A Perspective of Engineered Lipids and Liposomes: Chemical Design and Functional Application Based on Therapeutic Safety

Abstract

Liposome-based drugs have emerged as highly successful nanomedicines for clinical applications owing to their excellent biocompatibility, biodegradability, and targeting effects. However, the lipids that play a crucial role in most liposome formulations are often engineered rather than natural phospholipids. From this perspective, we outlined the classification of engineered lipids based on their material chemistry, including charged, polymerconjugated, ligand-conjugated, and choline phosphate lipids. We also discussed their drug, gene, protein, and probe delivery applications. With the increasing requirements for the innovation of nano drug excipients by the Food and Drug Administration, attention to drug efficacy and side effects has increased in clinics, and the development of superior engineered lipids has become urgent. Therefore, we aim to provide a new idea for developing engineered lipids in which lipids can be engineered with minimal chemical structure changes to achieve maximum functions enhancement, with choline phosphate lipids being a favorable choice. In the future, novel engineered lipids and liposomes should be developed with more powerful functions and superior therapeutic safety, which will allow their utilization in the diagnosis and treatment of major diseases and be valuable for more clinical applications.

Liposomes to Cubosomes: The Evolution of Lipidic Nanocarriers and Their Cutting-Edge Biomedical Applications

“…Both liposomal Dox and PEGylated liposomal Dox (PLD) demonstrated favorable toxicity profiles, with improved cardiovascular security as well as fewer alopecia, myelosuppression, vomiting, and nausea compared to conventional anthracyclines, thereby providing a better alternative for patients with risk factors for cardiovascular disease, and patients who have previously used anthracyclines . Recently choline phosphate (CP) lipids have been developed and found to have high efficacy for cancer therapy . Wang et al demonstrated Dox encapsulated CP liposomes had higher uptake and accumulated in cells compared to phosphatidyl choline (PC) loaded Dox liposomes .…”

“… 57 Recently choline phosphate (CP) lipids have been developed and found to have high efficacy for cancer therapy. 58 Wang et al demonstrated Dox encapsulated CP liposomes had higher uptake and accumulated in cells compared to phosphatidyl choline (PC) loaded Dox liposomes. 59 This further showed significantly higher cytotoxicity in cancer cells and also inhibited growth of tumor.…”

Engineered Liposomes in Interventional Theranostics of Solid Tumors

“…Liposomal drug composition has been the subject of numerous investigations for various biological purposes. − In one of the investigations, glutamic acid is successfully used as a cross-linker to conjugate polyethylene glycol (PEG) to the lipid monomer . Postadministration of PEGylated formulations/drugs results in the production of antibodies which bind to PEG selectively showing reduced treatment efficacy. − For example, PEGylated proteins and peptides demonstrate anti-PEG antibody responses by the T-cell pathway.…”