Biphasic Vesicle Formulation for Intracellular Antimicrobial Delivery
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Solution Overview
Problem
Current antimicrobial treatments for pathogens like Burkholderia pseudomallei, Francisella tularensis, and VEEV face challenges due to antimicrobial resistance, inefficacy in intracellular environments, and side effects from multiple antibiotic regimens, with a lack of effective vaccines and optimized delivery systems.
Innovation Solution
A method for preparing pharmaceutical-vesicle formulations using Non-Ionic Surfactant Vesicles (NISVs) that entrap antibiotics like levofloxacin and doxycycline, modified with glucosamine and transferrin to enhance delivery across barriers and target specific tissues, using automated equipment like NanoAssemblr®, resulting in biphasic formulations for improved efficacy and reduced side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If combination therapy with multiple antibiotics is used to improve efficacy against B. pseudomallei, then antimicrobial effectiveness is improved, but side effects and treatment complexity increase
Solution Approach 1:
The patent combines multiple antibiotics (levofloxacin and doxycycline) into a single vesicular formulation, allowing simultaneous delivery of both agents. This merging approach maintains the synergistic antimicrobial effectiveness of combination therapy while reducing the number of separate administrations required, thereby decreasing treatment complexity and potential side effects associated with multiple separate treatments.
Solution Approach 2:
The vesicular formulation acts as an intermediary delivery system that encapsulates multiple antibiotics. This intermediary structure protects the antibiotics during delivery, controls their release, and facilitates their co-administration in a single therapeutic agent, thereby maintaining efficacy while reducing the harmful effects of multiple separate administrations.
2Ease of operation
If conventional antibiotic administration is used, then treatment simplicity is maintained, but efficacy against intracellular pathogens is insufficient
Solution Approach 1:
The patent modifies the physical and chemical parameters of antibiotic delivery by encapsulating them in vesicles. This changes the delivery mechanism from conventional free antibiotic administration to vesicle-mediated delivery, which enhances penetration into intracellular environments while maintaining the simplicity of oral or parenteral administration. The vesicular structure allows the antibiotics to reach intracellular pathogens effectively without complicating the treatment regimen.
3Ease of operation
If single antibiotic dosing is used to maintain treatment simplicity, then ease of administration is improved, but antimicrobial effectiveness against B. pseudomallei is insufficient
Solution Approach 1:
The patent merges multiple antibiotics into a single vesicular formulation that can be administered as one dose. This combining approach allows the delivery of multiple antimicrobial agents simultaneously, maintaining the ease of single-dose administration while achieving the synergistic effectiveness that would otherwise require multiple separate antibiotics.
Solution Approach 2:
The vesicular formulation serves multiple functions within a single therapeutic agent: it delivers multiple antibiotics, protects them during transit, facilitates cellular uptake, and enables intracellular delivery. This multi-functionality allows single-dose administration to achieve effectiveness comparable to or exceeding that of multiple separate antibiotic treatments.
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 vesicle formulations enhance cellular uptake, target pathogens effectively, reduce side effects, and maintain antimicrobial activity, demonstrating increased survival rates and reduced weight loss in animal models.
Implementation Method 1
heating vesicle components comprising a surfactant, a hydrophobic substance and an amphiphile
Implementation Method 2
processing the formulation mixture to entrap the pharmaceutical agent and carrier in a vesicle
Implementation Method 3
the vesicles are modified with i) glucosamine and/or ii) transferrin... recognised by an in vivo receptor-mediated transport mechanism
Data Source
Figure 1
Figure 2A~2B
Figure 3
AI summary
The invention relates to methods for the preparation of a pharmaceutical -vesicle formulation comprising steps of: preparing and processing vesicle components and a pharmaceutical agent to entrap the pharmaceutical agent in the vesicle and form a pharmaceutical-vesicle formulation, wherein the pharmaceutical-vesicle formulation is reconstituted in a known quantity of the pharmaceutical agent dissolved in a pharmaceutically-acceptable carrier to provide a biphasic pharmaceutical-vesicle formulation. The invention also relates to the associated pharmaceutical-vesicle formulations, pharmaceutical kits and uses as a medicament, in particular for the prevention or treatment of infection by bacteria such as Burkholderia pseudomallei and Francisella tularensis, and viruses such as Venezuelan Equine Encephalitis Virus (VEEV).