Normally, the lipids employed for liposomes are phospholipids like phosphatidylcholine or cholesterol, that are also naturally present in cell membranes. However, other compounds can be used instead, for example, polymers or artificial surfactants (ckeck Polymeric nanoparticles) à Enlace a Polymeric nanoparticles.

Lipids have two differentiated parts. A hydrophilic or water-loving part referred to as the “head” that consists of a negatively charged phosphate group and, attached to it, two parallel uncharged fatty acid chains hang making the hydrophobic or water-hating “tail”. The special structure of the lipids is what gives them the amphiphilic properties that are essential to form emulsions and liposomes. Differences in the head and tail chemical structure, lead to the occurrence of multiple phospholipid varieties.

When they are placed in an aqueous media, the hydrophobic tails arrange together to avoid being in contact with the water, forming simple (micelles) or double (like in liposomes or cell membranes) layers and finally assembling in a spherical shape with the phospholipid heads facing outwards. This process is eased further if energy is applied like with sonication, homogenization, heating or even simply shaking.

Gene therapy: The use of genetic material as therapeutic compounds to adjust dysfunctional cell behaviors is a revolutionary approach that has gained more attention in recent years in the medical field. Up or downregulation of genetic expression leads to an increased or decreased production of proteins respectively. The main challenge that gene therapy faces with naked genetic material is the low transfection rates and thus, therapeutic efficacy. Their physical properties as big sizes and polarity, difficult the permeation thought cell and nucleus membranes as well as are susceptible to enzymatic degradation.

Liposomes and other lipid based nanovesicles are able to encapsulate DNA, RNA, siRNA, antisense oligonucleotides, aptamers, DNAzymes, plasmid DNA protecting them along the way until the cell nucleus. The main advantage over the traditional viral vectors is that there are less safety concerns regarding their use. This concept has already been applied to multiple diseases as cystic fibrosis, anemia, immune system deficiencies, viral transmissible diseases, neurological diseases, and hemophilia.

Cancer therapy: The development of highly cytotoxic drugs is needed for the success of the treatment in tumor cells. Paradoxically, the high toxicity limits its efficacy and application in vivo, causing damage to non-target organs and severe secondary effects. The use of directed liposomes has allowed the advance of many cancer drugs to preclinical and clinical trials, reducing side effects, and increasing their therapeutic index at the same time. More than 15 cancer liposomed drugs are currently clinically available.

Ocular drug delivery: The defense mechanisms observed in the eye (epithelium, tear flow and blinking reflex) hamper the drug penetration into deeper layers of the eye. The use of modified liposomes with mucoadhesive polymers and a specific lipid formula helped in overcoming these surface obstacles and reaching target areas as the conjunctival sac.

Brain drug delivery: The trespassing of the blood brain barrier is a challenge for the treatment of central nervous diseases such as Alzheimer, Parkinson, stroke, or cancer (glioma). The endothelium shows tight junctions and specialized transporters which limits the bioavailability of drugs in the central nervous system. The most invasive way of reaching the brain is directly injecting the drug in the brain through a catheter, which has many risks associated. Encapsulation of the drug in liposomes allow a non-invasive way to penetrate this barrier, since they are able to circulate, reach and permeate through it with adequate targeting strategies. Currently this is already being exploited and several liposomed central nervous system pharmaceuticals are in clinical trials or already marketed for the treatment of meningitis, pediatric brain tumors and glioblastoma with great success.

Vaccines: Antigens can be carried by liposomes, either lipids, proteins, DNA or RNA. They can also be combined with bacteria or virus components to form archaeosomes or virosomes, respectively. These vaccines have been proved to be effective in inducing immune responses and providing a sustained exposure to the antigen. More than 30 clinical trials are currently using liposomes for vaccine delivery including HIV and several types of cancer.

Immunomodulating response: The increase or decrease of a natural immune response to obtain a therapeutic result is the basis of immunotherapy. It holds great promise for the treatment of autoimmune diseases, cancer, and the prevention of transplant rejection.

During the onset of autoimmune diseases, the immune system of the host detects an endogenous substance as a threat and becomes a target. For example, β-cell proteins in Type 1 diabetes, myelin peptides in multiple sclerosis, healthy skin cell proteins and lipids in psoriasis and citrullinated proteins in rheumatoid arthritis. Phosphatidyl serine liposomes encapsulating autoantigens have been extensively used for their safe presentation to dendritic cells and stimulate immune self-tolerance. Other approaches include the encapsulation of immunosuppressive drugs or siRNA or oligonucleotides in substitution for the autoantigen.

This tactic can also be translated to the prevention of transplant rejection instead of the administration of immunosuppressives which has many risks associated including infections and cancer. The promotion of self-tolerance has not only been safer but also more successful in the long term for transplant patients.

On the contrary case is cancer, in which the body is inactive towards tumoral cells, and the immune response need to be stimulated. Some strategies include the encapsulation in liposomes of tumor associated antigens (TAAs) or nucleotides encoding for TAAs to activate a CD8+ T-cell response.

Tissue engineering: Tissue regeneration is aimed at the reconstruction of a tissue or organ that requires that cells coordinate timely and spatially to proliferate and differentiate. This comprises complex cell signaling to regulate cellular activity. The delivery of growth and differentiation factors face a rapid in vivo clearance that will benefit greatly from encapsulation in liposomes. Apart from protection, liposomes target the specific cell populations to develop in a scaffold and allow a spatio-temporal controlled delivery. Wound healing is another field in which liposomes have been used with great outlooks, specially for impaired wound healing cases, protecting short life pharmaceuticals, and accelerating neovascularization and epithelialization.