810:, but during the 2010s, the earlier research into using LNPs for siRNA became a foundation for new research into using LNPs for mRNA. Lipids intended for short siRNA strands did not work well for much longer mRNA strands, which led to extensive research during the mid-2010s into the creation of novel ionizable cationic lipids appropriate for mRNA. As of late 2020, several mRNA vaccines for SARS-CoV-2 use LNPs as their drug delivery system, including both the Moderna COVID-19 vaccine and the Pfizer–BioNTech COVID-19 vaccines.
616:, as well as in other disciplines. Due to their unique size-dependent properties, lipid nanoparticles offer the possibility to develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could hold great promise for attaining the bioavailability enhancement along with controlled and site-specific drug delivery. SLN's are also considered to well tolerated in general, due to their composition from physiologically similar lipids.
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targeting, increased drug stability and no problems with respect to large scale production. Furthermore, various functions such as molecules for targeting, PEG chains for stealth properties or thiol groups for adhesion via disulfide bond formation can be immobilized on their surface. A recent study has demonstrated the use of solid lipid nanoparticles as a platform for oral delivery of the nutrient mineral
109:
61:
736:, protection of sensitive drug molecules from the outer environment water, light) and even controlled release characteristics were claimed by the incorporation of poorly water-soluble drugs in the solid lipid matrix. Moreover, SLN can carry both lipophilic and hydrophilic drugs and are more affordable compared to polymeric/surfactant-based carriers.
579:(for structure). Because of rapid clearance by the immune system of the positively charged lipid, neutral ionizable amino lipids were developed. A novel squaramide lipid (that is, partially aromatic four-membered rings, which can participate in pi–pi interactions) has been a favored part of the delivery system used, for example, by Moderna.
775:
developed ionizable cationic lipids which are "positively charged at an acidic pH but neutral in the blood." Cullis also led the development of a technique involving careful adjustments to pH during the process of mixing ingredients in order to create LNPs which could safely pass through the cell
619:
The conventional approaches such as use of permeation enhancers, surface modification, prodrug synthesis, complex formation and colloidal lipid carrier-based strategies have been developed for the delivery of drugs to intestinal lymphatics. In addition, polymeric nanoparticles, self-emulsifying
595:
The obtained LNP formulation can subsequently be filled into sterile containers and subjected to final quality control. However, various measures to monitor and evaluate product quality are integrated in every step of LNP manufacturing and include testing of polydispersity, particle size, drug
648:
drug delivery approaches. It has been proposed that SLNs combine numerous advantages over the other colloidal carriers i.e. incorporation of lipophilic and hydrophilic drugs feasible, no biotoxicity of the carrier, avoidance of organic solvents, possibility of controlled drug release and drug
700:
and yielded some promising results. SLNs have been looked at as a potential drug carrier system since the 1990s. SLNs do not show biotoxicity as they are prepared from physiological lipids. SLNs are especially useful in ocular drug delivery as they can enhance the
870:
cell monolayer could be alternative tissue for development of an in-vitro model to be used as a screening tool before animal studies are undertaken. The results obtained in this model suggested that the main absorption mechanism of carvedilol loaded solid lipid
681:
as a lipid and surfactant, respectively. Another example of drug delivery using SLN would be oral solid SLN suspended in distilled water, which was synthesized to trap drugs within the SLN structure. Upon indigestion, the SLNs are exposed to
523:
An SLN is generally spherical in shape and consists of a solid lipid core stabilized by a surfactant. The core lipids can be fatty acids, acylglycerols, waxes, and mixtures of these surfactants. Biological membrane lipids such as
1884:
Shah, Mansi K.; Madan, Parshotam; Lin, Senshang (June 2014). "Preparation, in vitro evaluation and statistical optimization of carvedilol-loaded solid lipid nanoparticles for lymphatic absorption via oral administration".
591:
is possible using ultrasonification at the cost of long sonication time. Solvent-emulsification is suitable in preparing small, homogeneously sized lipid nanoparticles dispersions with the advantage of avoiding heat.
67:
are ("hollow") lipid nanoparticles which have a phospholipid bilayer as coat, because the bulk of the interior of the particle is composed of aqueous substance. In various popular uses, the optional payload is e.g.
1443:
Shah, Mansi K.; Madan, Parshotam; Lin, Senshang (23 May 2013). "Preparation, evaluation and statistical optimization of carvedilol-loaded solid lipid nanoparticle for lymphatic absorption via oral administration".
1922:
Shah, Mansi K.; Madan, Parshotam; Lin, Senshang (3 October 2015). "Elucidation of intestinal absorption mechanism of carvedilol-loaded solid lipid nanoparticles using Caco-2 cell line as an in-vitro model".
1617:
Mukherjee, S et al. “Solid lipid nanoparticles: a modern formulation approach in drug delivery system.” Indian journal of pharmaceutical sciences vol. 71,4 (2009): 349-58. doi:10.4103/0250-474X.57282
1809:
Shah, Mansi K.; Madan, Parshotam; Lin, Senshang (29 July 2014). "Elucidation of intestinal absorption mechanism of carvedilol-loaded solid lipid nanoparticle using Caco-2 cell line as an model".
784:. The acidity inside the endosomes causes LNPs' ionizable cationic lipids to acquire a positive charge, and this is thought to allow LNPs to escape from endosomes and release their RNA payloads.
587:
Different formulation procedures include high shear homogenization and ultrasound, solvent emulsification/evaporation, or microemulsion. Obtaining size distributions in the range of 30-180
720:
Advantages of SLNs include the use of physiological lipids (which decreases the danger of acute and chronic toxicity), the avoidance of organic solvents, a potential wide application spectrum (
1231:
Wolfgang
Mehnert, Karsten Mäder, Solid lipid nanoparticles: Production, characterization and applications, Advanced Drug Delivery Reviews, Volume 64, 2012, Pages 83-101, ISSN 0169-409X,
468:(emulsifiers). The emulsifier used depends on administration routes and is more limited for parenteral administrations. The term lipid is used here in a broader sense and includes
1522:
Arana, Lide; Salado, Clarisa; Vega, Sandra; Aizpurua-Olaizola, Oier; Arada, Igor de la; Suarez, Tatiana; Usobiaga, Aresatz; Arrondo, José Luis R.; Alonso, Alicia (2015-11-01).
44:
Solid lipid nanoparticles (SLNs). There is only one phospholipid layer because the bulk of the interior of the particle is composed of lipophilic substance. Payloads such as
992:
Jenning, V; ThĂĽnemann, AF; Gohla, SH (2000). "Characterisation of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipids".
645:
516:(with respect to charge and molecular weight) have been used to stabilize the lipid dispersion. It has been found that the combination of emulsifiers might prevent
628:, micellar solutions and recently solid lipid nanoparticles (SLN) have been exploited as probable possibilities as carriers for oral intestinal lymphatic delivery.
756:
in the mid-1980s, Philip
Felgner pioneered the use of artificially-created cationic lipids (positively-charged lipids) to bind lipids to nucleic acids in order to
1855:
Müller, Rainer H.; Mäder, Karsten; Gohla, Sven (3 July 2000). "Solid lipid nanoparticles (SLN) for controlled drug delivery – a review of the state of the art".
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membranes of living organisms. As of 2021, the current understanding of LNPs formulated with such ionizable cationic lipids is that they enter cells through
670:
608:
is one of the emerging fields of lipid nanotechnology (for a review on lipid nanotechnology, see ) with several potential applications in drug delivery,
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and the solid state of the lipid permit better controlled drug release due to increased mass transfer resistance. Shah et al. in their book
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2012:
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567:) are made of four types of lipids: an ionizable cationic lipid (whose positive charge binds to negatively charged mRNA), a
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1033:
431:
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Pandey, Rajesh; Sharma, Sadhna; Khuller, G.K. (2005). "Oral solid lipid nanoparticle-based antitubercular chemotherapy".
1288:
evaluation. Rawat MK, Jain A and Singh S, Journal of
Pharmaceutical Sciences, 2011, volume 100, issue 6, pages 2366-2378
1193:"Discovery of a Novel Amino Lipid That Improves Lipid Nanoparticle Performance through Specific Interactions with mRNA"
183:
17:
806:
By that point in time, siRNA drug developers like
Alnylam were already looking at other options for future drugs like
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1716:
1689:
640:. SLNs combine the advantages of lipid emulsion and polymeric nanoparticle systems while overcoming the temporal and
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2005:
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56:, cell-targeting peptides, and/or other drug molecules can be bound to the exterior surface of the SLN.
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cell line as in vitro model was developed. Several researchers have shown the enhancement of oral
732:) and the high pressure homogenization as an established production method. Additionally, improved
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807:
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1978:
1400:"A novel approach to oral iron delivery using ferrous sulphate loaded solid lipid nanoparticles"
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Hock, N; Racaniello, GF; Aspinall, S; Denora, N; Khutoryanskiy, V; Bernkop-SchnĂĽrch, A (2022).
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or others can be embedded in the interior, as desired. Optionally, targeting-molecules such as
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1351:"Thiolated Nanoparticles for Biomedical Applications: Mimicking the Workhorses of our Body"
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1792:"COVID-19: Vancouver's Acuitas Therapeutics a key contributor to coronavirus solution"
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Pardi, Norbert; Hogan, Michael J.; Porter, Frederick W.; Weissman, Drew (April 2018).
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From 2005 into the early 2010s, LNPs were investigated as a drug delivery system for
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544:(cholesterol) are utilized as stabilizers. Biological lipids having minimum carrier
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Fam, SY; Chee, CF; Yong, CY; Ho, KL; Mariatulqabtiah, AR; Tan, WS (April 2020).
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Studies on binary lipid matrix-based solid lipid nanoparticles of repaglinide:
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sterilization, a necessary step towards formulation of ocular preparations.
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Solid lipid nanoparticles can function as the basis for oral and parenteral
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1269:; Mashaghi, A. Lipid Nanotechnology. Int. J. Mol. Sci. 2013, 14, 4242-4282.
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experiments that this use of cationic lipids had undesired side effects on
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525:
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469:
383:
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73:
1270:
1166:"Without these lipid shells, there would be no mRNA vaccines for COVID-19"
1524:"Solid lipid nanoparticles for delivery of Calendula officinalis extract"
1316:
1077:
880:
876:
799:'s siRNA drugs. In 2018, the FDA approved Alnylam's siRNA drug Onpattro (
795:
to commercialize his LNP research; Acuitas worked on developing LNPs for
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49:
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402:. LNPs as a drug delivery vehicle were first approved in 2018 for the
53:
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Cornebise, Mark; Narayanan, Elisabeth; Xia, Yan (November 12, 2021).
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the latter into cells. However, by the late 1990s, it was known from
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588:
461:
447:
159:
77:
1246:"Lipid nanoparticle (LNP) manufacturing: Challenges & Solutions"
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drugs. Solid lipid nanoparticles have another advantage of allowing
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752:—meaning they do not easily mix with each other. While working at
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absorption of drugs and improve the ocular bioavailability of both
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delivery. To elucidate the absorption mechanism, from solid lipid
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is that in nature, lipids and nucleic acids both carry a negative
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lipid nanoparticles as their delivery vehicle (including both the
335:
1990:
925:
898:
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of poorly water-soluble drugs when encapsulated in solid lipid
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A significant obstacle to using LNPs as a delivery vehicle for
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Pharmaceutical
Perspectives of Nucleic Acid-Based Therapeutics
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that dissolve the SLNs and release the drugs into the system.
505:
451:
403:
387:
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907:, lipid bilayer shell, an earlier form with some limitations
791:(siRNA) drugs. In 2009, Cullis co-founded a company called
1300:"Stealth Coating of Nanoparticles in Drug-Delivery Systems"
803:), the first drug to use LNPs as the drug delivery system.
650:
644:
stability issues that troubles the conventional as well as
419:
108:
60:
1632:"The first Covid-19 vaccines have changed biotech forever"
842:
absorption mechanism from solid lipid nanoparticles using
814:
uses its own proprietary ionizable cationic lipid called
1741:"Lipid Nanoparticle Systems for Enabling Gene Therapies"
1059:
1857:
European
Journal of Pharmaceutics and Biopharmaceutics
1034:"How nanotechnology helps mRNA Covid-19 vaccines work"
771:
During the late 1990s and 2000s, Pieter Cullis of the
669:-loaded solid lipid nanoparticles were prepared using
410:. LNPs became more widely known in late 2020, as some
1190:
991:
1571:"Solid lipid nanoparticles for ocular drug delivery"
693:
Many nano-structured systems have been employed for
1739:Cullis, Pieter R.; Hope, Michael J. (5 July 2017).
1486:
1684:. London: Taylor & Francis. pp. 273–303.
1663:UC San Diego Library: San Diego Technology Archive
833:
2310:
1854:
913:, a complex of plasmid or linear DNA and lipids
1698:
1569:Seyfoddin, Ali; J. Shaw; R. Al-Kassas (2010).
2006:
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446:with an average diameter between 10 and 1000
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1442:
826:licensed an ionizable cationic lipid called
653:, by incorporating the hydrophilic molecule
450:. Solid lipid nanoparticles possess a solid
1732:
1680:. In Mahato, Ram I.; Kim, Sung Wan (eds.).
1630:Foley, Katherine Ellen (22 December 2020).
2013:
1999:
1738:
1665:. Regents of the University of California.
1233:https://doi.org/10.1016/j.addr.2012.09.021
1102:
1062:"mRNA vaccines — a new era in vaccinology"
958:
879:and, more specifically, clathrin-mediated
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353:
1925:Pharmaceutical Development and Technology
1887:Pharmaceutical Development and Technology
1811:Pharmaceutical Development and Technology
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1446:Pharmaceutical Development and Technology
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596:loading efficiency and endotoxin levels.
1659:"Phil Felgner Interview – July 22, 1997"
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1711:. Boca Raton: CRC Press. p. 191.
1528:Colloids and Surfaces B: Biointerfaces
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994:International Journal of Pharmaceutics
1994:
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1032:Cooney, Elizabeth (1 December 2020).
2267:
1678:"Cationic lipid-based gene delivery"
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392:pharmaceutical drug delivery system
24:
2020:
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1790:Shore, Randy (November 17, 2020).
1433:
1237:
673:technique for oral delivery using
464:. The lipid core is stabilized by
442:A lipid nanoparticle is typically
437:
25:
2335:
1960:
1244:Marciniak, Mike (June 21, 2023).
432:Pfizer–BioNTech COVID-19 vaccines
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2279:
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1967:
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661:) in a lipid matrix composed of
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520:agglomeration more efficiently.
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1170:Chemical & Engineering News
599:
95:Part of a series of articles on
1540:10.1016/j.colsurfb.2015.07.020
1398:Zariwala, MG (November 2013).
1131:
1122:
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985:
952:
834:Lymphatic absorption mechanism
773:University of British Columbia
13:
1:
2214:Scanning tunneling microscope
1869:10.1016/S0939-6411(00)00087-4
1419:10.1016/j.ijpharm.2013.08.070
1197:Advanced Functional Materials
1164:Cross, Ryan (March 6, 2021).
1066:Nature Reviews Drug Discovery
1006:10.1016/S0378-5173(00)00378-1
946:
778:receptor-mediated endocytosis
2319:Nanoparticles by composition
1937:10.3109/10837450.2014.938857
1899:10.3109/10837450.2013.795169
1823:10.3109/10837450.2014.938857
1657:Jones, Mark (22 July 1997).
1588:10.3109/10717544.2010.483257
1458:10.3109/10837450.2013.795169
582:
418:technology coat the fragile
7:
2186:Molecular scale electronics
1758:10.1016/j.ymthe.2017.03.013
1172:. American Chemical Society
969:10.1007/978-1-4020-5041-1_3
886:
604:Development of solid lipid
10:
2340:
1708:Liposomes in Gene Delivery
1501:10.1016/j.tube.2005.08.009
1265:Mashaghi, S.; Jadidi, T.;
838:Elucidation of intestinal
808:chemical conjugate systems
480:(e.g. glycerol bahenate),
400:pharmaceutical formulation
396:nanoparticle drug delivery
29:
27:Novel drug delivery system
2250:
2222:
2201:Scanning probe microscopy
2199:
2176:
2143:
2098:
2061:
2028:
1980:solid lipid nanoparticle
1705:Lasic, Danilo D. (1997).
571:lipid (for stability), a
552:discuss these in detail.
2224:Molecular nanotechnology
2168:Solid lipid nanoparticle
2153:Self-assembled monolayer
961:Nanocarrier Technologies
311:Nanocrystalline material
287:Nanostructured materials
2209:Atomic force microscope
2158:Supramolecular assembly
2145:Molecular self-assembly
797:Alnylam Pharmaceuticals
646:polymeric nanoparticles
563:(the virus that causes
1367:10.1002/advs.202102451
1210:10.1002/adfm.202106727
1137:Manzunath et al., 2005
917:Targeted drug delivery
89:
57:
2298:Technology portal
1676:Byk, Gerardo (2002).
1203:(8). Wiley: 2106727.
789:small interfering RNA
638:drug delivery systems
575:(for structure), and
486:glycerol monostearate
454:core matrix that can
341:Technology portal
136:Mechanical properties
63:
43:
2085:Green nanotechnology
1317:10.3390/nano10040787
1078:10.1038/nrd.2017.243
793:Acuitas Therapeutics
390:. They are a novel
306:Nanoporous materials
169:Buckminsterfullerene
2232:Molecular assembler
895:, the general field
538:sodium taurocholate
380:Lipid nanoparticles
208:Carbon quantum dots
2286:Science portal
2163:DNA nanotechnology
1977:has a profile for
963:. pp. 41–50.
780:and end up inside
671:hot-homogenization
620:delivery systems,
512:). All classes of
329:Science portal
141:Optical properties
90:
58:
18:Lipid nanoparticle
2306:
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1983:
1745:Molecular Therapy
978:978-1-4020-5040-4
610:clinical medicine
412:COVID-19 vaccines
377:
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189:Carbon allotropes
16:(Redirected from
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2242:Mechanosynthesis
2133:characterization
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858:is achieved via
854:. This enhanced
688:intestinal acids
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278:Titanium dioxide
117:Carbon nanotubes
111:
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750:electric charge
742:
734:bioavailability
660:
655:ferrous sulfate
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438:Characteristics
398:), and a novel
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2022:Nanotechnology
2018:
2017:
2010:
2003:
1995:
1973:
1966:
1965:
1964:
1962:
1961:External links
1959:
1958:
1957:
1931:(7): 877–885.
1919:
1893:(4): 475–485.
1881:
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626:microemulsions
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530:sphingomyelins
482:monoglycerides
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2128:Nanoparticles
2126:
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2044:
2043:Organizations
2041:
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2023:
2016:
2011:
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1796:Vancouver Sun
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1575:Drug Delivery
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623:
617:
615:
611:
607:
606:nanoparticles
597:
593:
590:
580:
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555:LNPs used in
553:
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470:triglycerides
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296:Nanocomposite
294:
293:
292:
291:
288:
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274:
271:
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266:
264:
261:
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258:Iron–platinum
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244:
241:
239:
236:
234:
231:
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209:
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204:
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200:
199:nanoparticles
196:
195:
190:
187:
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184:Health impact
182:
180:
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175:
174:C70 fullerene
172:
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2167:
2075:Nanomedicine
2067:applications
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1635:
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1489:Tuberculosis
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1037:
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873:nanoparticle
864:nanoparticle
852:nanoparticle
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663:stearic acid
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600:Applications
594:
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573:phospholipid
554:
549:
546:cytotoxicity
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494:stearic acid
478:diglycerides
441:
386:composed of
379:
378:
262:
233:Cobalt oxide
213:Quantum dots
146:Applications
74:Gene therapy
70:DNA vaccines
1407:Int J Pharm
1128:Small, 1986
942:, uses LNPs
928:, uses LNPs
881:endocytosis
877:endocytosis
730:intravenous
707:hydrophilic
577:cholesterol
514:emulsifiers
502:cholesterol
490:fatty acids
466:surfactants
416:RNA vaccine
382:(LNPs) are
82:antibiotics
50:RNA vaccine
36:DNA vaccine
32:RNA vaccine
2313:Categories
2121:Non-carbon
2112:Nanotubes
2108:Fullerenes
2090:Regulation
1982:(Q7557912)
1724:11 January
1642:11 January
1310:(4): 787.
1045:3 December
947:References
711:lipophilic
667:Carvedilol
561:SARS-CoV-2
534:bile salts
474:tristearin
459:lipophilic
456:solubilize
448:nanometers
253:Iron oxide
160:Fullerenes
54:antibodies
30:See also:
1534:: 18–26.
1219:244085785
922:mRNA-1273
875:could be
860:lymphatic
840:lymphatic
801:patisiran
782:endosomes
758:transfect
715:autoclave
675:compritol
622:liposomes
583:Synthesis
569:PEGylated
462:molecules
444:spherical
424:PEGylated
414:that use
223:Cellulose
179:Chemistry
131:Chemistry
126:Synthesis
86:cosmetics
65:Liposomes
2261:Category
2030:Overview
1953:40506806
1945:25069593
1915:42174732
1907:23697916
1877:10840199
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1427:24012860
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1336:32325941
1282:in vitro
1176:March 6,
1115:Mehnert
1096:29326426
1014:10802410
936:BioNTech
932:BNT162b2
911:Lipoplex
905:Liposome
887:See also
828:ALC-0315
824:BioNTech
818:, while
762:in vitro
614:research
565:COVID-19
518:particle
498:steroids
430:and the
408:Onpattro
301:Nanofoam
268:Platinum
151:Timeline
78:vitamins
2273:Commons
2053:Outline
2038:History
1975:Scholia
1768:5498813
1376:8728822
1327:7221919
1286:in vivo
1251:July 5,
1087:5906799
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924:, from
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812:Moderna
703:corneal
684:gastric
642:in vivo
542:sterols
540:), and
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2063:Impact
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500:(e.g.
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238:Copper
197:Other
46:modRNA
1949:S2CID
1911:S2CID
1835:S2CID
1601:S2CID
1552:S2CID
1470:S2CID
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1215:S2CID
657:(FeSO
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