Abstract

Lung cancer is the deadliest solid tumor, leading to the deaths of more individuals than the combination of the three next most lethal cancers which are colon, prostate and breast cancer. According to the IARC, in 2012 lung cancer accounted for 13% (1.83 million) of cancer cases and caused 19% (1.56 million) of cancer deaths worldwide. Despite advances in surgery and drug discovery, lung cancer remains difficult to treat. This is a result of unavoidable exposure to carcinogens, poor diagnosis and the lack of targeted drug delivery platforms. The aim of this study was to develop a non-invasive, patient convenient platform for the targeted delivery of chemotherapeutic drugs to cancer in deeper lung tissue. The formulation consisted of inhalable maltodextrin (MD)-based microparticles (MPs) encapsulating chitosan (CS) nanoparticles (NPs) loaded with magnetic nanoparticles (MNPs) and a chemotherapeutic drug. Ionotropic gelation was used for CS NPs synthesis. MNPs were synthesized via hydrothermal method and they were superparamagnetic with magnetic saturation (Ms), coercivity (Hc) and remanence (Mr) of 48.4 Am2/Kg, 9.9x10-4 T and 0.5 Am2/Kg emu/g; respectively. CS NPs provided a sustained release of drug, whereas MNPs encapsulated in CS NPs were able to increase the NP drug release in response to an external magnetic field by 1.7 fold. Cell uptake studies conducted using lung cancer cells (A549) indicated that the CS NPs are rapidly uptaken, and show preferential toxicity to tumor cells in comparison to cultured fibroblasts. NPs were modified with anti-epidermal growth factor receptor antibodies and this modification showed to hinder cellular uptake of NPs. Afterwards, the prepared CS NPs and CS-MNPs were co-spray freeze dried (SFD) with MD. The prepared SFD powders had fine particle fraction (FPF ≤ 5.2 μm) of 40-42 % w/w and mass median aerodynamic diameter (MMAD) of 5-6 μm as determined by the next generation impactor (NGI). A mixture of CS NPs and CS-MNPs could be able to provide a continuous sustained release of drug, with intermittent blouses of drug in response to external stimuli; a drug profile desirable in cancer therapy. In conclusion, the targeted delivery to the lung cancer using the developed formulation seems to be a promising approach.

Department

Nanotechnology Program

Degree Name

MS in Nanotechnology

Graduation Date

2-1-2015

Submission Date

January 2015

First Advisor

Azzazy, Hassan M.E.

Committee Member 1

Afifi, gia N

Committee Member 2

Madkour, Tarek M.

Extent

118 p.

Document Type

Master's Thesis

Library of Congress Subject Heading 1

Lungs -- Cancer -- Treatment.

Library of Congress Subject Heading 2

Cancer -- Treatment.

Rights

The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy.

Institutional Review Board (IRB) Approval

Not necessary for this item

Comments

Study Abroad Grant by the American University in Cairo and Faculty Research Grant by the American University in Cairo

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