Polymeric Composite Matrix with High Biobased Content as Pharmaceutically Relevant Molecular Encapsulation and...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Controlled drug delivery systems (DDS) are crucial for various clinical applications, including cancer therapy.
• Developing locally implantable DDS with tunable release profiles remains a significant challenge.

Purpose of the Study:

• To design and evaluate cellulose nanocrystal (CNC)-reinforced poly(l-lactic acid) (PLA) composite beads as a locally implantable, controlled-release DDS.
• To assess the performance of these beads using doxorubicin (DOX) for triple-negative breast cancer treatment.

Main Methods:

• Fabrication of CNC-PLA composite beads using a nonsolvent-induced phase separation (NIPS) method.
• Characterization of bead properties, including mechanical stability, porosity, and water uptake.
• In vitro evaluation of DOX release kinetics at different pH values (7.4 and 5.5).
• Assessment of the anti-cancer efficacy of DOX-loaded beads on MBA-MB-231 cells and in human tissue explants.

Main Results:

• CNC loading significantly influenced the mechanical properties, porosity, water uptake, and drug release characteristics of the PLA beads.
• Composite beads exhibited pH-dependent doxorubicin release, with higher release rates at acidic pH (5.5) compared to physiological pH (7.4).
• Drug release followed Korsmeyer's kinetics, indicating diffusion and swelling as primary release mechanisms.
• DOX released from the beads effectively suppressed triple-negative breast cancer cell proliferation and induced apoptosis.

Conclusions:

• CNC-reinforced PLA composite beads represent a promising platform for programmed, locally implantable drug delivery.
• The pH-responsive release profile and demonstrated anti-cancer activity highlight the potential of this biobased DDS for targeted cancer therapy.
• Further development of these biobased platforms could lead to advanced therapeutic strategies with enhanced stability and drug delivery functions.