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MAD (multiagent delivery) nanolayer: delivering multiple therapeutics from hierarchically assembled surface coatings.

ABSTRACT: We present hydrolytically degradable polymeric multilayer films that can codeliver multiple therapeutics of differing chemical characteristics (charged biomacromolecules and neutral hydrophobic small molecules) from a surface. This multiagent-delivery (MAD) nanolayer system integrates the hydrolytically degradable poly(beta-amino ester) as a structural component to control the degradation of the multilayers to release active therapeutic macromolecules as well as hydrophobic drugs imbedded within amphiphilic block copolymer micellar carriers within layer-by-layer (LbL) films, which would otherwise be difficult to include within the multilayers. By varying the anionic therapeutic agents (heparin and dextran sulfate) within the multilayer, we examine how different structural components can be used to control the release kinetics of multiple therapeutics from MAD nanolayers. Controlled release profiles and the in vitro efficacy of the MAD nanolayers in suppressing the growth of human smooth muscle cell lines were evaluated. The dual delivery of a charged macromolecular heparin and a small hydrophobic drug, paclitaxel, is found to be synergistic and beneficial toward effective therapeutic activity. Furthermore, we compared the classical dipping method that we employed here with an automated spray-LbL technique. Spray-LbL significantly facilitates film processing time while preserving the characteristic release profiles of the MAD nanolayers. With the highly versatile and tunable nature of LbL assembly, we anticipate that MAD nanolayers can provide a unique platform for delivering multiple therapeutics from macromolecules to small molecules with distinct release profiles for applications in biological and biomedical surface coatings.

SUBMITTER: Kim BS

PROVIDER: S-EPMC4001284 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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MAD (multiagent delivery) nanolayer: delivering multiple therapeutics from hierarchically assembled surface coatings.

Kim Byeong-Su BS Smith Renée C RC Poon Zhiyong Z Hammond Paula T PT

Langmuir : the ACS journal of surfaces and colloids 20091201 24

We present hydrolytically degradable polymeric multilayer films that can codeliver multiple therapeutics of differing chemical characteristics (charged biomacromolecules and neutral hydrophobic small molecules) from a surface. This multiagent-delivery (MAD) nanolayer system integrates the hydrolytically degradable poly(beta-amino ester) as a structural component to control the degradation of the multilayers to release active therapeutic macromolecules as well as hydrophobic drugs imbedded within ...[more]

PMID: 19630389

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Project description:Development of multifunctional nanostructures that can be tuned to codeliver multiple drugs and diagnostic agents to diseased tissues is of great importance. Hierarchically assembled theranostic (HAT) nanostructures based on anionic cylindrical shell cross-linked nanoparticles and cationic shell cross-linked knedel-like nanoparticles (cSCKs) have recently been developed by our group to deliver siRNA intracellularly and to undergo radiolabeling. In the current study, paclitaxel, a hydrophobic anticancer drug, and siRNA have been successfully loaded into the cylindrical and spherical components of the hierarchical assemblies, respectively. Cytotoxicity, immunotoxicity, and intracellular delivery mechanism of the HAT nanostructures and their individual components have been investigated. Decoration of nanoparticles with F3-tumor homing peptide was shown to enhance the selective cellular uptake of the spherical particles, whereas the HAT nanoassemblies underwent an interesting disassembly process in contact with either OVCAR-3 or RAW 264.7 cell lines. The HAT nanostructures were found to "stick" to the cell membrane and "trigger" the release of spherical cSCKs templated onto their surfaces intracellularly, while retaining the cylindrical part on the cell surface. Combination of paclitaxel and cell-death siRNA (siRNA that induces cell death) into the HAT nanostructures resulted in greater reduction in cell viability than siRNA complexed with Lipofectamine and the assemblies loaded with the individual drugs. In addition, a shape-dependent immunotoxicity was observed for both spherical and cylindrical nanoparticles with the latter being highly immunotoxic. Supramolecular assembly of the two nanoparticles into the HAT nanostructures significantly reduced the immunotoxicity of both cSCKs and cylinders. HAT nanostructures decorated with targeting moieties, loaded with nucleic acids, hydrophobic drugs, radiolabels, and fluorophores, with control over their toxicity, immunotoxicity, and intracellular delivery might have great potential for biomedical delivery applications.

Dataset Information

MAD (multiagent delivery) nanolayer: delivering multiple therapeutics from hierarchically assembled surface coatings.

Publications

MAD (multiagent delivery) nanolayer: delivering multiple therapeutics from hierarchically assembled surface coatings.

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