Printed cisplatin on microneedle arrays for transdermal delivery enhances olaparib-induced synthetic lethality in a mouse model of homologous recombination deficiency

Abstract

Small molecule inhibitors targeting specific proteins are claiming a continuously growing share in cancer therapy, more commonly in combination with traditional chemotherapeutic drugs. While these inhibitors are taken orally, the majority of chemotherapies are administered through intravenous injection in the hospital premises. Alternative routes for chemotherapy administration would allow more frequent administration at lower dosing by the patient oneself, allowing combination treatment with reduced side effects. Here, we employed laser printing to prepare microneedles for transdermal delivery of cisplatin. Combination treatment with cisplatin transdermally and the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib orally leads to effective treatment in a cancer xenograft mouse model in vivo, while reducing the risk for systemic side effects. This work opens new avenues in anti-cancer therapy by allowing the administration of chemotherapy without the need for intravenous injection alone or in combination with other therapies.