Chitosan-Liposomes Coated 3D-Printed Microneedles for Enhanced Transdermal Drug Delivery

Abstract

Breast cancer remains one of the most commonly diagnosed malignancies among women and one of the leading causes of cancer-related mortality. Although treatment options have advanced, systemic chemotherapy remains limited by nonspecific drug distribution and toxicity to healthy tissues. Transdermal drug delivery offers a minimally invasive alternative, but drug penetration through the skin is restricted by the stratum corneum. Combining liposomal nanocarriers with microneedles can help overcome this barrier, potentially enabling more localized and effective drug delivery. This study developed a 3D-printed solid microneedle platform coated with a chitosan film containing cisplatin-loaded liposomes as a potential therapeutic approach for triple negative breast cancer (TNBC). TNBC is an aggressive breast cancer subtype, characterized by poor prognosis, high risk of metastasis, and limited targeted treatment options. Following compression testing, microneedles showed adequate mechanical performance for skin insertion (> 0.058 N/Needle), while plasma etching improved the wettability of the biocompatible resin, facilitating chitosan coating. The cisplatin-loaded liposomes were manufactured using the extrusion method and characterized by dynamic light scattering. They had a mean particle size of 132.4 nm and an entrapment efficiency of 70.64 ± 7.32%, with particle size and PDI remaining stable for three weeks when stored at room temperature. Biological evaluation showed that the Bio MN + chitosan formulation maintained HaCaT (immortalized human epidermal keratinocyte) cell viability at 68 ± 3.51% 24 h (p-value = 0.13), while cisplatin-loaded liposomes produced concentration- and time-dependent cytotoxicity in MDA-MB-231 cells, reducing cell viability at 24, 48 and 72h, and reaching 6.10 ± 0.66% at 50 µM after 72 h (p-value < 0.0001). Overall, the developed system demonstrates the feasibility of integrating 3D-printed microneedles, chitosan coatings, and liposomal cisplatin into a single localized drug delivery platform. While microneedle-based platforms have previously been explored for dermatological treatments, this study introduces their application in localized drug delivery for cancer therapy, highlighting the versatility of the platform beyond conventional skin-focused uses. Future work will focus on in vivo evaluation to assess skin insertion, local drug delivery, therapeutic efficacy in TNBC, biocompatibility, and systemic safety.