--- title: Lipid-based Drug Delivery Development with Cayman – Part 2 description: "The best-known variant of \"lipid-based drug delivery systems\" is the so-called lipid nanoparticle." image: https://resources.biomol.com/hubfs/Imported_Blog_Media/LBDDs_Preview_new-Apr-07-2025-06-33-41-4426-PM.png --- en EN DE [** My account ](https://www.biomol.com/account) ** Service/Help - [Contact](https://www.biomol.com/contact) - [Technical Service](https://www.biomol.com/technical-service) - [FAQ](https://www.biomol.com/faq) - [Shipping Costs](https://www.biomol.com/shipping-costs) - [Product Search Tips](https://www.biomol.com/product-search-tips) - [Distributors](https://www.biomol.com/distributors) - [Company History](https://www.biomol.com/company-history) - Cookie Settings - [** Menu ](https://resources.biomol.com/biomol-blog/lipid-based-drug-delivery-development-with-cayman-part-2#offcanvas--left) - [**Search Tips ](https://www.biomol.com/product-search-tips) - [** Search ](https://resources.biomol.com/biomol-blog/lipid-based-drug-delivery-development-with-cayman-part-2#show-hide--search) ** Search   - 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[ learn more ](https://www.biomol.com/resources/) [** To category Products ](https://www.biomol.com/products/) ** - [Company History](https://www.biomol.com/company-history) - [Awards](https://www.biomol.com/awards) - [Contact](https://www.biomol.com/contact-form) - [Technical Support](https://www.biomol.com/technical-service) - [Career](https://www.biomol.com/job-offers) - [FAQ](https://support.biomol.com/?hsLang=en)   - [ Close menu ** ](https://resources.biomol.com/biomol-blog/lipid-based-drug-delivery-development-with-cayman-part-2#close-categories-menu) en DE Categories - [Products](https://www.biomol.com/products/) - [Suppliers](https://www.biomol.com/suppliers/) - [Resources](https://www.biomol.com/resources/) - [Promotions](https://www.biomol.com/promotions/) - [About Biomol](https://www.biomol.com/about-biomol/) Information - [Contact](https://www.biomol.com/contact) - [Technical Service](https://www.biomol.com/technical-service) - [FAQ](https://www.biomol.com/faq) - [Shipping Costs](https://www.biomol.com/shipping-costs) - [Product Search Tips](https://www.biomol.com/product-search-tips) - [Distributors](https://www.biomol.com/distributors) - [Company History](https://www.biomol.com/company-history) - Cookie Settings - [Home](https://www.biomol.com/) - [Blog](https://resources.biomol.com/biomol-blog) - Lipid-based Drug Delivery Development with Cayman – Part 2 - [Lipid Nanoparticle](https://resources.biomol.com/biomol-blog/tag/lipid-nanoparticle) - [Science History](https://resources.biomol.com/biomol-blog/tag/science-history) - [Cayman Chemical](https://resources.biomol.com/biomol-blog/tag/cayman-chemical) - [mRNA](https://resources.biomol.com/biomol-blog/tag/mrna) - [Lipids](https://resources.biomol.com/biomol-blog/tag/lipids) - [Coronavirus](https://resources.biomol.com/biomol-blog/tag/coronavirus) - [Virus](https://resources.biomol.com/biomol-blog/tag/virus) # Lipid-based Drug Delivery Development with Cayman – Part 2 Written by: Dr. Jan Stäcker 08-23-2022 Share post on social media: [Share on Whatsapp ](whatsapp://send?text=https://resources.biomol.com/biomol-blog/lipid-based-drug-delivery-development-with-cayman-part-2) [Share on X ](https://twitter.com/intent/tweet?source=https://resources.biomol.com/biomol-blog/lipid-based-drug-delivery-development-with-cayman-part-2&text=Lipid-based%20Drug%20Delivery%20Development%20with%20Cayman%20–%20Part%202%20-%20https://resources.biomol.com/biomol-blog/lipid-based-drug-delivery-development-with-cayman-part-2) [Share on LinkedIn ](https://www.linkedin.com/shareArticle?mini=true&url=https://resources.biomol.com/biomol-blog/lipid-based-drug-delivery-development-with-cayman-part-2) [Share on Facebook ](https://www.facebook.com/sharer/sharer.php?u=https://resources.biomol.com/biomol-blog/lipid-based-drug-delivery-development-with-cayman-part-2) ![Lipid-based Drug Delivery Development with Cayman – Part 2](https://resources.biomol.com/hubfs/Imported_Blog_Media/LBDDs_Preview_new-Apr-07-2025-06-33-41-4426-PM.png) The best-known variant of "lipid-based drug delivery systems" (LBDDS) is the so-called lipid nanoparticle (LNP). As already mentioned in [the first part of our small series on LBDDS](https://resources.biomol.com/biomol-blog/lipid-based-drug-delivery-development-with-cayman-part-1?hsLang=en), LNPs are mainly used for the packaging and delivery of mRNA-based drugs. In order for mRNA drugs to reach their target site in a stable and safe manner, they need to be packaged in such a way that, on the one hand, they are protected from degradation by abundant RNases and, on the other hand, they are allowed to be taken up into the target cells. These are exactly the properties offered by LNPs! In the second part of our LBDDS blog series, we will first provide an overview of the developmental history of LNPs and the "endosomal escape" – a crucial point in the transport pathway of LNPs. We will then go into the potential medical applications of LNPs – all the way to SARS-CoV-2 vaccination! ### These topics await you: [1) A Look at History: The Development of Lipid Nanoparticle](https://resources.biomol.com/biomol-blog/lipid-based-drug-delivery-development-with-cayman-part-2#1)[s](https://resources.biomol.com/biomol-blog/lipid-based-drug-delivery-development-with-cayman-part-2#1) [2) Arrived in the Target Cell: Now what?](https://resources.biomol.com/biomol-blog/lipid-based-drug-delivery-development-with-cayman-part-2#2) [3) Possible Applications of Lipid Nanoparticles](https://resources.biomol.com/biomol-blog/lipid-based-drug-delivery-development-with-cayman-part-2#3) [![Subscribe to the free Biomol newsletter and never miss a blog article again!](https://hubspot-no-cache-eu1-prod.s3.amazonaws.com/cta/default/144662462/80065e88-f5aa-4618-9cde-43189a3045f3.png)](https://hubspot-cta-redirect-eu1-prod.s3.amazonaws.com/cta/redirect/144662462/80065e88-f5aa-4618-9cde-43189a3045f3)   ## **A Look at History: The Development of Lipid Nanoparticles** LNPs gained widespread recognition as a result of the COVID-19 pandemic. In fact, research on LNPs and their potential applications has been ongoing for nearly 4 decades, and the success of mRNA-based COVID-19 vaccines would not have been possible without these years of research (Fig. 1). The first milestone on the road to mRNA-based vaccines was the discovery of mRNA and its function in 1961 [1]. At that time, probably no one thought of its possible use in vaccines. Almost 30 years later, in 1989, the first cationic LNP-mRNA formulations were developed [2], followed four more years later by the development of liposome-mRNA formulations for use as influenza vaccines [3]. ![LNP-History_EN](https://resources.biomol.com/hubfs/Imported_Blog_Media/LNP-History_EN-1.png) *Figure 1: Timeline of some mRNA and LNP research milestones.** COVID-19, coronavirus disease 2019; EMA, European Medicines Agency; FDA, United States Food and Drug Administration; LNP, Lipid-Nanopartikel. Modified from [4]. * Since the mid-90s, various LNPs encapsulating for example amphotericin B or vincristine, have been produced and approved by the FDA (U.S. Food and Drug Administration) [5]. In parallel, numerous clinical trials were conducted testing the use of LNP-mRNA formulations against different diseases such as cancer or influenza (Fig. 1). These naturally include clinical trials on COVID-19 vaccines, and in 2020, the two COVID-19 vaccines "mRNA-1273" and "BNT162b" received regulatory approval from authorities in several countries. Another recent milestone is the development and approval of the LNP-based drug "Onpattro" [5]. In this drug, the LNPs encapsulate so-called siRNA (small interfering RNA), which is intended to treat diseases via RNA interference ("gene silencing"). "Onpattro" thus represents the first approved representative of this new class of drugs. ## **Arrived in the Target Cell: Now what?** For mRNA-based drugs to produce their therapeutic effects, the LNPs encapsulating the mRNA must reach the corresponding target cells unharmed [6, 7]. In addition, sufficient protein material must be generated from the mRNA to achieve the desired effect. A critical step in the path of LNPs is the so-called "endosomal escape" (Fig. 2). After the LNPs (with the contained mRNA) reached the target tissue, they must enter the target cells, which can occur via various endocytotic processes. After internalization by the target cell, the LNPs are in the endosome, from which they must "escape" (hence "endosomal escape"). Only after this step the mRNA is released, allowing it to be present in the cytoplasm of the cell and translated into protein (Fig. 2) [6, 7].  ![Endosomal_Escape_ENY3HllrYuD8H7Z](https://resources.biomol.com/hubfs/Imported_Blog_Media/Endosomal_Escape_ENY3HllrYuD8H7Z-1.png) *Figure 2: Schematic representation of the "endosomal escape"**. After internalization of the LNP with the encapsulated mRNA, the LNP is located in the endosome. The endosomal escape frees the LNP and releases the mRNA into the cytoplasm. The mRNA is then translated into protein (transmembrane, secretory or intracellular). Modified from [4].* This step is of great importance, however, only a small fraction of LNPs actually manages endosomal escape [8]. The mechanism is not yet fully understood. It is believed that the electrostatic interaction of positively charged lipids of LNPs with the negatively charged endosomal membrane causes mRNA molecules to gradually enter the cytoplasm [6, 7]. Therefore, the composition and nature of lipids may influence endosomal escape. [![Came to stay? Follow us on LinkedIn!](https://hubspot-no-cache-eu1-prod.s3.amazonaws.com/cta/default/144662462/efba0793-3cce-47e7-bc4a-e5b491931931.png)](https://hubspot-cta-redirect-eu1-prod.s3.amazonaws.com/cta/redirect/144662462/efba0793-3cce-47e7-bc4a-e5b491931931) ## **Possible Applications of Lipid Nanoparticles** The properties and potential applications of LNPs have been investigated in numerous clinical and preclinical studies over the past decades. This was among the reasons for the rapid development and application of LNP-mRNA-based COVID-19 vaccines. For example, mRNA-1273 was produced just one month after the genome sequence of SARS-CoV-2 became available [9, 10]. However, COVID-19 vaccines are only one example of many where LNP-mRNA formulations are (to be) applied to prevent infectious diseases. The unique properties of LNP and mRNA make them ideally suited for use in vaccines. mRNA is non-infectious, cannot integrate into the genome, and can code for a wide range of antigens [9-11]. Moreover, multiple mRNAs encoding different antigens can be combined in one LNP. Due to their short production time, LNP-mRNA-based vaccines are predestined for use against emerging pathogens. In addition to their use in the COVID-19 pandemic, LNP-mRNA formulations are also being tested for influenza, Zika, Rabies, and Ebola virus vaccines, among others [see 4]. In addition, studies also suggest potential use in bacterial [12] and parasitic [13] infections. LNP-mRNA-based vaccines could also help combat various cancers, and numerous candidates are currently being investigated in clinical trials [see 4]. These include, for example, vaccines against melanoma or gastrointestinal cancer. One approach is the use of so-called "neoantigens". These are usually tumor-specific and exhibit high immunogenicity. Furthermore, they are often different between individual patients [7, 11]. These characteristics allow the development of personalized vaccines. Many such personalized cancer vaccines based on LNP-mRNA formulations are currently in clinical trials. Another area of application for LNP-mRNA vaccines is genetic diseases. Here, the focus is currently on inherited metabolism disorders in which a key enzyme cannot perform its function correctly or at all due to a mutation. This leads to the accumulation of certain metabolites, which in the worst case can lead to death [14]. One way to treat such diseases is the supplement of therapeutic proteins, which, however, does not provide a long-term cure. Alternatively, LNP-mRNA-based protein replacement therapies are being tested [14]. These have the advantage that the mRNA can be translated into the desired protein (whether secretory, intracellular or transmembrane) within the patient. As a result, the protein exhibits the same post-translational modifications that the protein being replaced would have.     History shows that mRNA and LNPs are promising tools for use in the field of vaccine research and the control of various diseases. Not least, the SARS-CoV-2 pandemic proved the importance of constant work on such new techniques. And the recent development of the LNP-siRNA formulation suggests that the potential of lipid-based drug delivery systems is far from exhausted. Want to work on LBDDS yourself? Check out the related products from our partner [Cayman Chemical](https://www.biomol.com/cayman/).  You can also learn more about LBDD systems, the cargoes they carry, and the basic concepts and procedures for preparing LNPs in Cayman's [Guide to Lipid Nanoparticle Formulation](https://www.biomol.com/resources/catalogs/cayman-chemical/).     ## Sources [1] Cobb, M. Who discovered messenger RNA? Curr. Biol. 25, R526–R532 (2015) [2] Malone, R. W., Felgner, P. L. & Verma, I. M. Cationic liposome- mediated RNA transfection. Proc. Natl Acad. Sci. USA 86, 6077–6081 (1989). [3] Martinon, F. et al. Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome- entrapped mRNA. Eur. J. Immunol. 23, 1719–1722 (1993). [4] Hou, X. et al. Lipid nanoparticles for mRNA delivery. Nat. Rev. Mater. 6, 1078–1094 (2021). [5] Akinc, A. et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat. Nanotechnol. 14, 1084–1087 (2019). [6] Hajj, K. A. & Whitehead, K. A. Tools for translation: non- viral materials for therapeutic mRNA delivery. Nat. Rev. Mater. 2, 17056 (2017). [7] Kowalski, P. S., Rudra, A., Miao, L. & Anderson, D. G. Delivering the messenger: advances in technologies for therapeutic mRNA delivery. Mol. Ther. 27, 710–728 (2019). [8] Gilleron, J. et al. Image- based analysis of lipid nanoparticle–mediated siRNA delivery, intracellular trafficking and endosomal escape. Nat. Biotechnol. 31, 638–646 (2013). [9] Gebre, M. S. et al. Novel approaches for vaccine development. Cell 184, 1589–1603 (2021). [10] Kim, J., Eygeris, Y., Gupta, M. & Sahay, G. Self- assembled mRNA vaccines. Adv. Drug Deliv. Rev. 170, 83–112 (2021). [11] Pardi, N., Hogan, M. J., Porter, F. W. & Weissman, D. mRNA vaccines — a new era in vaccinology. Nat. Rev. Drug Discov. 17, 261–279 (2018). [12] Maruggi, G. et al. Immunogenicity and protective efficacy induced by self- amplifying mRNA vaccines encoding bacterial antigens. Vaccine 35, 361–368 (2017). [13] Garcia, A. B. et al. Neutralization of the Plasmodiumencoded MIF ortholog confers protective immunity against malaria infection. Nat. Commun. 9, 2714 (2018). [14] Zhao, W., Hou, X., Vick, O. G. & Dong, Y. RNA delivery biomaterials for the treatment of genetic and rare diseases. Biomaterials 217, 119291 (2019). ---   ## You might also like... SEE MORE BLOGPOST ![Lipid-based Drug Delivery Development with Cayman – Part 1](https://resources.biomol.com/hs-fs/hubfs/Imported_Blog_Media/LBDDs_Preview_new-Apr-07-2025-06-33-41-4426-PM.png?width=600&name=LBDDs_Preview_new-Apr-07-2025-06-33-41-4426-PM.png) ##### Lipid-based Drug Delivery Development with Cayman – Part 1 Lipid-based drug delivery systems (LBDDS) have been studied and developed since the 1960s. The main objective is to develop formulations... - [Lipid Nanoparticle](https://resources.biomol.com/biomol-blog/tag/lipid-nanoparticle) - [Cayman Chemical](https://resources.biomol.com/biomol-blog/tag/cayman-chemical) - [Lipids](https://resources.biomol.com/biomol-blog/tag/lipids) - [Coronavirus](https://resources.biomol.com/biomol-blog/tag/coronavirus) - [Virus](https://resources.biomol.com/biomol-blog/tag/virus) ![LNPs Beyond mRNA Vaccines – Where Do We Go from Here?](https://resources.biomol.com/hs-fs/hubfs/Imported_Blog_Media/Cayman_LNPs_Preview-2.png?width=600&name=Cayman_LNPs_Preview-2.png) ##### LNPs Beyond mRNA Vaccines – Where Do We Go from Here? Lipid nanoparticles (LNPs) are primed to revolutionize modern medicine. 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