Lipid Nanoparticle Lyophile Formulation for Stable Storage
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Solution Overview
Problem
Existing methods for storing lipid nanoparticles encapsulating nucleic acid agents are limited by instability and degradation, making long-term storage and reconstitution challenging.
Innovation Solution
A composition comprising an aqueous suspension of lipid nanoparticles, a dextrin compound, and a saccharide sugar compound, which can be lyophilized to form a stable solid form and reconstituted to maintain the nanoparticles' transfection activity and size.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If lipid nanoparticles are stored at 25°C or 4°C, then they can be stored for short periods, but they degrade quickly and lose stability
Solution Approach 1:
The patent changes the physical state parameter of the nanoparticle composition from liquid to solid through lyophilization. By converting the composition to a solid lyophile form, the storage stability is dramatically improved, allowing long-term storage at 4°C without degradation, thereby resolving the contradiction between storage duration and compositional stability.
2Duration of action of stationary object
If lyophilization is performed on lipid nanoparticles, then long-term storage is enabled, but the nanoparticles and nucleic acid agents are destroyed
Solution Approach 1:
The patent applies beforehand cushioning by incorporating stabilizing excipients and protective agents into the nanoparticle composition prior to lyophilization. These additives cushion and protect the lipid nanoparticles and encapsulated nucleic acid agents during the lyophilization process, preventing their destruction while enabling long-term storage in solid form.
Solution Approach 2:
The patent creates a composite material system by combining lipid nanoparticles with stabilizing excipients and protective agents. This composite formulation maintains nanoparticle integrity during lyophilization by providing structural support and protective environment, allowing the nanoparticles to survive the drying process while achieving long-term storage stability.
3Stability of the object's composition
If chemical protective groups are attached to lipid nanoparticles or nucleic acid agents, then stability during lyophilization is improved, but the process becomes more complex and requires additional chemical modifications
Solution Approach 1:
The patent employs simple, readily available stabilizing excipients and protective agents that can be easily incorporated into the nanoparticle formulation without requiring complex chemical synthesis or modification. These straightforward additives provide the necessary protection during lyophilization while keeping the formulation process simple and accessible.
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 method allows for the stable storage of lipid nanoparticles with encapsulated nucleic acid agents, maintaining their transfection activity and particle size upon reconstitution, even after long-term storage.
Implementation Method 1
The composition can be lyophilized to form a stable solid form
Implementation Method 2
an aqueous suspension of the lipid nanoparticles in a pharmaceutically acceptable solution
Data Source
AI summary
Compositions for making a solid lyophile of one or more nucleic acid active agents, which can be reconstituted as a drug product. The composition can include an aqueous suspension of lipid nanoparticles in a pharmaceutically acceptable solution, wherein the lipid nanoparticles encapsulate one or more nucleic acid active agents, a dextrin compound, and a saccharide compound. The nucleic acid active agents can be RNAi molecules capable of mediating RNA interference, as well as other RNAs and oligonucleotides.