Silk fibroin-based nanoparticles drug delivery system by supercritical CO₂technology

Pao Yue-kong Library Electronic Theses Database

Silk fibroin-based nanoparticles drug delivery system by supercritical CO₂technology

 

Author: Zhao, Zheng
Title: Silk fibroin-based nanoparticles drug delivery system by supercritical CO₂technology
Degree: Ph.D.
Year: 2013
Subject: Nanostructured materials.
Drug delivery systems.
Hong Kong Polytechnic University -- Dissertations
Department: Institute of Textiles and Clothing
Pages: xxvi, 199 leaves : ill. (some col.) ; 30 cm.
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b2653079
URI: http://theses.lib.polyu.edu.hk/handle/200/7278
Abstract: Current cytotoxic chemotherapy in the field of biomedical engineering, especially cancer therapy has been limited by poor efficiency and high toxicity due to immediate drug release, non-specific tissue distribution, degradation by chemical and enzymatic hydrolysis, and low cellular uptake efficiency. The purposes of this study were to develop a silk fibroin-based nanoparticles drug delivery system by supercritical CO₂ technology to decrease the adverse side effects of the drugs and enhance drug performance. To achieve the objectives of the research, in the first part, silk fibroin (SF) nanoparticles were fabricated via solution-enhanced dispersion by supercritical CO₂ (SEDS) for the first time successfully. The influence of process parameters on particle size and SF nanoparticles formation mechanism were investigated. The results indicated that precipitation temperature, concentration and flow rate of SF solution have a positive effect, while precipitation pressure has a negative effect. The nanoparticle formation mechanism was elucidated with the formation and growth of silk fibroin nuclei in the gaseous miscible phase evolved from initial droplets generated by the liquid-liquid phase split. Secondly, to characterize silk fibroin (SF) nanoparticles and explore their application in drug delivery systems, ethanol was used to treat drug loaded SF nanoparticles for inducing water insolubility. The SF nanoparticles demonstrated excellent biocompatibility, time-dependent and concentration-dependent cellular uptake properties, and thus can be used as drug carrier. However, the drug leakage is a critical issue in the process of ethanol treatment. Thirdly, in order to overcome the disadvantages of SF nanoparticles and develop a novel SF/PPP nanoparticles drug carrier with the advantages of natural SF and synthetic PLLA-PEG-PLLA (PPP) polymer, a modified SEDS process was designed to prepare the SF/PPP composite nanoparticles. The results of biological evaluation showed that the silk fibroin can improve the property of PPP as drug carrier. SF/PPP nanoparticles possessed much better biocompatibility and can accelerate cell adhesion and internalization compared with PPP nanoparticles.
Furthermore, in order to study the application of SF/PPP nanoparticles in cancer therapy, anti-cancer drug, paclitaxel (PTX) was loaded into SF/PPP nanoparticles by the SEDS process. The resulting PTX loaded SF/PPP (PTX-SF/PPP) nanoparticles do not need induction of water solubility so that the drug loss of PTX loaded silk fibroin nanoparticles in post-treatment can be avoided. PTX-SF/PPP nanoparticle could enhance the solubility of PTX and exhibited controlled drug release property. Especially the drug release rate in PBS solution could be accelerated with decrease of the pH value from 7.4 to 6.0. This property can benefit the tumor-specific therapy due to the unique tumor environment. MTS assay demonstrated in vitro anti-tumor activity of the PTX-SF/PPP nanoparticles for MCF-7 and HePG-2 cells after one week was slightly higher than that of free PTX. In terms of the characteristics of nanoparticles, PTX-SF/PPP nanoparticles have potential application in the field of tumor therapy. Finally, in order to enhance the targeting efficiency of the SF/PPP nanoparticles to the tumor site, a tumor-specific ligand, folic acid (FA), was grafted onto the surface of the SF/PPP nanoparticles successfully by conjugation of the amino group on the silk fibroin with the carboxylic group of folic acid activated by EDC/NHS. Flow cytometric analysis showed that the FA-SF/PPP possessed a higher cellular uptake by MCF-7 tumor cell than SF/PPP nanoparticles. However, MTS assay indicated that in vitro anti-tumor activity had no significant difference between PTX-loaded FA-SF/PPP and PTX-loaded SF/PPP nanoparticles. Due to the tumor-targeted delivery, high drug load and controlled drug release property, the PTX-FA-SF/PPP nanoparticles can be utilized as an effective drug delivery system for tumor targeted therapy. In conclusion, silk fibroin-based nanoparticles drug delivery systems including SF, SF/PPP, and FA-SF/PPP nanoparticles have been developed by supercritical CO₂ technology successfully. These nanostructured drug delivery systems have potential application in the field of biomedical engineering, especially cancer therapy.

Files in this item

Files Size Format
b2653079x.pdf 8.439Mb PDF
Copyright Undertaking
As a bona fide Library user, I declare that:
  1. I will abide by the rules and legal ordinances governing copyright regarding the use of the Database.
  2. I will use the Database for the purpose of my research or private study only and not for circulation or further reproduction or any other purpose.
  3. I agree to indemnify and hold the University harmless from and against any loss, damage, cost, liability or expenses arising from copyright infringement or unauthorized usage.
By downloading any item(s) listed above, you acknowledge that you have read and understood the copyright undertaking as stated above, and agree to be bound by all of its terms.

     

Quick Search

Browse

More Information