A Master of Science thesis in Biomedical Engineering by Omnia A. Mohamed entitled, “Lipsome-coated metal organic frameworks as a new drug nanocarrier”, submitted in December 2019. Thesis advisor is Dr. Rana Sabouni and thesis co-advisor is Dr. Ghaleb Husseini. Soft copy is available (Thesis, Approval Signatures, Completion Certificate, and AUS Archives Consent Form).
Cancer has emerged to become one of the predominant diseases ever known to humanity, with chemotherapeutic agents as leading methods for treating it. However, this blind-sighted treatment method that targets all cells; healthy and cancerous, has led to a broad spectrum of side effects that include fatigue, hair loss, nausea and even heart problems. Although potential drug nanocarriers are currently used in the market, e.g., liposomes, yet, their drug loading capacity is still a challenging aspect limiting their usage. This work aims to investigate the development of a novel hybrid nanocarrier from liposomes and Metal-Organic Frameworks (MOFs). In this work, a successful coating of MOFs with liposomes was established by fusion during the preparation of the liposomes. The liposomal coating was verified using several techniques namely, Dynamic Light Scattering (DLS), Cryogenic transmission electron microscopy (Cryo- TEM) and zeta potential. DLS measurements showed a change in the diameter of liposomes from 150±0.82 nm to 163.1±2.16 nm for coated MOFs. Cryo -TEM also showed an increase in the diameter from 155.55 nm for Fe-BTC MOFs and 169.23 nm for coated MOFs. The zeta potential showed charge difference of unloaded, loaded and coated MOFs from a high negative value of -39.33±0.42 mv for loaded MOFs to a relatively neutral charge of 6.23±0.47 mv for coated MOFs. Low-frequency ultrasound (US) at 35 kHz was used as a stimulus to trigger drug release from coated and uncoated MOFs. The ultrasound triggered release reached up to 70% and 50% for coated and uncoated MOFs, respectively. Furthermore, comparing release profiles with and without US, showed statistically significant difference indicating that US can drastically increase the drug release. The effect of US on MOFs structure in terms of crystallinity and composition was analyzed via Fourier Transform Infrared (FTIR) and X-ray powder diffraction (XRD). The FTIR patterns showed a significant change in some of the pore bonds, thus indicating that US alters some pores in the MOFs. The XRD patterns showed that the ultrasound maintained the crystallinity of the MOFs. Further modelling of the release kinetics with ultrasound for both coated and uncoated MOFs was conducted.