pH-Responsive Poly(ethylene glycol)/Poly(L-lactide) Supramolecular Micelles Based on Host-Guest Interaction

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Development of pH-responsive drug delivery systems is crucial for targeted cancer therapy.
• Supramolecular self-assembly offers a versatile platform for creating advanced nanocarriers.
• Host-guest interactions provide a mechanism for controlled drug release.

Purpose of the Study:

• To develop pH-responsive supramolecular amphiphilic micelles using poly(ethylene glycol)-benzimidazole (PEG-BM) and β-cyclodextrin-poly(L-lactide) (CD-PLLA).
• To investigate the pH-triggered dissociation and drug release characteristics of these micelles.
• To evaluate the in vitro and in vivo anticancer efficacy and pharmacokinetic profile of doxorubicin (DOX)-loaded micelles.

Main Methods:

• Supramolecular micelles formed via host-guest interaction between benzimidazole and β-cyclodextrin.
• Loading of doxorubicin (DOX) as a model anticancer drug.
• In vitro drug release studies at different pH values (7.4 vs. 5.5).
• Intracellular drug release assessment in HepG2 cells.
• In vivo studies in nude mice bearing HepG2 xenografts and pharmacokinetic studies in rats.

Main Results:

• Successfully developed pH-responsive PEG-BM/CD-PLLA supramolecular micelles.
• Micelles dissociated and accelerated DOX release in acidic conditions (pH 5.5).
• Enhanced intracellular drug release in HepG2 cells compared to pH-insensitive micelles.
• Significant tumor inhibition and reduced systemic toxicity in vivo compared to free DOX.
• Slower blood clearance rate for micellar DOX compared to free DOX.

Conclusions:

• The developed pH-responsive supramolecular micelles demonstrate effective triggered drug release.
• These nanocarriers show superior anticancer efficacy and improved safety profile in preclinical models.
• The PEG-BM/CD-PLLA supramolecular micelles represent a promising smart nanocarrier for targeted anticancer drug delivery.