Aqueous Silk Microsphere Preparation via Sonication
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Solution Overview
Problem
Existing methods for producing microspheres for drug delivery often require organic solvents and high temperatures, which can degrade or inactivate therapeutic agents, making them unsuitable for temperature-sensitive drugs and limiting the bioactivity of encapsulated agents.
Innovation Solution
A novel, all-aqueous method to produce beta-sheet crystalline, porous silk microspheres using sonication to induce beta-sheet structure formation in silk fibroin solutions, avoiding the need for organic solvents and high temperatures, allowing for the encapsulation of therapeutic agents like bevacizumab or memantine while maintaining their bioactivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing methods for generating microspheres are used, then microspheres can be produced, but organic solvents and high temperatures cause degradation or inactivation of therapeutic agents
Solution Approach 1:
The patent changes the preparation parameters from conventional organic solvents and high temperatures to an all-aqueous system with controlled sonication and pH adjustment. Specifically, the patent uses aqueous calcium chloride solution at controlled pH (6.5-7.5) with sonication treatment to induce beta-sheet formation and microsphere precipitation, avoiding the harmful effects of organic solvents and excessive heat on therapeutic agents
Solution Approach 2:
The patent replaces thermal and chemical processing mechanisms with mechanical sonication energy. Ultrasound waves are used to induce beta-sheet conformational changes in silk fibroin and facilitate microsphere formation without requiring high temperatures or organic solvents, thereby preserving therapeutic agent bioactivity
2Reliability
If all-aqueous method with sonication is used, then therapeutic agent bioactivity is maintained, but beta-sheet structure formation and microsphere insolubility must be achieved without organic solvents
Solution Approach 1:
The patent achieves beta-sheet structure formation and insolubility by precisely controlling aqueous solution parameters including pH (6.5-7.5), ionic strength (calcium chloride concentration), and sonication conditions. These parameter adjustments enable the silk fibroin to undergo conformational change and precipitate as insoluble microspheres in purely aqueous conditions
Solution Approach 2:
The patent uses calcium ions and controlled pH conditions as intermediaries to facilitate beta-sheet formation and microsphere precipitation. The calcium chloride solution acts as a mediating environment that induces silk fibroin conformational changes and promotes microsphere formation without requiring organic solvents
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
This method enables the production of silk microspheres that effectively encapsulate and deliver therapeutic agents with maintained bioactivity, suitable for sustained release applications without the need for harsh chemicals or high temperatures, enhancing the yield and bioavailability of the encapsulated drugs.
Implementation Method 1
a silk fibroin solution can be sonicated (e.g., at a frequency of about 10 kHz or higher) to induce formation of beta-sheet structures of fibroin
Implementation Method 2
induce formation of beta-sheet structures of fibroin, and simultaneously form a spray of silk microspheres rich in beta-sheet crystalline structure
Implementation Method 3
the silk microsphere can be further freeze-dried to induce a higher degree of micro/nanoporosity
Data Source
AI summary
Provided herein relates to methods and compositions for preparing a silk microsphere and the resulting silk microsphere. In some embodiments, the methods and compositions described herein are all aqueous, which can be used for encapsulating an active agent in a silk microsphere, while maintaining activity of the active agent during processing. In some embodiments, the resulting silk microsphere can be used for sustained delivery of an active agent encapsulated therein.