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Lipid Nanocarriers for Oligonucleotide Delivery to the Brain
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Andreia F. Jorge, Santiago Grijalvo, Alberto Pais, Ramón Eritja
Liposomes typically are composed by (i) cationic lipids, such as chol, dioleolyphosphatidylethanolamine (DOPE), dioleoyldimethylammoniumpropane (DODAP), phosphatidylcholine (PC) and unsaturated fatty acids; (ii) neutral lipids, also referred to as helper lipids; and (iii) polyethylene glycol (PEG) lipids or polysaccharides, to form a protective hydrophilic layer on the surface of liposomes and increase colloidal stability [123]. The structural features of the constitutive lipids, such as the nature and structure of head groups, length of the hydrophobic chains and the number of unsaturated alkyl chains, are also determinant to modulate the success of their transfection. Many researchers have developed libraries of newly synthesised lipid compounds to gain a better understanding of the parameters required for rationally designed, highly efficient candidates [124, 125]. To increase the efficiency in the delivery of small-molecule drugs and nucleic acids, liposomes have been properly designed with specific components which tend to respond to certain stimuli such as pH, heat, magnetic fields or light among others [126]. Extensive research has been reported with the preparation of pH-responsive liposomes as drug delivery systems. This strategy has gained increased attention due to existing differences in the pH between certain tissues and other cellular compartments. In addition, tumour tissues display ~0.5–1.0 pH values lower when compared to pH exhibited by normal tissues [127]. In this sense, liposomes made up of phosphatidylethanolamine (PE) and some derivatives like DOPE have been widely used for delivering small molecules and macromolecules. To increase long-lived circulation rates, these particles have been further modified with PEG and many other derivatives [128].
Biomimetic materials based on zwitterionic polymers toward human-friendly medical devices
Published in Science and Technology of Advanced Materials, 2022
For the development of biomimetic polymers, attention has been paid to the polar groups of phospholipid molecules present on the surfaces of cell membranes [28–30]. Figure 3 shows a schematic representation of the cell membrane structure, including various biomolecules and their functions. The cell membrane basically takes a phospholipid bilayer membrane structure; the polar groups of the phospholipid molecules that form this bilayer membrane are asymmetric [31]. Most phospholipid molecules inside the cell membrane have weakly acidic phosphatidylethanolamine or acidic phosphatidylserine as polar groups. These regulate the ion balance in the cell membrane and are responsible for the transmission of information. In contrast, phosphatidylcholine and sphingomyelin, which have a phosphorylcholine group with a neutral charge state, occupy most of the surface in contact with the extracellular aqueous phase. Glycoproteins and membrane proteins are present on the cell membrane surface, accurately capturing signal molecules from the outside and transmitting information into the cell. Currently, the non-specific capture of information molecules on the cell membrane surface causes a significant decrease in cell function and additionally generates an unfavorable biological reaction as a secondary stimulus. The normal outer membrane itself has a structure that suppresses non-specific reactions with biological components, and it is considered that the phosphorylcholine group plays a role at the functional group level [32,33]. Therefore, biomimetic polymers, in which phospholipid molecules are introduced into polymers, have been studied [34–36]. It has been found that the introduction of these polymers to surfaces of medical devices can prevent biological contamination and inhibit the reaction of biological tissues, thus extending the life of medical devices [37–41].