Combining the positive characteristics of both liposomes and polymeric nanoparticles into a single platform, lipid-polymer hybrid nanoparticles (LPNPs) enhance the loading ability and controlled release of hydrophobic compounds like polymer NPs, while maintaining excellent serum stability of lipid NPs, holding great promise as a delivery vehicle for various medical applications. In this proposed study, we use PLGA (poly(lactic-co-glycolic acid)), an FDA approved, biodegradable and biocompatible co-polymer as the core material encased in a PEGylated lipid shell to increase the LPNP half life in blood circulation. LPNP is comprised of three distinct functional components: (i) a hydrophobic PLGA core that incorporates poorly water-soluble drugs with high loading yields; (ii) a lipid layer that encapsulates the drug-loaded PLGA core and promotes drug retention; and (iii) a hydrophilic layer outside the lipid shell to enhance NP stability in blood circulation.
Controlled microfluidic synthesis of polymeric NPs has exhibited the ability to regulate single-step nanoprecipitation for tunable NP assembly using lateral diffusive dispersion across the interface between streams flowing alongside in microfluidics to synthesize polymeric NPs. Since the mixing in these systems relies largely on molecular diffusion across concentration gradients, the residence time for the precursors is usually long (e.g., on the order of seconds to a minute) in viscous flow at low Reynolds number (Re). A common technique to shorten mixing times is to reduce diffusion length scales by convective mixing, which increases the interfacial surface area between the fluids. A variety of mixing principles for systems with Re in a range of 1~100 have been reported in recent years. Convective mixing approaches in microfluidics resulted in better production of homogeneous polymeric NPs with higher production rate and narrower size distribution than diffusive mixing-based synthesis methods. Recent microfluidic attempts including our approaches continue to demonstrate enhanced production rates up to hundreds of milligrams per hour compared to those (a few mg/h) of previous microfluidic methods.
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Kim Y*, Lobatto ME*, Kawahara T, Lee Chung B, Mieszawska AJ, Sanchez-Gaytan BL, Fay F, Senders M, Calcagno C, Becraft J, Saung MT, Gordon RE, Ma M, Farokhzad OC, Fayad ZA, Mulder WJM, and Langer R, Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis (2014) Proceedings of the National Academy of Sciences (PNAS) 111 (3): 1078-1083 (Link).
Mieszawska A, Kim Y, Gianella A, van Rooy I, Priem B, Labarre MP, Ozcan C, Cormode DP, Petrov A, Langer R, Farokhzad OC, Fayad ZA, and Mulder WJM, Synthesis of polymer-lipid nanoparticles for image-guided delivery of dual modality therapy (2013) Bioconjugate Chemistry 24 (9): 1429-1434 (Link).
Kim Y, Lee Chung B, Ma M, Mulder WJM, Fayad ZA, Farokhzad OC, and Langer R, Mass production and size control of lipid-polymer hybrid nanoparticles through controlled microvortices (2012) Nano Letters 12 (7): 3587–3591 (Link).