Flash NanoComplexation (FNC) as a Scalable and Tunable Platform for Anti-Cancer Drug/Gene Delivery
Embargo until
2022-05-01
Date
2018-05-15
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Johns Hopkins University
Abstract
Nanoparticles (NPs) have been extensively investigated as drug carriers for the delivery of therapeutic agents and have demonstrated promising results in cancer treatment. However, the traditional NP preparation methods such as co-precipitation, rapid injection and thin-film hydration involve complicated fabrication and purification processes, which significantly hinder their clinical translations. A novel NP fabrication method termed flash nanocomplexation (FNC) has been recently developed in our lab, which adopts a designed Multi-Inlet Vortex Mixer (MIVM) device together with flow rate-controllable pumps to achieve rapid and complete mixing before precipitation or complexation to form NPs. This method allows the continuous and tunable production of NPs and has the potential for fast clinical translation. This thesis investigated the capacity of using FNC method to fabricate anti-cancer drug loaded NPs as well as lipid-based DNA NPs in a controllable manner. Curcumin (Cur)-loaded NPs with different loading levels (11%, 22% and 35%) were first fabricated using FNC method. Distinguished from previously reported Cur NPs, this NP formulation was assembled through hydrogen bond interactions. The FNC-fabricated Cur NPs were then characterized by particle size, zeta potential, in vitro stability, cellular uptake, and cytotoxicity. The effect of drug loading level on cellular uptake and cytoxicity was also investigated. Additionally, the ability of using FNC method to produce lipid-based NPs (lipopolyplexes and lipoplexes) in a scalable and tunable process for potential oral delivery of therapeutic DNA molecules was also studied. The particle size, size distribution, particle structure and loading efficiency of the FNC-fabricated DNA NPs were compared with the NPs prepared by traditional methods. The stability of the FNC-prepared NPs in different gastrointestinal pH environments (pH= 2.5, 6.5, and 7.4) was examined in vitro. Cellular uptake and transfection efficiency of the different lipid-based NPs were measured in three cell lines (PC3, MDA-MB-231, and Caco-2) with or without mucus-simulating condition. This study demonstrated the advantages of using FNC method to fabricate NPs in a scalable and tunable manner for anti-cancer drug/gene delivery.
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Keywords
nanotechnology, cancer, flash nanocomplexation