Stable Exosome Formulations via Lyophilization
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Solution Overview
Problem
Current exosome formulations for clinical use lack stability, particularly in maintaining the levels of miR-210 and miR-146A, which are crucial for their therapeutic benefits in cardiac tissue repair, and face challenges in long-term storage and bioactivity retention.
Innovation Solution
Development of stable lyophilized and liquid exosome formulations generated from cardiosphere-derived cells using ultrafiltration and diafiltration, which maintain at least 90% of miR-210 and miR-146A levels and in vitro/in vivo biological activity for extended periods, including after lyophilization and rehydration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If exosomes are stored in liquid form at refrigerated or frozen temperatures, then their storage duration is extended, but their stability and bioactivity are compromised over time
Solution Approach 1:
The patent applies freeze-drying (lyophilization) technology to transform exosomes from liquid state to solid dried state, and then rehydrates them back to liquid form for storage. This phase transition process removes water completely during freezing and drying, then restores it controllably, achieving both extended storage duration and maintained bioactivity without requiring continuous refrigeration or freezing.
Solution Approach 2:
The invention changes the physical state parameters of exosomes from liquid to dried powder form through controlled freeze-drying processes. By adjusting parameters such as freezing temperature, drying time, and rehydration conditions, the patent achieves stable storage at ambient temperatures while preserving miR-210 and miR-146A levels and biological activity.
2Stability of the object's composition
If exosomes are lyophilized and rehydrated, then storage stability is improved, but manufacturing complexity increases
Solution Approach 1:
The patent performs preliminary freeze-drying of exosome formulations before final storage preparation. By pre-freezing and lyophilizing the exosomes in controlled manufacturing conditions, the formulation is stabilized in advance, allowing simple storage and transport without complex temperature control systems during distribution and use.
3Quantity of substance
If conventional isolation methods are used, then exosome yield is achieved, but miR-210 and miR-146A levels deteriorate during storage
Solution Approach 1:
The patent uses freeze-drying to remove water from exosome formulations, transforming them from liquid to solid state. This phase transition prevents degradation of miR-210 and miR-146A by eliminating the aqueous environment that facilitates enzymatic degradation and chemical breakdown, thereby preserving these critical molecules during long-term storage.
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
The stable formulations retain high levels of miR-210 and miR-146A, along with bioactivity, even after storage and lyophilization, demonstrating improved stability and effectiveness in cardioprotective and angiogenic functions.
Implementation Method 1
stable liquid cardiosphere-derived cell (CDC) exosome formulation suitable for administration to a human, wherein the exosome formulation is generated from CDCs by ultrafiltration and diafiltration
Implementation Method 2
stable liquid cardiosphere-derived cell (CDC) exosome formulation suitable for administration to a human, wherein the exosome formulation is generated from CDCs by ultrafiltration and diafiltration
Implementation Method 3
stable lyophilized exosome formulation suitable for administration to a human comprising at least 10 6 particles/mL or 10 8 particles/mL
Data Source
Figure 1A~1B
Figure 1C~1D
Figure 2
AI summary
The invention encompasses methods for generating stable exosome formulations and encompasses stable exosome formulations. The exosome formulations encompass stable liquid exosome formulations and stable lyophilized exosome formulations. In some embodiments, the exosome formulations can be generated by ultrafiltration and diafiltration. The exosome formulations can be suitable for administration to a human.