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Asymmetric biofunctional silyl monomers and particles thereof as prodrugs and delivery vehicles for pharmaceutical, chemical and biological agents

a technology of biofunctional silyl monomers and prodrugs, applied in the direction of dna/rna fragmentation, silicon organic compounds, powder delivery, etc., can solve the problems of high toxicity to normal tissues, cellular delivery of various therapeutic compounds such as chemotherapeutic agents, and high restriction of the trafficking of many compounds into living cells

Inactive Publication Date: 2013-08-08
DESIMONE JOSEPH M +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes monomers that can be used to modify agents with pharmaceutical, chemical, and biological properties. These monomers can be attached to delivery vehicles, such as particles, to deliver the agents to specific targets or areas. The modified agents have improved properties, such as solubility, stability, and targeting. Overall, this patent provides a way to create customizable agents for use in various applications.

Problems solved by technology

The cellular delivery of various therapeutic compounds, such as chemotherapeutic agents, is usually compromised by two limitations.
First, the selectivity of a number of therapeutic agents is often low, resulting in high toxicity to normal tissues.
Secondly, the trafficking of many compounds into living cells is highly restricted by the complex membrane systems of the cell.
The problems mentioned above are not adequately addressed by existing delivery vehicles or compositions.

Method used

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  • Asymmetric biofunctional silyl monomers and particles thereof as prodrugs and delivery vehicles for pharmaceutical, chemical and biological agents
  • Asymmetric biofunctional silyl monomers and particles thereof as prodrugs and delivery vehicles for pharmaceutical, chemical and biological agents
  • Asymmetric biofunctional silyl monomers and particles thereof as prodrugs and delivery vehicles for pharmaceutical, chemical and biological agents

Examples

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examples

1. Reversible Lipidization of Particles

[0137]Chlorosilane lipids are used to “lipidize” the surface of a particle or liposome. Chemical modification by lipidization could improve oral bioavailability, minimize enzymatic degradation of the particle and / or its cargo, alter the circulation profiles of the nanoparticles, alter the biodistribution profile, alter the hydrophilic / hydrophobic character of the drug / cargo and / or change the charge of the drug until the particle or liposome contacts a pH range whereby the covalent Si linker is cleaved and the parent cargo / drug becomes available. The reversible nature of the attachment of the lipid allows for the loss of the lipid under controlled conditions. Once the particle has reached the target, e.g., the tumor, tissue, organ, cell of interest, etc., the lipid can be cleaved under slightly acidic conditions, that allows for better accessibility and easier release of the drug. In preferred embodiments, a drug as described elsewhere herein is...

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Abstract

Asymmetric bifunctional silyl (ABS) monomers comprising covalently linked pharmaceutical, chemical and biological agents are described. These agents can also be covalently bound via the silyl group to delivery vehicles for delivering the agents to desired targets or areas. Also described are delivery vehicles which contain ABS monomers comprising covalently linked agents and to vehicles that are covalently linked to the ABS monomers. The silyl modifications described herein can modify properties of the agents and vehicles, thereby providing desired solubility, stability, hydrophobicity and targeting.

Description

GOVERNMENT SUPPORT[0001]This invention was made with government support under Grants 1-DP1-OD006432-01, CA119343 and CA151652 awarded by the National Institutes of Health. The government has certain rights in the invention.FIELD OF THE INVENTION[0002]The subject matter herein is directed to asymmetric bifunctional silyl (ABS) monomers, such as silyl ether containing pharmaceutical, chemical and biological agents and delivery vehicles for these agents as well as ABS modified delivery vehicles themselves, such as liposomes and nanoparticles.BACKGROUND[0003]Drug delivery technology has been exploited extensively for the purpose of delivering agents to desired targets for many years. Drug delivery technologies involve liposomes and nano or microparticles. Hydrophobic or hydrophilic compounds can be entrapped in the hydrophobic domain or encapsulated in the aqueous compartment, respectively. Liposomes can be constructed of natural constituents so that the liposome membrane is in principa...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K47/48C07F7/08C07K19/00C07F7/18C07H23/00
CPCA61K47/48176A61K47/48215A61K47/4823A61K47/48238A61K47/48823A61K47/48869C07F7/083C07F7/184C07F7/1868C07H23/00C07K19/00A61K47/48023B82Y5/00A61K47/6913A61K47/58A61K47/60A61K47/61A61K47/62A61K47/6915A61K47/6925A61K47/6933C07F7/1804C12N15/113C12N2310/14C12N2310/3515C12N2320/32
Inventor DESIMONE, JOSEPH M.FINNISS, MATTHEWNAPIER, MARYPANDYA, ASHISHPARROTT, MATTHEW
Owner DESIMONE JOSEPH M
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