Graduation Semester and Year

2010

Language

English

Document Type

Thesis

Degree Name

Master of Science in Biomedical Engineering

Department

Bioengineering

First Advisor

Liping Tang

Abstract

Melanoma skin cancer is the most dangerous form of skin cancer and the major cause of deaths related to skin cancer worldwide. Conventional chemotherapeutic treatment is not very effective and faces many problems such as low response rate, development of multidrug resistance, and severe side effects. In order to address these limitations and improve melanoma treatment efficacy, development of a multifunctional nanoparticulate drug delivery system is desired. Thus, we aimed towards the development of magnetic-based core-shell nanoparticles (MBCS NPs) for dual drug release and dual targeting of melanoma tumors. The synthesized nanoparticles were composed of Poly (Lactic-co-glycolic acid) (PLGA) particle core embedded with functionalized magnetite nanoparticles and a thermo-responsive polymer (PNIPAAm-AAm-AH) shell. The nanoparticles were further conjugated with therapeutic targeting peptide GRGDS, which were specifically bound to skin cancer cells, to increase selectivity and efficacy towards melanoma treatment. The nanoparticles were 300-350 nm in size, which was confirmed by TEM and DLS techniques. Their saturation magnetization value measured using SQUID magnetometer was 15.65 emu/g. The nanoparticles exhibited no cytotoxicity towards human dermal fibroblast cells up to a concentration of 500 µg/ml, whereas the optimum nanoparticle concentration uptaken by melanoma cancer (B16F10) cells was about 300 µg/ml. A sustained Curcumin release from the core of the nanoparticles was observed until 25 days, and a burst Doxorubicin release from the thermo-sensitive shell of the nanoparticles at 41˚C was observed over a period of seven days. The developed nanoparticles were also effective for use as contrast agents for MRI. The in vitro pharmacological studies indicated the effectiveness of the MBCS NPs loaded with two drugs. The recruitment of the GRGDS-conjugated MBCS NPs at the tumor site was also observed in preliminary in vivo studies using animal (mice) models. These results suggest that our nanoparticles can be used as drug carriers to deliver two types of drugs and to specifically deliver these chemotherapeutic reagents to melanoma skin cancer only in order to increase their clinical efficiency and to reduce their severe side effects.

Disciplines

Biomedical Engineering and Bioengineering | Engineering

Comments

Degree granted by The University of Texas at Arlington

Download

Share

COinS