Local delivery of antineoplastic agents by controlled-release polymers for the treatment of malignant brain tumours

Shaan M Raza The Johns Hopkins University School of Medicine, Department of Neurological Surgery, 600 N. Wolfe Street, Meyer 7-113, Baltimore, MD 21287, USA. [email protected]

Gustavo Pradilla The Johns Hopkins University School of Medicine, Department of Neurological Surgery, 600 N. Wolfe Street, Meyer 7-113, Baltimore, MD 21287, USA. [email protected]

Federico G Legnani The Johns Hopkins University School of Medicine, Department of Neurological Surgery, 600 N. Wolfe Street, Meyer 7-113, Baltimore, MD 21287, USA. [email protected]; Ospedale San Gerardo, Monza, Italy

Quoc Anh Thai The Johns Hopkins University School of Medicine, Department of Neurological Surgery, 600 N. Wolfe Street, Meyer 7-113, Baltimore, MD 21287, USA. [email protected]

Alessandro Olivi The Johns Hopkins University School of Medicine, Department of Neurological Surgery, 600 N. Wolfe Street, Meyer 7-113, Baltimore, MD 21287, USA. [email protected]; The Johns Hopkins University School of Medicine, Department of Ophthalmology, Baltimore, Maryland, USA

Jon D Weingart The Johns Hopkins University School of Medicine, Department of Neurological Surgery, 600 N. Wolfe Street, Meyer 7-113, Baltimore, MD 21287, USA. [email protected]; The Johns Hopkins University School of Medicine, Department of Oncology, Baltimore, Maryland, USA

Henry Brem The Johns Hopkins University School of Medicine, Department of Neurological Surgery, 600 N. Wolfe Street, Meyer 7-113, Baltimore, MD 21287, USA. [email protected]

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Abstract

Recent advances in the treatment of malignant brain tumours have focused on the development of targeted local delivery of therapeutic agents, which combine various antineoplastic strategies that include cytotoxic, anti-angiogenic and immunomodulatory mechanisms, among others. The introduction of local delivery devices for sustained administration of antineoplastic agents represents a new opportunity to effectively treat these malignancies by facilitating the intracranial administration of safe and clinically efficacious doses for prolonged periods of time in a controlled fashion. This technology circumvents the need for high systemic doses with potentially harmful toxicities, bypasses the blood–brain barrier and can be tailored to deliver new agents with complex pharmacological properties. Based on local delivery strategies, new delivery systems, including convection-enhanced delivery and microchips, have been developed. As a result, recent advances in tumour biology have been adopted as potentially translatable treatments and are undergoing preclinical and clinical evaluation at present. These novel approaches could improve the prognosis of patients with these tumours.

Keywords

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