Sustained-release nucleic acid matrix compositions
Inventors
Emanuel, Noam • Rosenfeld, Yosef
Assignees
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Publication Number
US-9616032-B2
Publication Date
2017-04-11
Expiration Date
Abstract
There are provided compositions for extended release of a nucleic acid agent, comprising a lipid-saturated matrix formed with a biodegradable polymer. Also provided are methods of producing the matrix compositions and methods for using the matrix compositions to provide controlled release of the nucleic acid agent.
Core Innovation
The invention provides a coated substrate having a matrix composition that includes a biocompatible polymer comprising a polyester, a first lipid component comprising at least one lipid having a polar group, and a second lipid component comprising at least one phospholipid having fatty acid moieties of at least 14 carbons. The matrix also includes at least one nucleic acid based agent and polyethylene glycol (PEG). When maintained in an aqueous environment, the matrix composition provides sustained and/or controlled release of the nucleic acid based agent.
The described formulations emphasize lipid-saturated, biodegradable polymer matrix compositions configured to deliver nucleic acid based agents with programmable release behavior. The release is influenced by polymer:lipid ratio, lipid composition, and PEG incubation time, and the matrix is described as substantially water-free after solvent/water removal while remaining maintained in an aqueous environment for release. The patent text further describes zero-order release kinetics thresholds and reduced burst release in the presence of PEG.
The document also describes example embodiments in which the nucleic acid release supports biological functionality, including PCR functionality of released oligonucleotides. Further embodiments describe coating of substrates and medical devices, including bone graft materials, and formation of implants or microspheres having particle sizes. The overall innovation is the combination of the specified polyester-based matrix with two defined lipid components plus PEG and nucleic acid based agent to achieve sustained and/or controlled release in an aqueous environment.
Claims Coverage
The partial content includes two independent claims. Across these independent claims, the central inventive features are (i) a coated substrate with a specified polyester–lipid–PEG matrix containing a nucleic acid based agent, and (ii) selecting the polyester from PLA, PGA, PLGA, and combinations thereof.
A coated substrate with sustained and/or controlled nucleic acid release in aqueous environment
A substrate is coated with a matrix composition comprising a biocompatible polymer comprising a polyester; a first lipid component comprising at least one lipid having a polar group; a second lipid component comprising at least one phospholipid having fatty acid moieties of at least 14 carbons; at least one nucleic acid based agent; and polyethylene glycol (PEG), wherein when maintained in an aqueous environment the matrix composition provides sustained and/or controlled release of the nucleic acid based agent.
Selecting the polyester from specific biodegradable polyesters
The coated substrate of the polyester-based matrix wherein the polyester is selected from the group consisting of PLA (polylactic acid), PGA (poly glycolic acid), PLGA (Poly (lactic co glycolic acid)) and combinations thereof.
The independent claims center on a coated substrate whose surface is covered by a polyester-containing, lipid-saturated matrix with PEG and a nucleic acid based agent to achieve sustained and/or controlled release in an aqueous environment, with a further independent refinement limited to PLA, PGA, or PLGA (or combinations).
Stated Advantages
Provides sustained and/or controlled release of the nucleic acid based agent when maintained in an aqueous environment.
Reduces burst release (as demonstrated in examples described in the provided content).
Supports prolonged and kinetically controlled ssDNA release (as described in the provided content).
Maintains PCR functionality of released oligonucleotides (as described in the provided content).
Documented Applications
Coating substrates and medical devices using the matrix composition (including bone graft materials) to provide sustained and/or controlled release in an aqueous environment.
Forming implants or microspheres comprising the matrix composition.
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