A touch-and-go lipid wrapping technique in microfluidic channels for rapid fabrication of multifunctional envelope-type gene delivery nanodevices

Abstract

Multifunctional envelope-type gene delivery nanodevices (MENDs) are promising non-viral vectors for gene therapy. Though MENDs remain strong in prolonged exposure to blood circulation, have low immunogenic response, and are suitable for gene targeting, their fabrication requires labor-intensive processes. In this work, a novel approach has been developed for rapid fabrication of MENDs by a touch-and-go lipid wrapping technique in a polydimethylsiloxane (PDMS)/glass microfluidic device. The MEND was fabricated on a glass substrate by introduction of a condensed plasmid DNA core into microfluidic channels that have multiple lipid bilayer films. The principle of the MEND fabrication in the microfluidic channels is based on electrostatic interaction between the condensed plasmid DNA cores and the coated lipid bilayer films. The constructed MEND was collected off-chip and characterized by dynamic light scattering. The MEND was constructed within 5 min with a narrow size distribution centered around 200 nm diameter particles. The size of the MEND showed strong dependence on flow velocity of the condensed plasmid DNA core in the microfluidic channels, and thus, could be controlled to provide the optimal size for medical applications. This approach was also proved possible for fabrication of a MEND in multiple channels at the same time. This on-chip fabrication of the MEND was very simple, rapid, convenient, and cost-effective compared with conventional methods. Our results strongly indicated that MENDs fabricated with our microfluidic device have a good potential for medical use. Moreover, MENDs fabricated by this microfluidic device have a great potential for clinical use because the devices are autoclavable and all the fabrication steps can be completed inside closed microfluidic channels without any external contamination.

Lipid Bilayers Are Long-Lived on Solvent Cleaned Plasma-Oxidized poly(dimethyl)siloxane (ox-PDMS)

“…Although glass (silicon dioxide) surfaces are used conventionally to support phospholipid bilayers[13], oxidized poly(dimethyl)siloxane (PDMS) surfaces—due to its ability to be molded into complex topographies[11,14,15], to be formed into microfluidic channels[8,16–18], and to be mechanically deformed[19]—are attractive substrates to support phospholipid bilayers[15,20–22]. Native PDMS is hydrophobic[23–28], plasma oxidation is required to make the surface of PDMS hydrophilic and thus suitable for supporting phospholipid bilayers.…”

Towards principled design of cancer nanomedicine to accelerate clinical translation

“… Methods Nanomaterials Size (nm) [ 15 ] Nanocarrier production rate Ref. Multiple systems in parallel Polymeric nanoparticles 50–200 MPEG–PLGA (methoxyl poly-(ethylene glycol)–poly (lactic-co-glycolic acid)) 25–100 [ 277 ] Multiple channels in parallel Polymeric nanoparticles 200 DSPE-PEG (1,2-distearoylsn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000]) 4.5–84 [ 282 ] 13–150 PLGA-PEG poly (lactide-co-glycolide)-b-poly (ethylene glycol) 4.5–84 [ 274 ] 50–150 PLGA-PEG ∼ 10 [ 275 ] Using a coaxial turbulent jet mixer Lipid-polymer-metal oxide nanoparticles 25–100 PLGA-PEG 3.15 [ 281 ] Increasing flow rate Polymeric nanoparticles 100–240 for PLGA 100–240 for HPCS 70–280 for AcDX PLGA (poly (lactide-co-glycolide)); HPCS (hydrophobic chitosan); AcDX (acetalated dextran) 45.6–242.8 [ 283 ] 112.2–570 DSPE-PEG 2.4–14.4 [ 278 ] 60–450 for PLGA 70–550 for AcDX ...…”

Lipid Nanovesicles by Microfluidics: Manipulation, Synthesis, and Drug Delivery

“…These LNPs showed enhanced circulation stability, increased encapsulation efficiency, and improved antitumor effect against a multidrug resistant tumor model. Another microfluidic method for making LNPs was a touch and go technique which wrapped the plasmid DNA core with the lipid film through charge and hydrophobic interactions . The generated LNPs had a better homogeneity than bulk methods.…”