TLR2 Agonist Formulations with Cyclodextrin for Stability
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Solution Overview
Problem
Existing TLR2 agonist compositions suffer from stability issues under ambient conditions, limiting their effectiveness and shelf-life, and current treatments for respiratory diseases like asthma and COPD exacerbations are inadequate.
Innovation Solution
Formulating TLR2 agonists with cyclodextrin and solubilizing moieties such as polyethylene glycol (PEG) or sugar compounds like mannitol, erythritol, xylitol, and sorbitol to enhance stability and bioavailability, and administering them via nasal or inhalation routes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TLR2 agonists are conjugated with solubilizing moieties to enhance solubility and bioavailability, then bioavailability is improved, but stability is reduced
Solution Approach 1:
Cyclodextrins are used as intermediary molecules that form inclusion complexes with TLR2 agonists. The cyclodextrin cavity encapsulates the hydrophobic agonist portion while the hydrophilic exterior maintains solubility, thereby simultaneously improving both stability and bioavailability without direct conjugation of the agonist to solubilizing moieties
Solution Approach 2:
The formulation creates a composite system combining cyclodextrin host molecules with TLR2 agonist guest molecules. This composite approach allows the system to exhibit both the stability of the cyclodextrin-agonist complex and the enhanced solubility provided by the cyclodextrin structure, avoiding the instability issues of direct conjugation
2Ease of manufacture
If conventional excipients are used in TLR2 agonist formulations, then formulation is simplified, but stability is compromised
Solution Approach 1:
The invention changes the fundamental formulation parameter from using conventional excipients to using cyclodextrin-based complexes. This parameter change fundamentally alters the formulation chemistry to achieve stability while maintaining practical manufacturability through well-established cyclodextrin formulation techniques
3Reliability
If vaccines are administered to prevent respiratory infections, then protection is provided, but there is a lag phase before antibodies are formed
Solution Approach 1:
The TLR2 agonist formulation is administered as a preliminary action to prime the innate immune system before viral exposure or in conjunction with vaccination. By activating TLR2 receptors, the formulation prepares immune cells (macrophages, dendritic cells) to respond more rapidly and effectively, reducing the protective lag phase
Solution Approach 2:
The formulation provides continuous immune stimulation through TLR2 activation, maintaining immune system readiness rather than relying solely on the transient antibody response from vaccination. This continuous action ensures protection during the period before vaccine-induced antibodies become effective
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 formulations maintain stability and improve bioavailability, effectively stimulating innate immune responses to treat and prevent respiratory infections and reduce inflammation, providing a stable and effective treatment for respiratory diseases.
Implementation Method 1
The compositions comprise a cyclodextrin and a compound comprising a TLR2 agonist moiety conjugated with a solubilising moiety
Implementation Method 2
a sugar compound selected from mannitol, erythritol, xylitol, sorbitol, myo-inositol or a combination thereof
Data Source
AI summary
This invention relates to pharmaceutical compositions comprising a compound comprising a TLR2 agonist moiety conjugated with a solubilising moiety and an excipient that stabilises the compound under accelerated aging conditions. Also disclosed is the preparation of powdered forms of the compositions and methods for their use.