Lipid Nanoparticle Polyene Encapsulation to Reduce Antifungal Toxicity
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Solution Overview
Problem
Current treatments for Mucorales and Cryptococcus infections, such as mucormycosis and cryptococcosis, are ineffective and have high mortality rates due to resistance and toxicity issues with existing antifungal drugs like AmB, and there is a need for new formulations that enhance efficacy while reducing toxicity.
Innovation Solution
A composition comprising lipid nanoparticles with a polyene antifungal, such as AmB, dispersed in an aqueous phase and enveloped by a polyglycol ester of a hydroxy fatty acid, which forms a synergistic combination to increase antifungal efficacy and reduce toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If AmB is used as antifungal treatment, then antifungal efficacy is improved, but toxicity and nephrotoxicity increase
Solution Approach 1:
The patent introduces lipid nanoparticles as an intermediary carrier system that encapsulates AmB, allowing the drug to be delivered to fungal cells while reducing direct contact with host tissues. The nanoparticles act as a mediator between the antifungal agent and the target, improving efficacy while reducing toxicity through controlled release and targeted delivery mechanisms.
Solution Approach 2:
The patent modifies the physical and chemical parameters of AmB by incorporating it into lipid nanoparticle structures, changing its solubility, distribution, and release characteristics. This parameter transformation allows the drug to maintain antifungal activity while reducing nephrotoxicity through altered pharmacokinetic properties and reduced bioaccumulation in kidneys.
2Object-affected harmful factors
If liposomal formulations of AmB are used, then toxicity is reduced, but manufacturing complexity and cost increase
Solution Approach 1:
The patent segments the complex liposomal formulation process into simplified nanoparticle systems with standardized manufacturing protocols. By dividing the formulation into discrete, controllable steps and using modular nanoparticle designs, the manufacturing complexity is reduced while maintaining the toxicity-reduction benefits of liposomal delivery.
3Ease of manufacture
If AmB deoxycholate is used in developing countries, then cost is reduced, but antifungal efficacy remains low
Solution Approach 1:
The patent creates composite nanoparticle systems that combine AmB with lipid components to form enhanced antifungal formulations. These composite structures improve the efficacy of cost-effective AmB preparations, making them suitable for use in developing countries while maintaining affordability through simplified manufacturing processes.
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 combination significantly enhances the antifungal activity against Mucorales, Aspergillus, and Cryptococcus, reducing toxicity and improving treatment outcomes, with potential for nebulized administration to overcome fungal resistance and increase pulmonary residence time.
Implementation Method 1
lipid nanoparticles which are dispersed in the aqueous phase, said lipid nanoparticles comprising an oily internal phase and an envelope, the envelope comprising a polyglycol ester of a hydroxy fatty acid
Implementation Method 2
the polyene antifungal being dispersed in the aqueous phase and/or being part of the lipid nanoparticles
Data Source
AI summary
The present invention relates to a composition comprising an aqueous phase, a polyene antifungal and lipid nanoparticles which are dispersed in the aqueous phase, said lipid nanoparticles comprising an oily internal phase and an envelope, the envelope comprising a polyglycol ester of a hydroxy fatty acid, the polyene antifungal being dispersed in the aqueous phase and/or being part of the lipid nanoparticles. It further relates to lipid nanoparticles comprising an antifungal polyene, an oily internal phase and an envelope, the envelope comprising a polyglycol ester of a hydroxy fatty acid and the polyene antifungal being part of the lipid nanoparticles, and preparation method thereof. It also relates to the composition or lipid nanoparticles of the invention for use in the prevention or treatment of an infection caused by a fungus, preferably a fungus of the Mucorales order.