Biodegradable pH-Sensitive Polymer Micelles for Repeat Drug Delivery
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Solution Overview
Problem
Current pH-sensitive polymers with non-degradable backbones pose challenges for repeated use due to accumulation in the body, limiting their safety in applications requiring multiple injections, such as drug or gene delivery.
Innovation Solution
Development of biodegradable polymers with a hydrophobic and hydrophilic segment that undergoes pH-sensitive degradation, forming micelles and disassociating at specific pH levels, allowing for targeted drug delivery and clearance from the body.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If non-degradable PMMA polymer backbones are used in UPS copolymers, then sharp pH response and precision in biological applications are improved, but material accumulation in the body occurs and safety is compromised for repeated use
Solution Approach 1:
The polymer is divided into distinct functional segments: a degradable backbone (polyurea or polycarbonate) that provides biodegradability and a side chain with ionizable groups that provides pH sensitivity. This segmentation allows each component to fulfill its specific function without compromising the other, resolving the contradiction between precision and safety.
Solution Approach 2:
The invention creates a composite polymer structure combining degradable backbone units (polyurea or polycarbonate) with ionizable side chains (tertiary amines). This composite approach integrates the benefits of both components: the degradable backbone ensures safety for repeated use while the ionizable side chains maintain sharp pH response for precision applications.
2Reliability
If degradable polymer backbones are used, then safety and clearance from the body are improved, but pH response precision may be compromised
Solution Approach 1:
By separating the degradable backbone function from the pH-sensing function in different polymer segments, the invention ensures that the degradable backbone provides safety and clearance while the ionizable side chains in the side chain maintain sharp pH response, thus resolving the contradiction.
Solution Approach 2:
The ionizable groups are localized in the side chain region of the polymer, while the degradable backbone provides the structural framework. This local quality differentiation ensures that pH response precision is maintained in the side chain while the backbone provides safety and biodegradability.
3Productivity
If repeated injections are administered for drug or gene delivery, then therapeutic effectiveness is improved, but material accumulation and toxicity increase
Solution Approach 1:
The degradable backbone is designed to be metabolically cleared from the body after performing its function. The polymer breaks down into non-toxic fragments that are excreted, allowing repeated administrations without accumulation or toxicity, thus enabling continuous therapeutic delivery.
Solution Approach 2:
The polymer is designed as a temporary, biodegradable carrier that performs its therapeutic delivery function and then is cleared from the body. This disposable-like approach allows multiple uses without long-term accumulation, improving safety for repeated injections.
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 biodegradable polymers provide precise pH-responsive delivery of therapeutic agents, enhancing safety by minimizing material accumulation and enabling repeated use without toxicity concerns.
Implementation Method 1
biodegradable polymers with a hydrophobic and hydrophilic segment that undergoes pH-sensitive degradation
Implementation Method 2
forming micelles and disassociating at specific pH levels
Implementation Method 3
biodegradable polymers with a hydrophobic and hydrophilic segment
Implementation Method 4
biodegradable polymers with a hydrophobic and hydrophilic segment
Data Source
AI summary
The present disclosure relates to degradable polymers which contain a hydrophobic and hydrophilic segment which is sensitive to pH. In some aspects, the polymers form a micelle which is sensitive to pH and have backbones which are capable of undergoing degradation in vivo. In some aspects, the disclosure also provides methods of using these degradable polymers for the delivery of a drug.