Abstract
Lipid vesicles (liposomes) are a unique and fascinating type of polymolecular aggregates, obtained from bilayer-forming amphiphiles—or mixtures of amphiphiles—in an aqueous medium. Unilamellar vesicles consist of one single self-closed bilayer membrane, constituted by the amphiphiles and an internal volume which is trapped by this bilayer, whereby the vesicle often is spherical with a typical desired average diameter of either about 100 nm or tens of micrometers. Functionalization of the external vesicle surface, basically achievable at will, and the possibilities of entrapping hydrophilic molecules inside the vesicles or/and embedding hydrophobic compounds within the membrane, resulted in various applications in different fields. This review highlights a few of the basic studies on the phase behavior of polar lipids, on some of the concepts for the controlled formation of lipid vesicles as dispersed lamellar phase, on some of the properties of vesicles, and on the challenges of efficiently loading them with hydrophilic or hydrophobic compounds for use as delivery systems, as nutraceuticals, for bioassays, or as cell-like compartments. Many of the large number of basic studies have laid a solid ground for various applications of polymolecular aggregates of amphiphilic lipids, including, for example, cubosomes, bicelles or—recently most successfully—nucleic acids-containing lipid nanoparticles. All this highlights the continued importance of fundamental studies. The life-saving application of mRNA lipid nanoparticle COVID-19 vaccines is in part based on year-long fundamental studies on the formation and properties of lipid vesicles. It is a fascinating example, which illustrates the importance of considering (i) details of the chemical structure of the different molecules involved, as well as (ii) physical, (iii) engineering, (iv) biological, (v) pharmacological, and (vii) economic aspects. Moreover, the strong demand for interdisciplinary collaboration in the field of lipid vesicles and related aggregates is also an excellent and convincing example for teaching students in the field of complex molecular systems.
Highlights
The aggregation behavior of biological amphiphilic lipids in the presence of water as a function of water content and temperature has been the subject of numerous fundamental investigations over the last couple of decades
One of the recent successes is the development of lipid nanoparticle (LNP)-based siRNA delivery systems [1,2] and COVID-19 vaccines containing as active ingredient a nucleoside-modified mRNA coding for the spike proteins of the COVID-19 virus (‘CO’ stands for corona, ‘VI’ for virus, and ‘D’ for disease) [3,4,5]
In this review we wanted to recall that the aggregation behavior of amphiphilic lipids in the presence of small or large amounts of an aqueous solution is fascinating, often complex and challenging to investigate, and relevant for a better understanding of certain features of living forms of matter; dispersed aqueous aggregates of amphiphilic lipids are integral parts in many applications, most notably in biomedical and cosmetic products
Summary
The aggregation behavior of biological amphiphilic lipids in the presence of water as a function of water content and temperature has been the subject of numerous fundamental investigations over the last couple of decades. In the first part of this review, we would like to recall some of the earlier pioneering investigations of the aggregation behavior of a few selected amphiphilic lipids in water (or an aqueous medium) to illustrate how the aggregation state primarily depends on the chemical structure of the amphiphile, on the amphiphile concentration, on the composition of the aqueous solution, and on temperature All this might be trivial to most of the readers, we feel, that it is worth emphasizing the importance of careful and reliable fundamental research, without which the development of many commercial products probably would not have been possible. This has recently been emphasized by piabDvhanpyrriigiodgepjDkvhelptgiisThliTcdiyjrckahtahaehktitgesaenieeroifttdbsabghne(aa2arrebfssfdo0sraigwoi1u(icsc2srm7neeoc0s)sdrditu1tpe[tuuw74nholddd)0ideonni]ei[wer:lea4mikfs“sr0tuoeyBo]fmrnmr:oankfadr“esiestefainBtuanoclrmtldartraliriesotoeeaaoienssncnlpfdleietepnrpaaaddeoclprolisreceilpeishyndcnwtal,omuiretrdetmcdhedhohrfisiilmiees,reseveseacdeer,rslurerrneectpcivlvahvhaiboiriaareeyescaltnwlwshinicztipdbhbueaaialyednrdrtyriyed.eoecaccTusatbhsabierhrstynryeciyeirooshm,nianslenfhmooiordbtoageylolmseiym,ooned”rfguesgere.o.yateacmtnT”eenmh.dshnseaaoettntlnmhmyhedyexeabaainoyemonmyneendaanlpelygryixlesimeconmosebnaanldpetegleiefihsiososnnacnritainsue,,nitspfzittusotehhrehnnodeede,-hdiagmhleynitnatleirndviessctiipglaintiaornysfitheladt coof nptorliybmutoedlecsuiglnarifliicpaindtlaysstoemoubrliecus.rrTehnet elexvaeml pofleusnddisecrustsasneddainregpoifclkipedidfrvoemsictlhees alintedraottuhreerspinoclyemwoelefeceullathraatgtghreeygaatreesaamndontghetihreamppalnicyaetixocnesllienndt,iffufenrdena-t mareenatsa.l investigations that contributed significantly to our current level of understanding of lipid vesicles and other polymolecular aggregates and their applications in different areas
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