Polymeric Peptide Nanoparticles With Low-Burst Sustained Release
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Solution Overview
Problem
Current methods for delivering peptides and proteins face challenges such as poor absorption across epithelial membranes, rapid metabolism, and instability during formulation, leading to the need for frequent injections and inefficient encapsulation in nanoparticle systems.
Innovation Solution
The development of polymeric nanoparticles using phase inversion nanoencapsulation (PIN) with miscible solvent and non-solvent pairs to encapsulate peptides, providing low burst release and sustained delivery, with methods for micronizing peptides and tuning release profiles through Gibbs energy of mixing (ΔGmix/RT) control.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional emulsification methods are used to produce polymeric nanoparticles, then nanoparticle formation is achieved, but the secondary and tertiary structures of the peptide are destroyed and encapsulation efficiency is low
Solution Approach 1:
The patent uses a water-soluble polymer as an intermediary carrier that forms a complex with the peptide in aqueous solution, avoiding direct exposure to harsh emulsification conditions. This intermediary complex then self-assembles into nanoparticles through phase inversion, protecting the peptide structure while enabling nanoparticle formation.
Solution Approach 2:
The patent employs phase inversion (precipitation) as the core mechanism for nanoparticle formation. By controlling the phase transition of the water-soluble polymer from dissolved state to precipitated state through addition of non-solvent, nanoparticles form spontaneously without requiring harsh emulsification conditions, thus preserving peptide structure.
2Duration of action of moving object
If emulsification processes are used to encapsulate peptides in nanoparticles, then nanoparticle encapsulation is achieved, but burst release is high and sustained release is poor
Solution Approach 1:
The patent controls the release profile by changing parameters of the polymer complex formation, specifically the molecular weight and hydrophobicity of the water-soluble polymer, and the ratio of polymer to peptide. These parameter changes regulate the nanoparticle structure and drug release kinetics, achieving sustained release with minimal burst.
Solution Approach 2:
The patent performs preliminary complex formation between the water-soluble polymer and peptide in aqueous solution before nanoparticle formation. This preliminary action ensures uniform distribution and stable incorporation of the peptide into the polymer matrix, preventing burst release and enabling sustained release over extended periods.
3Quantity of substance
If traditional nanoparticle formulation methods are used, then peptide encapsulation is achieved, but oral bioavailability is poor and absorption across epithelial membranes is low
Solution Approach 1:
The patent utilizes the amphiphilic nature of the water-soluble polymer to form nanoparticle structures that can interact with biological membranes. The polymer forms a flexible shell around the peptide that facilitates membrane permeation, enabling the nanoparticle to cross epithelial barriers and achieve improved oral bioavailability.
Solution Approach 2:
The water-soluble polymer acts as an intermediary that bridges the hydrophilic peptide and the lipid membrane. Through its amphiphilic properties, the polymer facilitates the transition of the peptide across the membrane barrier, improving absorption and bioavailability while maintaining peptide stability.
4Reliability
If frequent injections are administered to maintain therapeutic levels, then peptide efficacy is maintained, but patient compliance is reduced and treatment burden increases
Solution Approach 1:
The patent designs the nanoparticle formulation with dynamic release characteristics that provide sustained therapeutic levels over extended periods. By controlling polymer degradation and peptide release kinetics, the formulation maintains therapeutic efficacy without requiring frequent injections, thereby improving patient compliance and reducing treatment burden.
Solution Approach 2:
The patent incorporates the peptide into the nanoparticle formulation in a protected and controlled manner during manufacturing. This preliminary action ensures that the peptide is released in a controlled fashion over time, maintaining therapeutic levels and reducing the need for frequent dosing adjustments.
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 method achieves low initial release (≤20% at 0 hours) and sustained release (up to 400 hours) of peptides, enabling formulations suitable for oral, intraperitoneal, nasal, and intravenous administration, with potential applications in treating type 2 diabetes.
Implementation Method 1
The PIN process is based on the mechanism of precipitation by phase inversion and thus utilizes solvent and non-solvent pairs that are completely miscible
Implementation Method 2
nanoparticles spontaneously precipitate after the immersion of a solubilized polymer solution in a non-solvent
Implementation Method 3
tuning release profiles through Gibbs energy of mixing (ΔGmix/RT) control
Data Source
AI summary
Disclosed herein are polymeric nanoparticles containing peptides, which provide low burst release and sustained, delivery of the peptides, and pharmaceutical compositions thereof. The polymeric nanoparticles contain a peptide encapsulated or dispersed therein. The nanoparticles can provide sustained release of the peptide, for example, less than 20% of the peptide is released initially (at time 0 hour) following placement into a phosphate buffered saline at pH 7.4 at 37° C. and room pressure. Methods for micronizing a peptide and for preparing polymeric nanoparticles containing solid, micronized peptides are also disclosed. The preparation methods use miscible solvent and non-solvent pairs in phase inversion nanoencapsulation processes. The Gibbs energy of mixing (ΔGMix) between the solvent and non-solvent can be tailored to achieve desired particle size, encapsulation efficiency, and release profile.