Abstract:
In the last decade, advances in cancer research have reached a phenomenal level, with new and improved chemotherapeutic treatment options available for people living with cancer. Despite the spectrum of potential anticancer agents, their clinical outcomes have been limited by severe side effects. In this context, nanocarrier delivery systems have emerged for improving site-specific delivery, cellular uptake and intracellular stability, while minimizing drug degradation and inactivation upon administration. Liposomes are bilayered phospholipid vesicles which have received much interest in the past few decades as drug and gene delivery systems; consequently, some liposomal formulations have been approved for clinical trials and even marketed for therapeutic use (e.g., Doxil®/Caelyx®). pH-sensitive liposomes have been used as an alternative to conventional liposomes in effective targeted intracellular delivery of anticancer drugs. Composed of pH-sensitive phospholipids, these liposomes destabilize under acidic conditions to release the encapsulated contents. The research has focused on using low pH as endogenous triggers to release the payload from liposomes extracellularly or intracellularly by exploiting the acidity in the tumoral interstitium (pH 6.8) or endosomes (pH < 6), respectively. More recent research in cancer drug delivery has focused on combining favourable properties of pH-responsiveness, longevity and specific targeting ability to effectively deliver contents into the cytoplasm of cancer cells. This is achieved by utilizing new lipid constructs that confers pH-responsiveness, and introducing hydrophilicity and ligand to the surface of liposomes. In this review, the development rationales and structural types of pH-sensitive liposomes will be discussed. The focus will be on the recent advances in pH-sensitive liposomes for tumor targeted anticancer drug delivery, as research in this area has grown exponentially in the past decade. The chapter will also present the challenges in advancing pH-sensitive liposomes to clinical application including the techniques to load various drug molecules into the pH-sensitive liposomes.