title: Ionic Driven Embedment of Hyaluronic Acid Coated Liposomes in Polyelectrolyte Multilayer Films for Local Therapeutic Delivery.
abstract: The ability to control the spatial distribution and temporal release of a therapeutic remains a central challenge for biomedical research. Here, we report the development and optimization of a novel substrate mediated therapeutic delivery system comprising of hyaluronic acid covalently functionalized liposomes (HALNPs) embedded into polyelectrolyte multilayer (PEM) platform via ionic stabilization. The PEM platform was constructed from sequential deposition of Poly-L-Lysine (PLL) and Poly(Sodium styrene sulfonate) (SPS) "(PLL/SPS)4.5" followed by adsorption of anionic HALNPs. An adsorption affinity assay and saturation curve illustrated the preferential HALNP deposition density for precise therapeutic loading. (PLL/SPS)2.5 capping layer on top of the deposited HALNP monolayer further facilitated complete nanoparticle immobilization, cell adhesion, and provided nanoparticle confinement for controlled linear release profiles of the nanocarrier and encapsulated cargo. To our knowledge, this is the first study to demonstrate the successful embedment of a translatable lipid based nanocarrier into a substrate that allows for temporal and spatial release of both hydrophobic and hydrophilic drugs. Specifically, we have utilized our platform to deliver chemotherapeutic drug Doxorubicin from PEM confined HALNPs. Overall, we believe the development of our HALNP embedded PEM system is significant and will catalyze the usage of substrate mediated delivery platforms in biomedical applications.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, NE, 68588.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hayward
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, NE, 68588.
authors.forename: David M
authors.initials: DM
authors.lastname: Francis
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, NE, 68588.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sis
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, NE, 68588.|Nebraska Center for Materials and Nanoscience, University of Nebraska-Lincoln, NE, 68588.|Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, NE, 68198.
authors.forename: Srivatsan
authors.initials: S
authors.lastname: Kidambi
mesh_terms: D000327:Adsorption; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000138:chemical synthesis* / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006207:Half-Life; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D007700:Kinetics; D008081:Liposomes; D053769:Nanocapsules / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D008081:Liposomes; D053769:Nanocapsules; D011108:Polymers; D004317:Doxorubicin; D006820:Hyaluronic Acid