Cationic lipid compositions for tissue-specific delivery

a lipid composition and tissue technology, applied in the direction of hydrolases, drug compositions, organic active ingredients, etc., can solve the problem of design lipid nanoparticles capable of targeting specific organs, tissues, or cell types without the use of canonical biomolecular targeting techniques, and achieve the effect of improving the stability and stability of the lipid nanoparticl

Inactive Publication Date: 2019-02-28
LIFE TECH CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0021]In another aspect is provided a method of delivering a bioactive agent to lung tissue in a subject, the method including: (i) admixing an bioactive agent with a composition as described herein including embodiments thereof, thereby forming a bioactive agent-lipid complex; (ii) systemically administering an effective amount of the bioactive agent-lipid complex to a subject, thereby delivering the bioactive agent-lipid complex to a lung tissue in a subject.
[0022]In another aspect is provided a method of expressing a protein in lung tissue in a subject, the method including: (i) admixing a mRNA with a composition as described herein including embodiments thereof, thereby forming a mRNA-lipid complex; (ii) administering an effective amount of the mRNA-lipid complex to a subject; and (iii) allowing the mRNA of the mRNA-lipid complex to express in lung tissue of the subject, thereby expressing a protein in lung tissue in a subject.
[0023]In an aspect is provided a method of treating a pulmonary disease in a subject in need thereof, the method including administering to a subject a therapeutically effective amount of a bioactive agent and a composition as described herein including embodiments thereof, thereby treating a pulmonary disease in the subject.

Problems solved by technology

Designing lipid nanoparticles capable of targeting specific organs, tissues, or cell types without the use of canonical biomolecular targeting techniques has been a significant challenge.

Method used

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  • Cationic lipid compositions for tissue-specific delivery
  • Cationic lipid compositions for tissue-specific delivery
  • Cationic lipid compositions for tissue-specific delivery

Examples

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example 1

id Nanoparticles for In Vivo Lung Targeted mRNA and siRNA Delivery

[0218]The rapidly expanding utilization of nucleic acids as a therapeutic tool has presented the field with the task of optimizing and innovating delivery methods. Lipid nanoparticles are a common delivery vehicle due to their ability to facilitate cellular uptake while protecting the payload from extracellular enzyme degradation. Organ and tissue specific delivery of sensitive payloads such as mRNA is of great importance in tailoring therapeutic functionality. This is commonly achieved using biomolecular targeting via ligand or receptor expression on the surface of the nanoparticle. However, manipulation of the inherent properties of nanoparticles affords the opportunity to tailor the location of delivery to a specific organ of interest.

[0219]Applicants have developed novel lipid nanoparticles that are specifically optimized for use in vivo, and engineered to inherently target and deliver nucleic acid payloads (mRNA ...

example 2

nt of Novel Lipid Nanoparticles for In Vivo Lung Targeted mRNA Delivery

[0220]Abstract.

[0221]The rapidly expanding utilization of mRNA as a therapeutic tool has presented the field with the task of optimizing and innovating delivery methods. As the applications for RNA based therapeutics continues to rise, a parallel emerging need to improve upon and develop novel technology has come to the forefront. Lipid nanoparticles area common delivery vehicle for mRNA due to their ability to facilitate cellular uptake while protecting the mRNA from extracellular enzyme degradation. Organ and tissue specific delivery of mRNA is of great importance in tailoring therapeutic functionality. This is commonly achieved using biomolecular targeting via ligand or receptor expression on the surface of the nanoparticle.

[0222]Applicants have developed novel lipid nanoparticles that are specifically optimized for use in vivo, and engineered to inherently target and deliver mRNA to murine lungs and spleen wi...

example 3

on and Complexation

[0237]Formulation Preparation.

[0238]Prepare stock solutions of the individual lipid components in 100% Ethanol (EtOH) at appropriate concentrations based on individual lipid solubility. Heat to 50° C. to dissolve lipids completely in the EtOH. In a glass vial, combine all 5 lipid components using a pipette in volumes calculated according to Molar ratios listed in Table 1. Dilute the combined lipids using 200 mM Sodium Acetate at a dilution ratio of 1:4 by volume. Seal lid with paraffin. Store at 4° C.

[0239]Complexation Preparation.

[0240]Concentration of lipid is delivered at a 3 mg / kg concentration. Concentration of mRNA is a 10:1 dilution, so 0.3 mg / mL total mRNA are administered. Label 2 screw-cap plastic sample tubes as ‘lipid’ and ‘mRNA’. Transfer 100 μL of prepared lipid formulation to tube labeled ‘lipid’. Calculate amount of mRNA needed for 200 μL total volume of complex. (0.6 mg / mL) Since lipid formulation is at a 25% EtOH solution following the 1:4 diluti...

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Abstract

Provided herein are, inter alia, compositions and methods useful for the in vivo delivery of bioactive agents (e.g., therapeutic or diagnostic agents). The compositions provided herein include cationic lipids, helper lipids and a biostability enhancing agent, which together form a lipid aggregate with the bioactive agent and allow for the systemic delivery of the bioactive agent to, for example, lung tissue without the requirement for biomolecular targeting.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority to U.S. Provisional Application No. 62 / 552,783, filed Aug. 31, 2017, which disclosure is herein incorporated by reference in its entirety.BACKGROUND OF THE INVENTION[0002]Delivery of payloads such as therapeutic nucleic acids to specific tissues has traditionally been achieved using biomolecular targeting via ligand or receptor expression on the surface of lipid nanoparticles which serve as a delivery vehicle. Designing lipid nanoparticles capable of targeting specific organs, tissues, or cell types without the use of canonical biomolecular targeting techniques has been a significant challenge. Manipulation of the inherent properties of lipid nanoparticles affords a means of achieving organ, tissue, and cell-type specific targeting. Provided herein are compositions and methods which cure this and other needs in the art.BRIEF SUMMARY OF THE INVENTION[0003]In an aspect is provided a compositio...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K47/69A61K9/127C12N9/22A61K31/7105A61K47/54A61P11/00
CPCA61K47/6917A61K9/1272C12N9/22A61K31/7105A61K47/549A61P11/00A61K9/0019A61K31/713C12N15/88A61K47/541
Inventor MISHRA, SHIKHADE MOLLERAT DU JEU, XAVIER
Owner LIFE TECH CORP
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