Enhancing Doxorubicin Bioavailability via Dissolving Microneedles: Roles of Drug Loading and Administration Force.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Systemic doxorubicin (DOX) administration for breast cancer causes severe side effects.
• Local drug delivery strategies are needed to improve therapeutic efficacy and reduce toxicity.

Purpose of the Study:

• To develop and characterize doxorubicin-loaded dissolving microneedles (DOX-MN) for localized breast cancer treatment.
• To investigate the impact of drug loading and application force on DOX bioavailability and therapeutic outcomes.
• To evaluate the in vivo antitumor efficacy and safety of the DOX-MN patch.

Main Methods:

• Fabrication of DOX-MN using centrifugal micro-molding.
• Characterization of MN mechanical properties, skin insertion, and dissolution profiles.
• In vivo pharmacokinetic studies in a 4T1 tumor-bearing mouse model.
• Assessment of tumor inhibition rates and skin irritation.

Main Results:

• DOX-MN patches were successfully fabricated with drug enrichment at needle tips, rapid dissolution, and good skin insertion.
• High drug loading and optimal application force (25 N) significantly enhanced DOX bioavailability (65.25%) and reduced skin residue.
• DOX-MN demonstrated potent antitumor efficacy (90.61% tumor inhibition) comparable to intravenous injection with reduced local irritation.

Conclusions:

• Optimized drug loading and application force are critical for efficient local DOX delivery via microneedles.
• DOX-MN patches offer a promising strategy for localized breast cancer therapy, enhancing efficacy and minimizing systemic toxicity.
• This approach presents a novel, safer alternative to conventional doxorubicin administration for breast cancer treatment.