Poly (vinyl alcohol)/chitosan layer-by-layer microneedles for cancer chemo-photothermal therapy

• Published in: International journal of pharmaceutics 2020-02, Vol.576, p.118907-118907, Article 118907
• Main Authors: Moreira, André F., Rodrigues, Carolina F., Jacinto, Telma A., Miguel, Sónia P., Costa, Elisabete C., Correia, Ilídio J.
• Format: Article
• Language: English
• Subjects: Cancer; Combinatorial therapy; Gold-core silica shell nanorods; Layer-by-layer; Microneedles
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2019.118907

[Display omitted] •Production of Layer-by-Layer Microneedles for cancer therapy.•Microneedles promote the sequential delivery of doxorubicin and gold-silica nanorods.•Microneedles present a photothermal and pH-sensitive release profile.•Improved anti-cancer effect by the combinatorial chemo-photothermal therapy. The combination of photothermal and chemo- therapies displays a high potential to increase the efficacy of the cancer treatments or even promote their eradication. In this study, the micromoulding and electrospraying techniques were combined to produce polyvinylpyrrolidone microneedles coated with chitosan and poly (vinyl alcohol) for mediating the delivery of doxorubicin and AuMSS nanorods (Dox@MicroN) to cancer cells. The microneedles’ physicochemical characterization demonstrated that the electrospraying technique can be used to produce a layer-by-layer coating consisting of layers of doxorubicin-loaded chitosan and AuMSS enriched poly (vinyl alcohol). Further, the Dox@MicroN patches presented a good photothermal capacity leading to a temperature increase of 12 °C under near-infrared irradiation (808 nm, 1.7 W/cm−2 for 5 min), which in conjugation with the chitosan’ pH sensitivity could be used to control the doxorubicin release. Moreover, the microneedles were able to penetrate the tumor-mimicking agarose gel and promote a layer dependent drug release. Additionally, the Dox@MicroN patches’ capacity to simultaneously mediate the chemo- and photothermal-therapies rendered a superior cytotoxic effect against the cervical cancer cells. Overall, the Dox@MicroN patches demonstrated to be a simple macroscale delivery device that can be used to mediate the local administration of new drug-photothermal combinations, avoiding all the issues related to the systemic administration of anti-cancer therapeutics.