Thiolated mPEG-PLA-CS-MBI Nanoparticles for Mucosal Adhesion
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Solution Overview
Problem
Thiolated polymers used as hydrophobic drug carriers exhibit weak reactions with drug molecules, leading to quick release and low encapsulation efficiency, limiting their application in sustained drug delivery.
Innovation Solution
Synthesis of thiolated mPEG-PLA-CS-MBI nanoparticles through stepwise synthesis, where methoxy polyethylene glycol forms a polymer with polylactic acid and chitosan, which is then sulfhydrylated using 5-amino-2-mercapto benzimidazole to create a thiolated polymer capable of forming disulfide bonds with mucosal membranes for enhanced adhesion and sustained drug release, and forming a core-shell structure to evade the reticuloendothelial system.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If thiolated polymers are used as hydrophobic drug carriers, then adhesion ability to mucosal membrane is enhanced, but reaction with hydrophobic drug molecules is weak causing quick release and low encapsulation efficiency
Solution Approach 1:
The patent creates a composite nanoparticle system combining thiolated chitosan (for adhesion), mPEG-PLA (for drug loading and stability), and emodin (hydrophobic drug). This composite structure allows the thiolated chitosan to provide strong mucosal adhesion while the mPEG-PLA core effectively encapsulates hydrophobic drugs through hydrophobic interactions, resolving the contradiction between adhesion ability and encapsulation efficiency
Solution Approach 2:
The nanoparticle is designed with differentiated functional regions: the thiolated chitosan forms the outer shell providing adhesion functionality, while the mPEG-PLA forms the inner core providing drug loading capability. This local quality differentiation allows each component to optimize its specific function without interfering with the other, achieving both strong adhesion and high encapsulation efficiency
2Reliability
If thiolated polymers are used as drug carriers, then adhesion to mucosal membrane is improved, but drug release is quick and unsustainable
Solution Approach 1:
The nanoparticle system employs dynamic control of drug release through the gradual oxidation of thiol groups to disulfide bonds at the mucosal site. This dynamic process allows the particles to maintain structural integrity during circulation, adhere strongly to the mucosal membrane, and then sustain drug release over time as the disulfide bonds form and the polymer matrix slowly degrades in the physiological environment
3Reliability
If mPEG forms core-shell structure micelle on nanoparticle surface, then protection from reticuloendothelial system is achieved, but circulation time is prolonged requiring sustained release capability
Solution Approach 1:
The patent utilizes parameter changes in the polymer structure, specifically the molecular weight and composition ratio of mPEG-PLA, to optimize the core-shell micelle formation. The mPEG shell provides steric stabilization and evades reticuloendothelial clearance, while the PL A core maintains appropriate hydrophobicity for drug loading. The thiolation degree of chitosan is also optimized to balance adhesion strength and sustained release characteristics over the prolonged circulation period
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 thiolated nanoparticles achieve enhanced adhesion to mucosal membranes, prolonging drug residence time, facilitating sustained release and improving encapsulation efficiency and drug loading capacity, while preventing clearance by the reticuloendothelial system for prolonged circulation in vivo.
Implementation Method 1
The thiolated polymer forms a disulfide bond to adhere to the surface of a mucosal membrane through thiol oxidation
Implementation Method 2
thiomers can form disulfide bonds with mucosal layers, and generate specific binding with the cysteine-rich subdomains of the mucoproteins
Implementation Method 3
the mPEG may form a core-shell structure micelle on the surface of the composite to prevent the nano-composite from being identified and cleared by the reticuloendothelial system
Implementation Method 4
the reaction between the thiolated polymers and the hydrophobic drug molecules
Data Source
AI summary
The invention relates to a preparation method of new-type nanoparticles for loading emodin, which comprises: using L.A, mPEG and stannous iso caprylate to synthesize a first intermediate product; using the first intermediate product, butanedioic anhydride and 4-dimethylaminopyridine to synthesize a second intermediate product; using the second intermediate product, 1-ethyl-(3-dimethylamino propyl) carbodiimide hydrochloride, N-hydroxysuccinimide and chitosan to synthesize a third intermediate product; using the third intermediate product and sodium periodate to synthesize a fourth intermediate product; using the fourth intermediate product and 5-amino-2-mercapto benzimidazole to synthesize the new-type thiolated nanoparticles. The nanoparticles loaded with emodin are used for intestinal tract dose, which may enhance the nanoparticles' adhesion ability, prolong residence time of drugs on mucosal membranes, and facilitate sustained-release of drug molecules. The encapsulation efficiency after loading drugs is no less than 83.6%, the drug loading capacity is no less than 3.89%, and good water solubility and biological degradability are provided.