Liposomal Nanomedicine: Applications for Drug Delivery in Cancer Therapy

Abstract

The increasing prevalence of cancer, a disease in which rapid and uncontrollable cell growth causes complication and tissue dysfunction, is one of the serious and tense concerns of scientists and physicians. Nowadays, cancer diagnosis and especially its effective treatment have been considered as one of the biggest challenges in health and medicine in the last century. Despite significant advances in drug discovery and delivery, their many adverse effects and inadequate specificity and sensitivity, which usually cause damage to healthy tissues and organs, have been great barriers in using them. Limitation in the duration and amount of these therapeutic agents' administration is also challenging. On the other hand, the incidence of tumor cells that are resistant to typical methods of cancer treatment, such as chemotherapy and radiotherapy, highlights the intense need for innovation, improvement, and development in antitumor drug properties. Liposomes have been suggested as a suitable candidate for drug delivery and cancer treatment in nanomedicine due to their ability to store drugs with different physical and chemical characteristics. Moreover, the high flexibility and potential of liposome structure for chemical modification by conjugating various polymers, ligands, and molecules is a significant pro for liposomes not only to enhance their pharmacological merits but also to improve the effectiveness of anticancer drugs. Liposomes can increase the sensitivity, specificity, and durability of these anti-malignant cell agents in the body and provide remarkable benefits to be applied in nanomedicines. We reviewed the discovery and development of liposomes focusing on their clinical applications to treat diverse sorts of cancers and diseases. How the properties of liposomal drugs can be improved and their opportunity and challenges for cancer therapy were also considered and discussed.

Keywords: Cancer treatment; Drug delivery; Liposomal drugs; Nanomedicine; Therapeutic nanoparticles.

Fig. 1

Diagram of observations that led to the discovery of liposomes. The historical and scientific trends of studying behaviors of lipid and fat particles in water and the observations leading to the liposomes discovery, along with images of the scientists involved in the event, Pliny the Elder [23], Anthonie Van Hook [24], Alec D. Bangham [25], and Gerald Weissmann [26], respectively, from left to right

Fig. 2

Schematic figure of liposomes originated from lecithin. Different regions of liposomes, including hydrophilic core and hydrophobic bilayer, are demonstrated. The structure of the lecithin molecule, its hydrophilic pole, and hydrophobic chains are specified

Fig. 3

Classification of liposomes according to various criteria: a Liposomes are divided into three categories in terms of size; b The small unilamellar vesicle (SUV) structure, as a member of unilamellar vesicles (ULVs), which has a noticeable small size

Fig. 4

The general structure of the liposomes consists of phospholipid layers. Depending on the hydrophilicity–hydrophobicity of a drug, the appropriate kind of liposomes for its delivery will be determined. Hydrophilic drugs are entrapped in the central hydrophilic nucleus, and hydrophobic drugs are placed in the lipophilic area. Liposomes can also be utilized for the delivery of genes

Fig. 5

Conjugating a specific polymer such as polyethylene glycol (PEG) to liposomes. a PEGylated liposomes with PEG polymer molecules shield. b Conventional liposome trapped by antibodies and opsonins

Fig. 6

Various kinds of liposomes. a Conventional liposome; b cholesterol-conjugated liposome; c PEGylated or stealth liposome; d ligand-targeted liposome; e multi-functional liposome

Fig. 7

Mechanism of action of the drug-containing liposomes on tumor cells via EPR effect. a Healthy tissue and its normal capillaries; b cancerous tissue with increased-deformed vessels; c structure of normal and healthy vessel; d destructions and deformed capillary in tumor tissue

Fig. 8

Binding of liposomes to the target cell. a Specific attachment via ligand-receptor interaction; b non-specific absorption of liposomes through intramolecular-electrostatic forces; c the attachment and fusion of liposome to the cell membrane and drug release; d liposome arrival to the target cell and drug release without fusion; e exchange lipid fragments between the cell membrane and liposome through protein-mediated processes; f endocytosis of liposome by target cell; g lysosomal digestion of liposome in the cell cytoplasm

Fig. 9

The schematic structure of Doxil drug. Doxorubicin drug molecules are entrapped in the hydrophilic cavity of unilamellar PEGylated liposomes

Fig. 10

An overview of curcumin powder and liposomal curcumin synthesis. Chemical reactions performed for liposomal curcumin production and curcumin molecule structure in various forms are simply demonstrated