ofPropionibacterium Acnes
title_full_unstemmed Effect of Lauric Acid-loaded PCL-PEG-PCL Nano-sized Micelles on the Activity ofPropionibacterium Acnes
title_sort effect of lauric acid-loaded pcl-peg-pcl nano-sized micelles on the activity ofpropionibacterium acnes
publishDate 2010
url http://ndltd.ncl.edu.tw/handle/62489871140981028538
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