Albumin Complexes for Stable Drug Delivery

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Solution Overview

Problem

Current methods for delivering small organic and inorganic molecules, such as drugs and imaging agents, face challenges including instability, lack of specificity, immunogenicity, and toxicity due to inefficient delivery mechanisms, which hinder their therapeutic and diagnostic potential.

Innovation Solution

Recombinant animal albumin proteins with inserted ligand-binding domains are used to form complexes with fatty acid-conjugated molecules, enhancing delivery by binding to specific ligands on cells or tissues, thereby improving targeting and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If small organic molecules and inorganic drugs are delivered using conventional methods, then delivery is achieved, but stability and specificity are poor leading to toxicity and immunogenicity

Engineering Contradiction:
Improvedelivery stabilityVSAvoidtoxicity and immunogenicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses fatty acid-conjugated molecules as intermediaries to bridge the small molecule drugs and albumin proteins. The fatty acid conjugation creates a specific binding interface that allows stable complex formation with albumin, thereby improving delivery reliability while reducing the harmful effects of free small molecules through controlled complexation

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If conventional delivery mechanisms are used for small molecules, then delivery occurs, but specificity to desired cells and tissues is lacking

Engineering Contradiction:
Improvedelivery efficiencyVSAvoidtargeting specificity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent introduces ligand-binding domains at specific locations on the albumin protein structure. These localized binding sites provide specific recognition for target cells and tissues, thereby improving targeting precision without compromising the overall delivery efficiency of the complex

Inventive Principle:
Principle #3Local quality

3Measurement precision

If chemical modification of albumin is performed to enhance targeting, then targeting ability improves, but immunogenicity and aggregation increase

Engineering Contradiction:
Improvetargeting abilityVSAvoidimmunogenicity and aggregation
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent segments the targeting function from the albumin core by using separate ligand-binding domains that associate with albumin through fatty acid conjugation. This modular approach allows targeting ability to be enhanced while maintaining the native structure and low immunogenicity of the albumin core, preventing aggregation

Inventive Principle:
Principle #1Segmentation

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach enhances the delivery and stability of therapeutic and diagnostic molecules, reducing toxicity and immunogenicity, and allows for more specific targeting of cells and tissues, improving their therapeutic and diagnostic efficacy.

Implementation Method 1

Human serum albumin (HSA) is known to bind an extraordinarily wide range of metabolites and drugs

Methodology Applied
Scientific EffectNon-covalent binding: Absorption (physical)

Implementation Method 2

The ligand bound by the domain can be any of a wide variety of ligands including, for example, ligands that occur on the surface of a cell of an animal, ligands that occur in a tissue of an animal

Methodology Applied
Scientific EffectLigand binding: Adsorption

Data Source

PatentUS9309303B2Complexation of fatty acid-conjugated molecules with albumin
Publication Date: 2016.04.12 UNIV OF THE SCI & PHILADELPHIA
  • US9309303B2 patent drawing
  • US9309303B2 patent drawing
  • US9309303B2 patent drawing

AI summary

The present disclosure relates generally to novel methods and compositions for using engineered reprogramming factor(s) for the creation of induced pluripotent stem cells (iPSCs) through a kinetically controlled process. Specifically, this disclosure relates to establishing combinations of reprogramming factors, including fusions between conventional reprogramming factors with transactivation domains, optimized for reprogramming various types of cells. More specifically, the exemplary methods disclosed herein can be used for creating induced pluripotent stem cells from various mammalian cell types, including human fibroblasts. Exemplary methods of feeder-free derivation of human induced pluripotent stem cells using synthetic messenger RNA are also disclosed.