DEVELOPMENTS OF LIPID-BASED NANOPARTICLES FOR THERAPEUTIC DRUG DELIVERY

DEVELOPMENTS OF LIPID-BASED NANOPARTICLES FOR THERAPEUTIC DRUG DELIVERY

Bibliographic Details
Main Author: Zhang, Mengzi
Language:English
Published: The Ohio State University / OhioLINK 2014
Subjects:
Cellular Biology
Pharmaceuticals
Molecular Biology
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1417025932
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu14170259322021-08-03T06:28:23Z DEVELOPMENTS OF LIPID-BASED NANOPARTICLES FOR THERAPEUTIC DRUG DELIVERY Zhang, Mengzi Cellular Biology Pharmaceuticals Molecular Biology The objective of this dissertation is to develop lipid-based nanoparticle systems for therapeutic oligonucleotide-based therapy and chemotherapy delivery. Oligonucleotide-based therapy is highly promising because they target levels of corresponding downstream proteins and regulate multiple cellular pathways. However, clinical application of oligonucleotide-based therapy is limited due to the stability of oligonucleotide in biological environment and lack of efficient delivery system to target tissue. Chapter 2 established a novel lipid-based nanoparticle system for targeted delivery of oligonucleotide-based therapy selectively to hepatocellular carcinoma (HCC) cells. The novelty of this delivery system was the combination of a synthesized ligand for liver-targeted delivery and a hydrophobic peptide for improved endosomal escape. The in vitro and in vivo evaluations of this delivery system showed favorable physiochemical properties, improved delivery efficiency and superiority over commercial delivery agent, suggesting its potential application in oligonucleotide-based therapy in liver disease. Chemotherapy is one of the major categories for current cancer treatments to prolong life or reduce symptoms. Conventional chemotherapeutic drugs in cancer therapies are often act by killing highly dividing cells, which also harm normal cells and cause severe side effects to normal organs. In order to maximize the treatment efficacy while minimizing side effects, the development of efficient delivery systems is urgently needed. In Chapter 3, a liver-targeted lipid-based delivery system was developed and evaluated for doxorubicin delivery (Lac-L-DOX). This Lac-L-DOX exhibited preferential uptake by targeted tissue and enhanced therapeutic efficacy than non-targeted vehicles. In Chapter 4, a novel lyophilized liposomal formulation of bortezomib was successfully designed and developed. This formulation exhibited excellent stability and improved efficacy. To the best of our knowledge, this is the first study of formulating bortezomib into lipid-based nanoparticles to greatly enhance the therapeutic efficacy and reduce non-specific tissue toxicity. In conclusion, the development of lipid-based nanoparticles for therapeutic oligonucleotide-based therapy and chemotherapy delivery would provide an insight to novel therapeutic strategy for the efficient management of cancer treatments. 2014 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1417025932 http://rave.ohiolink.edu/etdc/view?acc_num=osu1417025932 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Cellular Biology
Pharmaceuticals
Molecular Biology
spellingShingle Cellular Biology
Pharmaceuticals
Molecular Biology
Zhang, Mengzi
DEVELOPMENTS OF LIPID-BASED NANOPARTICLES FOR THERAPEUTIC DRUG DELIVERY
author Zhang, Mengzi
author_facet Zhang, Mengzi
author_sort Zhang, Mengzi
title DEVELOPMENTS OF LIPID-BASED NANOPARTICLES FOR THERAPEUTIC DRUG DELIVERY
title_short DEVELOPMENTS OF LIPID-BASED NANOPARTICLES FOR THERAPEUTIC DRUG DELIVERY
title_full DEVELOPMENTS OF LIPID-BASED NANOPARTICLES FOR THERAPEUTIC DRUG DELIVERY
title_fullStr DEVELOPMENTS OF LIPID-BASED NANOPARTICLES FOR THERAPEUTIC DRUG DELIVERY
title_full_unstemmed DEVELOPMENTS OF LIPID-BASED NANOPARTICLES FOR THERAPEUTIC DRUG DELIVERY
title_sort developments of lipid-based nanoparticles for therapeutic drug delivery
publisher The Ohio State University / OhioLINK
publishDate 2014
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1417025932
work_keys_str_mv AT zhangmengzi developmentsoflipidbasednanoparticlesfortherapeuticdrugdelivery
_version_ 1719437415329824768

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