Stable TLR Agonist Formulations with Cyclodextrin
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Solution Overview
Problem
Current pharmaceutical formulations for toll-like receptor (TLR) agonists lack stability and effective delivery methods for treating cancer and infectious diseases, particularly for solid tumors, lymphomas, and viral infections, with limited options for combination therapies.
Innovation Solution
Development of stable benzo[b]azepine TLR agonist formulations, specifically for TLR7 or TLR8, incorporating sulfobutylether β-cyclodextrin as a solubilizing agent, suitable for subcutaneous, intramuscular, or transdermal administration, and combination with chemotherapeutic agents, cytokines, or vaccines for enhanced therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TLR agonists are formulated at high concentrations for effective cancer and infectious disease treatment, then therapeutic efficacy is improved, but formulation stability deteriorates
Solution Approach 1:
Sulfobutylether β-cyclodextrin serves as a mediating substance that forms inclusion complexes with the TLR agonist, enabling high concentrations of the active ingredient to be stabilized in aqueous formulation. The cyclodextrin cavity encapsulates the hydrophobic TLR agonist molecules, preventing aggregation and degradation while maintaining high drug concentration for effective therapy.
2Reliability
If TLR agonists are formulated for intravenous administration to treat solid tumors and lymphomas, then treatment effectiveness is improved, but solubility requirements become more stringent
Solution Approach 1:
The formulation utilizes sulfobutylether β-cyclodextrin to fundamentally change the solubility parameters of the TLR agonist. The cyclodextrin inclusion complexation transforms the poorly water-soluble TLR agonist into a highly soluble aqueous formulation, enabling intravenous administration at concentrations sufficient to treat solid tumors and lymphomas effectively.
3Reliability
If combination therapies with chemotherapeutic agents and cytokines are implemented, then therapeutic outcomes are improved, but formulation complexity increases
Solution Approach 1:
The sulfobutylether β-cyclodextrin-based formulation platform provides multi-functionality by serving as a universal solubilizing and stabilizing system for TLR agonists that can be combined with various chemotherapeutic agents and cytokines. This single formulation approach handles multiple therapeutic combinations without requiring separate complex formulation development for each combination.
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 provide stable and soluble benzo[b]azepine TLR agonists, enhancing their biological activity and solubility, allowing for effective treatment of cancers such as ovarian, breast, and lymphoma, as well as viral infections like hepatitis C, with improved stability and compatibility for combination therapies.
Implementation Method 1
the formulation comprises about 1-30%, 5-15%, or 5-10% weight/volume (w/v) of a sulfobutylether β-cyclodextrin
Data Source
AI summary
The present invention is directed generally to stable formulations of a TLR agonist preferably a TLR7 or a TLR8 agonist, for use in the treatment of cancer, preferably solid tumors and lymphomas. Specifically, the present invention is directed to stable formulations of up to 50 mg/ml of a TLR agonist which comprise a cyclodextrin.