Liposomal Drug Delivery Systems and Anticancer Drugs

Abstract

Cancer is a life-threatening disease contributing to ~3.4 million deaths worldwide. There are various causes of cancer, such as smoking, being overweight or obese, intake of processed meat, radiation, family history, stress, environmental factors, and chance. The first-line treatment of cancer is the surgical removal of solid tumours, radiation therapy, and chemotherapy. The systemic administration of the free drug is considered to be the main clinical failure of chemotherapy in cancer treatment, as limited drug concentration reaches the tumour site. Most of the active pharmaceutical ingredients (APIs) used in chemotherapy are highly cytotoxic to both cancer and normal cells. Accordingly, targeting the tumour vasculatures is essential for tumour treatment. In this context, encapsulation of anti-cancer drugs within the liposomal system offers secure platforms for the targeted delivery of anti-cancer drugs for the treatment of cancer. This, in turn, can be helpful for reducing the cytotoxic side effects of anti-cancer drugs on normal cells. This short-review focuses on the use of liposomes in anti-cancer drug delivery.

Keywords: anticancer drugs; drug delivery; liposomes.

Figure 1

Structure of conventional and functionalised liposomes: (A) conventional liposomes comprising phospholipids; (B) PEGylated/stealth liposomes containing a layer of polyethylene glycol (PEG); (C) targeted liposomes containing a specific ligand to target a cancer site; and (D) multifunctional liposomes, which can be used for diagnosis and treatment of solid tumours. Adapted from Creative Commons Attribution License [55].

Figure 2

Passive (A) and (B) active targeting of nanocarriers. Nanocarriers reach tumours selectively through the leaky vasculature, or in other cases, where the nanocarrier size determines the retention in the tumour tissue. Drugs in the absence of nanocarriers diffuse freely in and out the tumour blood vessels due to their small size, and therefore their effective concentrations in the tumour decrease rapidly. The EPR effect is where drug-loaded nanocarriers cannot diffuse back into the blood stream due to their large size, resulting in progressive accumulation. In active targeting, ligands grafted at the surface of nanocarriers bind to receptors (over)expressed by cancer cells or to angiogenic endothelial cells. Adapted and reproduced with permission [3].

Figure 3

(A) Confocal laser scanning micrograph showing the interaction between fluorescein-labeled liposomes and FRO cells after 6 h incubation (bar = 35 μm) and (B) intracellular uptake of ATRA as free form or entrapped in liposomes within FRO cells as a function of the incubation time. Reproduced with permission [16]. * p < 0.05, ** p < 0.01.

Figure 4

Imaging and release rates of paclitaxel (PCX) liposomes: (A) transmission electron microscopy images of PCX liposomes and targeting PCX liposomes, (B) atomic force microscopy images of PCX liposomes and targeting PCX liposomes, and (C) release rates (%) of PCX-loaded liposomes in the release media of pH 7.4 PBS containing 10% fetal bovine serum (mean ± standard deviation (n = 3). Reproduced with permission [30].