DoE-Guided Liposomal Optimization of Novel Pyrrolobenzodiazepine for Solubility and TNBC Targeting
Victor Manuel Moreno Zafra – Research Associate, King's College London; Sihan Liu – PhD student, King' s College London; Sheeba Irshad – Clinical Professor of Cancer Immunology, King's College London; Miraz Rahman – Professor of Medicinal Chemistry, King's College London; Adam Walters – Lecturer in Nanomedicine, King's College London; Khuloud Al-Jamal – Professor of Drug Delivery & Nanomedicine, King's College London /The University of Hong Kong
Dr King's College London / The National University of Malaysia, Malaysia
Introduction: Pyrrolobenzodiazepines (PBDs) are highly potent DNA-targeting anticancer agents that exert cytotoxicity via sequence-selective DNA crosslinking. Their clinical translation is limited by systemic toxicity, narrow therapeutic windows, and delivery challenges. Triple-negative breast cancer (TNBC) is an aggressive malignancy with few treatment options, creating a need for advanced delivery strategies. This study aimed to optimize a liposomal formulation of the novel PBD MH10 using Design of Experiments (DoE) to improve physicochemical properties, biodistribution, cellular uptake, and therapeutic efficacy in TNBC.
Learning Objectives:
Understand the principles of liposomal nanocarrier design for highly potent chemotherapeutics.
Explain how DoE optimizes formulation size, encapsulation efficiency, and tumour targeting.
Evaluate how liposomal delivery affects cellular uptake, drug release, stability, and antitumour efficacy.
