pH-Sensitive Nanoparticle Formulation for Oral Protein Delivery
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Solution Overview
Problem
Existing methods for oral delivery of proteins and peptides face challenges such as degradation in the stomach, chemical instability, and the need for parenteral administration, with a lack of suitable formulations for non-injectable forms like oral dosage forms.
Innovation Solution
Development of pH-sensitive nanoparticles with a mean particle size of 50 nm or less, composed of a pH-sensitive polymer and a therapeutic agent, which protect the agent from degradation in the stomach and release it in the intestine, using a method that avoids water-insoluble or toxic solvents and is scalable.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If proteins and peptides are delivered orally, then convenience is improved, but degradation in the stomach occurs
Solution Approach 1:
A pH-sensitive polymer coating acts as an intermediary barrier between the therapeutic protein/peptide and the harsh gastric environment. The coating remains intact at low gastric pH, protecting the therapeutic agent from degradation, and dissolves at higher intestinal pH to release the active ingredient.
Solution Approach 2:
The invention utilizes pH as a critical parameter to control the behavior of the protective coating. The pH-sensitive polymer transitions from an insoluble protective state at low pH (stomach) to a soluble releasing state at higher pH (intestine), enabling site-specific delivery.
2Reliability
If pH-sensitive polymers are used to protect therapeutic agents, then protection from gastric degradation is improved, but manufacturing complexity increases
Solution Approach 1:
The invention applies a localized protective coating only where needed - on the surface of the therapeutic agent or in immediate proximity - rather than requiring complex bulk modification of the entire formulation. This targeted approach simplifies manufacturing while maintaining protection.
3Ease of manufacture
If conventional solvent evaporation methods are used, then particle formation is achieved, but physical and chemical stability deteriorates
Solution Approach 1:
The invention employs an aqueous environment that is chemically inert and physiologically compatible, avoiding the use of organic solvents that can cause protein denaturation or chemical degradation. This maintains both physical and chemical stability of the therapeutic agent throughout the formulation process.
4Ease of manufacture
If emulsification-evaporation method is used, then microparticles are formed, but large amounts of water are required
Solution Approach 1:
The invention extracts or eliminates the need for large volumes of water and complex emulsification steps by using a direct aqueous formulation approach. The pH-sensitive polymer and therapeutic agent are formulated together in a simplified aqueous system that achieves particle formation without excessive water requirements.
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 nanoparticles provide high bioavailability and effective oral delivery of therapeutic agents by protecting them from gastric degradation and ensuring controlled release in the intestine, with less than 5% release at low pH and rapid release at neutral pH, enhancing absorption and bioavailability.
Implementation Method 1
The pH-sensitive polymer becomes soluble after gastric emptying when the drug travels to the intestine
Implementation Method 2
the drug can be released in a controlled manner in the intestine by a combination of drug dissolution and diffusion through pores in the polymer matrix
Data Source
AI summary
Formulations containing pH-sensitive nanoparticles for the enteric delivery of therapeutic agents are provided. The nanoparticles include a pH-sensitive polymer that protects the therapeutic agent against degradation in the stomach and allows it to be released in the small intestine or colon. The nanoparticle formulation is particularly effective at protecting sensitive biotherapeutic agents from degradation when administered orally, and makes it possible to avoid administration of such agents by injection. Also provided are methods for producing the formulations, as well as methods of treating diseases employing the formulations.