Preparation of Dual-Drug Loaded Polymer-Lipid Hybrid Nanoparticles Towards the Treatment of Breast Cancer

Abstract

Breast cancer is a major health concern worldwide, and the development of effective diagnosis and treatment methods is crucial. The incidence rates for breast cancer have increased by approximately 0.5% annually since 2004, contributing to nearly one-third of all recent malignancy diagnoses. A cancer diagnosis is an important step that affects the course and treatment of the disease. However, current imaging techniques are expensive and may cause adverse effects [1]. Preparing advanced materials with unique properties for cancer diagnosis and treatment is essential for survival rate. This thesis aims to prepare drug-loaded polymer-lipid hybrid particles for breast cancer treatment via microfluidic technologies and to investigate in vitro uptake/release studies. The first part of the study aims to prepare polymer-lipid hybrid microparticles (PLHMPs) with different morphologies using a one-nozzle microfluidic system. The size, size distribution, morphology and optical properties of the prepared PLHMPs were investigated by Optical Microscope (OM), Scanning Electron Microscope (SEM) and Polarized Light Microscope (POM). Particles with different Janus morphologies were prepared with bi-compartmental, dumbbell and snowman morphologies by varying the polymer-lipid ratio, lipid type, surfactant type and concentration used to prepare PLHMPs. In addition to the prepared Janus PLHMPs, birefringent PLHMPs capable of rotational and translational movements were prepared by using different lipids in the particles. These particles were loaded with magnetic nanoparticles and made responsive to a magnetic field. PLHMPs prepared by microfluidic technology with different polymer-lipid compositions were functionalized for different biomedical applications as stimuli responsive. Polymer-lipid hybrid nanoparticles (PLHNPs) were prepared from different stimuli-responsive PLHMPs under selected conditions with an aluminium-glass (Al-Gl) microfluidic system designed by examining particle compositions and conditions with suitable morphology as a drug delivery system. PLHNPs with a size of 100-200 nm were prepared via microfluidic technology. Resveratrol (RES) and rhodamine-B (Rh-B) were used as model drug molecules to evaluate the drug uptake/release capacity of polymer-lipid hybrid particles prepared with desired properties for breast cancer treatment. Drug uptake/release capacities for the particles used were analyzed using UV-vis spectroscopy. Then the polymer-lipid hybrid particles were prepared for the first time in the literature with a one-nozzle microfluidic system with different stimuli. In addition, the magnetic nanoparticles added to the PLHMP structure have resulted in a new generation of hybrid structures that can be used for diagnostic and therapeutic purposes. Smart PLHMPs with different compositions and magnetic and optical stimuli were prepared with the same microfluidic system for the first time in the literature. At the same time, as an alternative to polymer-based microfluidic systems for nanoparticle synthesis for the first time in the literature, PLHNPs of 100 nm in size were prepared with high monodispersity (PDI > 0.1) with a microfluidic system prepared from cheap and chemically inert Al-Gl material.