Single small molecule-assembled nanoparticles mediate efficient oral drug delivery

Area of Science:

• Nanotechnology
• Pharmacology
• Natural Products

Background:

• Oral drug delivery faces challenges due to the gastrointestinal (GI) environment and intestinal epithelium penetration.
• Medicinal natural products (MNPs) are used orally, but active compounds often lack suitable properties for oral application.
• Current simple formulation nanoparticles (NPs) have not achieved effective oral drug delivery.

Purpose of the Study:

• To investigate if MNPs contain natural nanomaterials capable of forming NPs for oral drug delivery.
• To identify small molecules from MNPs that can form NPs for enhanced drug encapsulation and GI penetration.
• To demonstrate the efficacy of a specific small molecule NP for oral disease treatment.

Main Methods:

• Screened 66 MNPs to identify small molecules forming NPs.
• Evaluated NP properties for drug encapsulation and GI penetration.
• Investigated the assembly mechanism (hydrogen bonding) and GI transport pathway (apical sodium-dependent bile acid transporter) of dehydrotrametenolic acid (DTA) NPs.

Main Results:

• Identified five classes of small molecules from MNPs that form NPs.
• Many identified NPs demonstrated efficient drug encapsulation and GI penetration capabilities.
• Dehydrotrametenolic acid (DTA) NPs were shown to mediate oral drug delivery for effective disease treatment.
• DTA NPs assemble via hydrogen bonding and utilize the apical sodium-dependent bile acid transporter for GI penetration.

Conclusions:

• Discovered a novel class of single-component, small molecule-assembled NPs for oral drug delivery.
• This finding suggests a new strategy for modernizing MNPs through nanomaterial discovery.
• The identified NPs offer a promising approach to overcome oral drug delivery limitations.