Dielectric charge injection (DCI)-enabled contactless droplet wetting modulation for droplet-surface material interchange.

HYPOTHESIS: Electrowetting-on-dielectric (EWOD) employs direct droplet-electrode contact to generate electric fields across the dielectric layer to modulate droplet wetting. Because the charged surface state drives this process, it should be possible to accomplish a contactless modulation of droplet wetting by charge injection onto the dielectric surface where a droplet is situated. EXPERIMENTS: We present our technique, dielectric charge injection (DCI), to contactlessly modulate droplet wetting via corona discharge-based physics. We study the ability of droplets on nonwetting surfaces to transition to a wetting state under DCI, quantify contact angle (CA) in relation to applied voltage, and examine reversibility under regimes with and without charge injection. The observed phenomena are applied to enable droplet-surface material interchange. FINDINGS: Using DCI, we induce wetting of a deionized water droplet on a non-wetting polydimethylsiloxane (PDMS) surface immersed in hexadecane, with tunable CA modulation based on applied voltage. Upon simple removal of the voltage and/or conductor, droplet fully recovers the initial non-wetting state. We combine these capabilities to enable droplet-surface material interchange of two modes: material deposition (droplet-to-surface) and material recovery (surface-to-droplet). DCI presents a unique strategy for contactless, reversible wetting state modulation that is simple yet powerful for applications such as integrating droplet microfluidics to mass spectrometry.

Highly-loaded protein nanocarriers prepared by Flash NanoPrecipitation with hydrophobic ion pairing.

The efficient encapsulation of therapeutic proteins into delivery vehicles, particularly without loss of function, remains a significant research hurdle. Typical liposomal formulations achieve drug loadings on the order of 3-5% and encapsulation efficiencies around 50%. We demonstrate the encapsulation of model proteins with isoelectric points above and below pH 7 into nanocarriers (NCs) with protein loadings as high as 46% and encapsulation efficiencies above 95%. This is done by combining the continuous nanofabrication process Flash NanoPrecipitation (FNP) with the technique of hydrophobic ion pairing by forming and encapsulating an ionic complex within a nanocarrier stabilized by a block copolymer surface layer. We complex and encapsulate lysozyme with two anionic hydrophobic counterions, sodium oleate and sodium dodecyl sulfate, using either a pre-formed complex or in situ pairing. The strategy successfully forms NCs ~150 nm in diameter and achieves encapsulation efficiencies over 95%. Protein release rate from the NCs in physiological conditions and the bioactivity of released lysozyme are measured, and both are found to vary with the complexing counterion and the protein/counterion ratio used during formulation. Protein release on the time scale of weeks is observed, and up to 100% bioactivity is measured from released lysozyme. 16 quaternary ammonium cationic counterions are tested to encapsulate ovalbumin in 32 formulations. Of these, 19 successfully form ~150 nm NCs with loadings up to 29% and encapsulation efficiencies up to 88%. We divide the formulations into four regimes and identify chemical factors responsible for the success or failure of a given counterion to formulate NCs with the desirable size, loading, and encapsulation efficiency. A successful ovalbumin NC formulation was then tested in vivo in a mouse nasal vaccine model and found to induce a higher titer of OVA-specific IgG than unencapsulated ovalbumin. Taken together, these findings suggest that Flash NanoPrecipitation with hydrophobic ion pairing is an attractive platform for encapsulating high molecular weight proteins into NCs. In particular, the ability to tune protein release rate by varying the counterion or protein/counterion ratio used during formulation is a useful feature.

Hydrophobic Ion Pairing of Peptide Antibiotics for Processing into Controlled Release Nanocarrier Formulations.

Nanoprecipitation of active pharmaceutical ingredients (APIs) to form nanocarriers (NCs) is an attractive method of producing formulations with improved stability and biological efficacies. However, nanoprecipitation techniques have not been demonstrated for highly soluble peptide therapeutics. We here present a model and technique to encapsulate highly water-soluble biologic APIs by manipulating API salt forms. APIs are ion paired with hydrophobic counterions to produce new API salts that exhibit altered solubilities suitable for nanoprecipitation processing. The governing rules of ion pair identity and processing conditions required for successful encapsulation are experimentally determined and assessed with theoretical models. Successful NC formation for the antibiotic polymyxin B requires hydrophobicity of the ion pair acid to be greater than logP = 2 for strong acids and greater than logP = 8 for weak acids. Oleic acid with a logP = 8, and pKa = 5, appears to be a prime candidate as an ion pair agent since it is biocompatible and forms excellent ion pair complexes. NC formation from preformed, organic soluble ion pairs is compared to in situ ion pairs where NCs are made in a single precipitation step. NC properties, such as stability and release rates, can be tuned by varying ion pair molecular structure and ion pair-to-API molar ratios. For polymyxin B, NCs ≈ 100-200 nm in size, displaying API release rates over 3 days, were produced. This work demonstrates a new approach that enables the formation of nanoparticles from previously intractable compounds.