Exploring release mechanisms by disrupting π-π stacking regions in stable micelles

Area of Science:

• Polymer Chemistry
• Materials Science
• Nanotechnology

Background:

• π-π stacking enhances delivery platform stability but limits drug release.
• Disrupting π-π stacking via structural rearrangements is key to improving drug release.
• Existing crosslinking strategies often struggle with complete drug dissolution.

Purpose of the Study:

• To synthesize and characterize novel block copolymer micelles (PHB) for enhanced drug delivery.
• To investigate the drug release mechanism of PHB-based micelles, focusing on structural rearrangements.
• To evaluate the synergistic effects of crosslinking and esterase-responsive strategies on drug release.

Main Methods:

• Synthesis of poly(3-(isobutyloxy)-2-oxopropyl benzoate)-b-poly(2-hydroxybutyl methacrylate)-co-poly((ethylene glycol)methylether methacrylate) [PBOOPMA-b-P(HBMA-co-PEGMA), PHB] micelles.
• Utilizing micellar dissolutions to quantify early drug release improvements.
• Employing an esterase-responsive strategy to induce micellar reassembly and structural changes.
• Assessing biosafety and drug cytotoxicity (IC50) of the developed nanocarrier (PHB-EDE@CPT).

Main Results:

• Crosslinking-induced structural rearrangements improved early drug release by 43-55%.
• The esterase-responsive strategy induced 77-79% size variation, intensifying structural rearrangements.
• Combined crosslinking and esterase-responsive strategies synergistically enhanced drug release.
• Validated biosafety (95.81% at 400 mg L⁻¹) and drug cytotoxicity (IC50 ≈ 2.5 mg L⁻¹).

Conclusions:

• Responsive modulation of π-π stacking regions via crosslinking and esterase-responsiveness significantly enhances drug release.
• The developed PHB-based crosslinked micelles demonstrate promising potential for drug delivery applications.
• Further research into responsive modulation strategies for π-π stacking regions is warranted.