Article pubs.acs.org/Langmuir
Microfluidics Fabrication of Monodisperse Biocompatible Phospholipid Vesicles for Encapsulation and Delivery of Hydrophilic Drug or Active Compound Feng Kong,†,§,∥ Xu Zhang,‡,§ and Mingtan Hai*,†,‡ †
School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, People’s Republic of China ‡ School of Engineering and Applied Science, Harvard University, Cambridge, Massachusetts 02138, United States S Supporting Information *
ABSTRACT: We encapsulate the hydrophilic anti-cancer drug doxurubicin hydrochloride (DOX) with about 94% drug encapsulation efficiency, either alone or with nanomagnetite, in monodisperse biocompatible phospholipid vesicles. Glass capillary microfluidics is used to generate monodisperse water in oil in water (w/o/w) double-emulsion templates with a core−shell structure by using a mixture of liquid unsaturated phospholipids and powdered saturated phospholipid. This combination would overcome the low transition temperature of unsaturated powdered phospholipid and the solubility limitation of saturated phospholipid, as well as improving the fabrication of stable monodisperse phospholipid vesicles. The double-emulsion droplet is controlled from 50 to 200 μm according to different flow rates, and the final phospholipid vesicles are retained after a solvent removal step by dewetting. DOX-loaded phospholipid vesicles show sustained release compared with free DOX water solution. The in vitro cell viability of 100 μg/mL phospholipid vesicles on HeLa or MCF-7 cells after 24 h incubation at 310 K is above 90%, confirming the excellent biocompatibility of the phospholipid vesicles. These biocompatible phospholipid vesicles are promising oral drug delivery vehicles for biomedical applications and magnetic resonance imaging contrast agents for biomedical diagnosis.
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INTRODUCTION Phospholipid vesicles, also known as liposomes, are phospholipid bilayer membranes that surround aqueous compartments; these vesicles can encapsulate hydrophilic active compounds such as drugs, cosmetics, proteins, or genes. They are used extensively as delivery vehicles in the pharmaceutics, food, or cosmetics industries,1−5 mainly because of their biocompatibility and biodegradability.6,7 In particular, liposomes can be used to encapsulate hydrophilic anti-cancer drugs, such as doxorubicin hydrochloride (DOX), one of the most effective drugs for breast cancer treatment. DOX has severe adverse effects,8 and the encapsulation of DOX within liposomes can minimize side effects effectively.1,9 Efficient delivery of drug often entails a specific vehicle for encapsulation and release. Nanosized carriers or nanoparticles are practical drug delivery systems.10−18 Nevertheless, the drug loading capacity in the nanocarrier-based delivery system is rather low, as the carriers are usually the major part with weight far bigger than the drugs (generally more than 80%).19,20 In addition, the presence of drug carriers would increase systemic toxicity of drug formulation.21 However, many challenges remain in the development of effective oral drug delivery vehicles for a preferred cancer treatment due to its convenience, patient compliance, and cost-effectiveness. The oral bioavailability of DOX is very low (
