Soft Extrudable Dendritic Particles with Nanostructured Tendrils for Local Adhesion and Drug Release to Bladder...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapy

Background:

• Bladder cancer poses a significant mortality risk.
• Current intravesical drug delivery faces challenges with poor drug retention in the bladder.
• Existing high surface area nanomaterial fabrication methods are complex and costly.

Purpose of the Study:

• To develop a simple, biomimetic drug delivery platform for enhanced bladder cancer treatment.
• To create soft dendritic particles (SDPs) with improved adhesion and sustained drug release capabilities.
• To evaluate the efficacy and safety of SDPs in preclinical bladder cancer models.

Main Methods:

• Fabrication of poly(lactic-co-glycolic acid) (PLGA) based SDPs with chitosan coating using fluid flow templating.
• Encapsulation of chemotherapeutic agents (gemcitabine, docetaxel, methotrexate) within SDPs.
• Administration of SDPs via an alginate hydrogel for controlled deposition and release.
• In vitro and in vivo evaluation of SDP adhesion, drug release, cytotoxicity, and immune response in bladder cancer models.

Main Results:

• SDPs demonstrated prolonged adhesion to mouse and human cancer cells (several days).
• SDPs effectively encapsulated and released multiple chemotherapeutic drugs, showing superior in vitro cancer cell killing.
• Gemcitabine-loaded SDPs in murine models induced stronger CD45+ immune cell responses compared to controls.
• The drug delivery platform exhibited minimal toxicity in vivo.

Conclusions:

• A simple, biomimetic fluid flow templating method successfully produced adhesive SDPs for bladder cancer therapy.
• The SDP platform offers prolonged retention and controlled release of chemotherapeutics, enhancing therapeutic efficacy.
• This versatile drug delivery system shows promise for improving treatments in epithelial cancer models, particularly bladder cancer.