Development of plant aromatase inhibitor nanoparticles for masculinization of zebrafish ‪(Danio rerio)‬

การพัฒนาอนุภาคนาโนที่เป็นสารยับยั้งเอนไซม์อะโรมาเทส จากพืชเพื่อทำให้เกิดลักษณะเพศผู้ในปลาม้าลาย

Name: Tanongsak Sassa-deepaeng

LCSH: Nanoscience

Classification :.DDC: 620.5

LCSH: Enzyme inhibitors

Abstract: Male fish production has been regarded as important role for aquaculture in Thailand. One of the management to contribute this growth is the monosex fingerlings production technology through aromatase inhibitory activity for fish masculinization. Therefore, the 22 Thai plants, involved inhibiting activity of aromatase including for healing breast cancer and/or ovarian cancer or clamed as testosterone booster, were extracted by using ethanol and then investigated. It was found that Oroxylum indicum L. possess highest inhibitory activity on aromatase of tilapia microsome system. Ethyl acetate fraction of O.indicum also shows the high dose-dependent cytotoxicity both in HepG2 and MCF-7. Furthermore, the data from characterization by HPLC indicated that chrysin is the major component of this fraction. However, chrysin is practically insoluble in water. To increase water solubility of chrysin, nanoparticles of chrysin were developed by using hydroxypropylbetacyclodextrin (HPβCD), poloxamer F68, poloxamer F127, polylactic-co-glycolic acid (PLGA) and bilosome system. The effect of surfactant on enhancing the solubility was also studied. It was found that, at the proper ratio of HPβCD associated with tween80, the nanoparticles of chrysin were obtained with EE%, Z-Average particle size, and poly-dispersion index (PDI) of 100%, 8.68 ± 2.24 nm and 0.04 ± 0.0, respectively. The proper ratio of poloxamer F68 associated with tween 80 was obtained with EE%, Z-Average particle size and PDI of 100%, 12.71 ± 4.10 nm and 0.14 ± 0.0, respectively. The proper ratio of poloxamer F127 associated with tween80 was obtained with %EE, Z-Average particle size and PDI of 100%, 11.74 ± 3.22 nm and 0.05 ± 0.0, respectively. It was also found that no significant difference between ethanol and acetone used as a solvent for chrysin dissolution in the preparation process. Interestingly, the three systems of these polymeric micelles revealed that the size of chrysin nanoparticle was slightly larger than that of empty micelles. At the proper ratio of PLGA (50:50) associated with tween 80, the chrysin loaded PLGA was obtained with EE%, Z-Average particle size and PDI of 56.99 ± 4.55%, 205.00 ± 59.69 nm and 0.12 ± 0.0, respectively. Additionally, it was also found that the ratio of drug to polymer play an important role in the size of the developed drug loaded micelles significantly. At proper ratio of chrysin to bile salt, cholesterol and span 80, the chrysin loaded bilosome was obtained with EE%, Z-Average particle size and PDI of 93.64 ± 2.60%, 184.70 ± 80.12 nm and 0.32 ± 0.0, respectively. The results demonstrate that the types of surfactants and the ratio of chrysin to surfactants are critical points in the size of chrysin loaded bilosome development and entrapment efficiency. However, HPβCD associated with tween 80 of chrysin at concentration of  100 ng/mL showed low toxicity on zebrafish eggs development. It can be suggested that HPβCD associated with tween 80 can delivery chrysin into the eggs and released chrysin from nanoparticle faster than the other system with cost effectiveness. Therefore, the chrysin loaded HPβCD at concentration of 10 ng/mL and 100 ng/mL were selected for study the effect of chrysin on adult female zebrafish masculinization. The overall results demonstrated that chrysin loaded HPβCD were affected to ovarian development and gross appearance of male characteristics. These results are preliminary study of the effect of natural compound entrapped into nanoparticles on masculinization in zebrafish. Further study on the in vivo study of this nanoparticles efficacy of masculinization on other fish model will be investigated.

Chiang Mai University Library

Address: Chiang Mai

Email: cmulibref@cmu.ac.th

Name: Kazuhisa Sekimizu

Role: Chairman

Name: Surachai Pikulkaew

Role: Member

Name: Siripom Okonogi

Role: Member

Name: Wasana Chaisri

Role: Member

Name: Phenphichar Wanachantararak

Role: Member

Created: 2016

Modified: 2020-01-14

Issued: 2020-01-14

วิทยานิพนธ์/Thesis

application/pdf

Th 620.5 T167D

eng

DegreeName: Doctor of Philosophy

Level: Doctoral Degree

Descipline: Nanoscience and Nanotechnology

Grantor: Chiang Mai University

©copyrights Chiang Mai University

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