Doxorubicin loaded salicylic acid crosslinked chitosan nanoparticles as postsurgical implants for breast cancer

Surgical resection remains a primary intervention for breast cancer; however, the risk of recurrence necessitates adjuvant systemic chemotherapy, which is often associated with severe side effects. To address this, we developed doxorubicin (Dox)-loaded salicylic acid (SA)-crosslinked chitosan (CH) nanoparticles (Dox-SA-CH-NPs) as a localized post-surgical implant to minimize systemic toxicity and improve therapeutic efficacy. Dox was encapsulated within a CH matrix crosslinked with SA, and the resulting nanoparticles were compared with tripolyphosphate (TPP)-crosslinked CH nanoparticles (Dox-CH-TPP-NPs). Dox-SA-CH-NPs exhibited a mean particle size of 110.9 ± 0.2 nm, a zeta potential of 33.25 ± 0.2 mV, encapsulation efficiency of 93.4 ± 0.01 %, and a drug loading capacity of 13.81 ± 0.1 %. Drug release from Dox-SA-CH-NPs was sustained (48.05 ± 2.3 % over 72 h), and lower than that observed with Dox-CH-TPP-NPs (64 ± 2.7 %). Based on release kinetics and cytotoxicity assays, Dox-SA-CH-NPs were selected for further investigation. In vitro and in vivo studies confirmed accelerated tissue regeneration ability in SA-CH-NPs and effective tumour inhibition by Dox-SA-CH-NPs. Notably, higher collagen deposition was observed on days 4 and 9 in the SA-CH-NP-treated group. These findings highlight the potential of Dox-SA-CH-NPs as a promising localized chemotherapy strategy to improve post-surgical outcomes in breast cancer treatment.