Cochleate Formation via Solvent-Assisted Precipitation
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Solution Overview
Problem
Current methods for forming cochleates are time-consuming and costly, and they often result in unstable particle sizes and poor absorption of cargo moieties, particularly for poorly absorbed drugs like aminoglycopeptides and aminoglycosides, leading to toxic side effects and ineffective delivery.
Innovation Solution
A novel method involving the introduction of a cargo moiety to a liposome in the presence of a solvent, such as dimethylsulfoxide, followed by precipitation to form cochleates, which includes the use of aggregation inhibitors to stabilize particle size and incorporate protonized cargo moieties with divalent cations, enabling efficient and stable delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to form cochleates through solvent removal and hydration, then cochleate structures can be formed, but the process is time-consuming and increases manufacturing cost
Solution Approach 1:
The invention changes the fundamental parameter of cochleate formation from a multi-step process involving solvent removal and hydration to a direct precipitation process using divalent cations. This parameter change eliminates intermediate steps, reducing manufacturing time while maintaining reliable cochleate structure formation through the direct interaction of negatively charged lipids with divalent cations to form stable precipitates
Solution Approach 2:
The invention extracts and eliminates the time-consuming steps of solvent removal and hydration from the cochleate formation process. By taking out these intermediate steps and replacing them with direct precipitation using divalent cations, the method achieves faster manufacturing while preserving the essential cochleate structure formation
2Reliability
If conventional cochleate preparation methods are used, then cochleates can be formed, but particle size and particle size distribution become highly variable and unstable
Solution Approach 1:
The invention introduces feedback control through the use of divalent cations that directly interact with negatively charged lipids to form precipitates. This mechanism provides inherent control over particle size and distribution by regulating the precipitation process, ensuring stable and consistent cochleate formation without the variability observed in conventional methods
Solution Approach 2:
The invention changes the formation mechanism parameter from solvent-based assembly to cation-driven precipitation. This parameter change enables better control over particle size and distribution stability, as the direct interaction between divalent cations and negatively charged lipids creates more consistent and stable cochleate structures
3Reliability
If large amounts of poorly absorbed drugs are administered to achieve effective delivery, then therapeutic effect can be achieved, but toxic side effects accumulate in the GI tract and bloodstream
Solution Approach 1:
The invention introduces cochleates as an intermediary delivery vehicle that mediates between the poorly absorbed drug and the body's absorption mechanisms. The cochleate structure facilitates controlled delivery and absorption of the cargo moiety, achieving therapeutic effects while preventing toxic accumulation by regulating the release and absorption rate of the drug
Solution Approach 2:
The invention uses the flexible liposomal shell of the cochleate to encapsulate and protect the cargo moiety. This flexible shell structure enables controlled interaction with biological membranes, facilitating absorption while preventing premature release and toxic accumulation in the GI tract and bloodstream
4Reliability
If poorly absorbed drugs are administered to treat bacterial infections, then therapeutic coverage can be achieved, but poor delivery to cells harboring bacteria occurs
Solution Approach 1:
The invention introduces cochleates as an intermediary delivery system that bridges the gap between poorly absorbed drugs and cellular targets. The cochleate structure facilitates precise delivery to cells harboring bacteria by enabling membrane interaction and cellular uptake, achieving both therapeutic coverage and delivery precision simultaneously
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 method allows for the efficient and stable formation of cochleates with controlled particle sizes, enhancing the absorption and delivery of cargo moieties, reducing toxicity and improving the effectiveness of poorly absorbed drugs.
Implementation Method 1
introducing a cargo moiety to a liposome in the presence of a solvent such that the cargo moiety associates with the liposome
Implementation Method 2
precipitating the liposome to form a cargo moiety-cochleate
Implementation Method 3
cochleates including a protonized cargo moiety, divalent cation and negatively charged lipid
Data Source
AI summary
Disclosed are novel methods for making cochleates and cochleate compositions that include introducing a cargo moiety to a liposome in the presence of a solvent. Also disclosed are cochleates and cochleate compositions that include an aggregation inhibitor, and optionally, a cargo moiety. Additionally, anhydrous cochleates that include a protonized cargo moiety, a divalent metal cation and a negatively charge lipid are disclosed. Methods of using the cochleate compositions of the invention, including methods of administration, are also disclosed.