Microfluidic Synthesis of Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery
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Microfluidic Synthesis of Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery Eri A. Takami1 and Folarin Erogbogbo1 1
Biomedical, Chemical, and Materials Science Engineering Department, San Jose State
University, San Jose, CA 95192, U.S.A. ABSTRACT Lipid-polymer hybrid nanoparticles (LPHN) have great potential as drug delivery devices for treatment of serious medical issues such as cardiovascular disease, tuberculosis, and cancer. Nanoprecipitation is a commonly used method to synthesize LPHN in a low cost manner. However, this multi-step process proves to be difficult in consistently producing uniformly sized nanoparticles. Here we developed a microfluidic device that utilizes a threechannel pathway and mixer channel to synthesize uniformly sized LPHN in a controlled manner. Dynamic light scattering results of the microfluidic synthesized nanoparticles show decrease in diameter size from 140 nm to 40 nm as the Reynolds number of the channel inflow increases. Transmission electron microscopy confirms the size and morphology of the nanoparticles. Three dimensional structure of the LPHN were observed using atomic force microscopy. The production of higher quality nanoparticles using our microfluidics device can expedite the research and development process of drug delivering lipid polymer nanoparticles. INTRODUCTION In recent years, nanoparticles have gained attention in the biomedical field as vesicles for diagnosis and treatment of various diseases [1]. Lipid-polymer hybrid nanoparticles (LPHN), in particular, show potential as an efficient drug delivery device. Lipid-polymer hybrid nanoparticles bring the best of both worlds of lipid and polymer nanoparticles in terms of biocompatibility, biodegradability, and structural stability [2]. When delivered to a targeted part of the body, LPHN can permeate cell walls and elute encapsulated drugs over a defined time. These advantages can reduce the amount of administered drug necessary to treat a disease, preventing drug toxicity in a patient [3]. The process of synthesizing LPHN utilizes the lipid’s hydrophobic properties to allow self-assembly into nanoprecipitates in water [4-6]. However, consistent synthesis of uniformly sized nanoparticles is difficult with this method due to possible variation in particle monodispersity, sonication, and evaporation steps [7,8]. Microfluidics, the manipulation of fluids on a microscale level, overcomes these issues by automating the mixing process in a controlled manner [9]. Here we synthesized and characterized uniformly sized LPHN in a finely tuned fashion using a three-channel microfluidics device. EXPERIMENTAL DETAILS A three-channel microfluidic wafer was prepared through photolithography with channel dimensions matched accordingly to the microfluidic design by Kim et al [10]. The microfluidic device was molded using polydimethylsiloxane (PDMS) and was bonded onto a glass slide with plasma treatment.
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