Size-Controlled Preparation of Microsized Perfluorocarbon Emulsions as Oxygen Carriers via the Shirasu Porous Glass Membrane Emulsification Technique

Abstract

We have developed microsized perfluorocarbon (PFC) emulsions with different sizes as artificial oxygen carriers (OCs) via Shirasu porous glass membrane emulsification. Monodispersed PFC emulsions with narrow size distribution were obtained. By changing the membrane pore size, we were able to precisely control the size of emulsions and fabricate emulsions similar in size to human red blood cells. Behaviors of Pluronics with different physiochemical properties (F127, F68, P85, and P103) as surfactants were also investigated, which evidenced that the type and concentration of Pluronics have a major impact on the size of emulsions and the response to different thermal conditions. The F127-stabilized microsized PFC emulsions were stable even during autoclave sterilization. The emulsions were loaded with Ru(ddp)an oxygen-sensitive probeon their surfaces to indicate oxygen concentration. Finally, incubations with HeLa cells that show fluorescence in response to hypoxia cultured in 2D and 3D suggested promising potential of our emulsions for OCs.

Bioinspired Perfluorocarbon‐Based Oxygen Carriers with Concave Shape and Deformable Shell

“…By using different membrane pore diameters, we controlled the size of the DFCs in the size range of these circulating blood cells. In addition to previous research [24,25] including ours, [16,26] the size of emulsions and pore size showed a proportional relationship. Based on this size control of DFCs, precise shell thickness control was achieved (Figure S4, Supporting Information).…”

“…[26] The desirable size was similar to that of the hRBCs. Size control was achieved via the homogeneous pore size distribution of SPG membranes [16,[24][25][26] (Figure S2, Supporting Information). By using different membrane pore diameters, we controlled the size of the DFCs in the size range of these circulating blood cells.…”

“…[5] PFCs have several excellent properties such as chemical and heat stability, inertness, and low cost. To date, a variety of PFC-based OCs has been suggested, including PFC-encapsulated emulsions [5,16] and coreshell particles. [12][13][14] Moreover, PFC-based OCs are reported to be utilized for various medical applications such as photodynamic therapy [12,15] or radiotherapy [13] for cancer treatment, as ultrasound contrast agents, [14] for oxygenation when regenerating tissues during a perfusion culture process, [9] or as oxygen release scaffold for tissue engineering.…”

“…Note that SPG membrane emulsification [24,25] was uniquely chosen for cDFC preparation because of its precise size controllability in accordance with our previous research. [16,26] Finally, their mechanical properties, permeation properties through vascular capillary-mimicking microchannels, and oxygen delivery function to cultured cells were studied.…”

Nanoenabled Tumor Oxygenation Strategies for Overcoming Hypoxia-Associated Immunosuppression

“…O 2 molecules were dissolved in PFCs by a weak intermolecular van der Waals force, and the O 2 loading or release was passively decided by the O 2 partial pressures in certain physiological environments. , Although the PFC maintains a high O 2 solubility, its O 2 release efficiency is low due to the diffusion pattern associated with the O 2 concentration gradient. Besides, the clinical application of PFC has also been limited by its poor solubility in water and rapid metabolism. , To circumvent these problems, a variety of nanoperfluorocarbons (nano-PFCs) have been established by formulating PFCs into nanocarriers. In these nano-PFCs, O 2 could be timely released in response to external stimulus such as acidic pH or laser irradiation.…”