--- title: Lung‑Targeted tLNPs with PEG‑Free Shielding and CliCr® Conjugation description: Discover how lung‑targeted tLNPs using PEG‑free PSar shielding and CliCr® ligand conjugation enable selective pulmonary delivery. image: https://resources.curapath.com/hubfs/Captura%20de%20pantalla%202026-06-25%20104706-1.png --- [![White](https://resources.curapath.com/hs-fs/hubfs/White.png?width=1063&height=400&name=White.png "White")](https://curapath.com/) Resources # Lung-Targeted LNP Development (Case Study)  Explore how next‑generation **lung‑targeted LNPs** leverage **PEG‑free PSar shielding** and **CliCr® conjugation** to enable efficient ligand attachment, overcome liver tropism, and achieve selective pulmonary delivery with minimal impact on core LNP properties.  [Back to resources](https://resources.curapath.com/en/curapath-resource-library?hsLang=en) ## Lung‑Targeted LNP Development ### Executive Summary Developing targeted lipid nanoparticles requires more than selecting a formulation strategy. Sponsors must evaluate how targeting ligands, shielding lipids, conjugation chemistry, and manufacturing workflows work together to improve tissue selectivity while maintaining LNP quality attributes. This case study presents Curapath’s approach to **lung-targeted LNP development**, combining **PEG-free shielding lipids** with **CliCr® conjugation technology** to enable the attachment of targeting ligands directly onto formulated LNPs. The study highlights how peptide-functionalized LNPs can modulate biodistribution, enhance tissue-selective delivery, and support the development of more precise RNA delivery systems. Download the case study to explore how Curapath’s targeted LNP platform can support advanced delivery strategies for hard-to-reach tissues.  ### Key Takeaways - A practical example of [active targeting applied to LNP development](https://resources.curapath.com/active-targeting-solutions?hsLang=en) - How [PEG-free shielding lipids](https://resources.curapath.com/peg-alternatives-for-lnps?hsLang=en) can be combined with CliCr® conjugation technology - [Characterization](https://resources.curapath.com/en/lnp-analytical.methods?hsLang=en) data showing comparable LNP profiles after functionalization - In vitro and in vivo results supporting lung-targeted transfection - Key advantages of a customizable targeted LNP platform for RNA delivery ### About This Case Study  Active targeting is becoming an increasingly important strategy in lipid nanoparticle development, particularly for programs aiming to move beyond liver-dominant delivery. By functionalizing nanoparticles with specific targeting ligands, LNPs can be designed to interact more selectively with target cells through receptor-mediated mechanisms. This case study explores Curapath’s development workflow for **targeted LNPs**, using a **CliCr®-modified PEG-free shielding lipid** designed to enable ligand conjugation after LNP formulation. The approach allows the attachment of targeting ligands such as peptides or antibodies directly onto formulated LNPs, supporting a flexible and customizable strategy for tissue-selective delivery. In the study, different LNP formulations were evaluated, including a non-functionalized stealth LNP and an RGD-functionalized LNP. Characterization results showed that functionalization maintained a comparable LNP profile, with both non-functionalized and RGD-functionalized LNPs achieving high encapsulation efficiency. In vitro and in vivo assays further demonstrated how peptide functionalization can increase transfection efficiency and improve lung-selective biodistribution  By combining PEG-free shielding lipid design, click-based conjugation, and targeted formulation development, Curapath provides a ready-to-use platform for sponsors developing next-generation RNA delivery systems for challenging tissues such as the lung, T cells, and the CNS.  ### Who Should Read This Case Study?  - Biotech and pharma teams developing targeted RNA delivery systems  - Companies working on extrahepatic LNP delivery  - CMC and formulation teams evaluating ligand-functionalized LNPs  - Researchers exploring PEG-free shielding strategies for LNPs - Sponsors looking for customizable LNP platforms with GMP production potential  - Business development and technical teams assessing partners for advanced nanoparticle development      Form ## Download the Lung-Targeted LNP Development (Case Study) ![Captura de pantalla 2026-06-25 104706](https://resources.curapath.com/hs-fs/hubfs/Captura%20de%20pantalla%202026-06-25%20104706.png?width=663&height=863&name=Captura%20de%20pantalla%202026-06-25%20104706.png) Related Resources ## Explore additional Curapath resources covering advanced drug delivery systems, analytical characterization, and nanoparticle development.  Discover technical insights, application notes, and scientific content designed to support **RNA therapeutics, lipid nanoparticles, and polymer-based delivery platforms.**  - [PEG Free shielding lipids](https://resources.curapath.com/tlnp-development-lung-case-study#item1-module_17766725744085) - [Products](https://resources.curapath.com/tlnp-development-lung-case-study#item2-module_17766725744085) - [Formulation Development Services](https://resources.curapath.com/tlnp-development-lung-case-study#item3-module_17766725744085) - [Active targeting](https://resources.curapath.com/tlnp-development-lung-case-study#item4-module_17766725744085) - [Services](https://resources.curapath.com/tlnp-development-lung-case-study#item5-module_17766725744085) - [Blog post](https://resources.curapath.com/tlnp-development-lung-case-study#item6-module_17766725744085) PEG Alternatives ## PEG Free shielding lipids ****Access the full highlight to discover our next‑generation PEG‑free shielding lipid technology that improve formulation flexibility, in vivo performance, and compatibility with advanced RNA therapeutics.****   [GET STARTED](https://resources.curapath.com/peg-alternatives-for-lnps?hsLang=en) ![PEG- Free Shielding Lipids 2026-1](https://resources.curapath.com/hs-fs/hubfs/PEG-%20Free%20Shielding%20Lipids%202026-1.jpg?width=500&height=706&name=PEG-%20Free%20Shielding%20Lipids%202026-1.jpg) Products ## Curapath Product Catalog Discover Curapath's cutting-edge offerings in our catalog. Explore our LNP and PNP components, as well as our polymer conjugates, all designed to advance drug delivery. Enhance your research and development with our high-quality products.  [Donwload](https://resources.curapath.com/en/curapath-product-catalog?hsLang=en) ![_2025 Product catalog CURAPATH-v2511](https://resources.curapath.com/hs-fs/hubfs/_2025%20%20Product%20catalog%20CURAPATH-v2511.png?width=500&height=707&name=_2025%20%20Product%20catalog%20CURAPATH-v2511.png) Formulation Screening ## Formulation Development Services  Discover Curapath’s Essential, Advanced, and Expert formulation packages for LNP & PNP systems, flexible, cost-effective solutions for drug delivery development.  [Donwload](https://resources.curapath.com/en/curapath-formulations-development-packages-2026?hsLang=en) ![Formulation Development Services MA (1)](https://resources.curapath.com/hs-fs/hubfs/Formulation%20Development%20Services%20%20MA%20(1).png?width=500&height=707&name=Formulation%20Development%20Services%20%20MA%20(1).png) solutions for Active Targeting ## solutions for Active Targeting  ****Access the full highlight to discover how integrated active‑targeting solutions, combining advanced ligand conjugation, PEG‑free shielding systems, and optimized LNP architecture, expand formulation versatility, strengthen extrahepatic delivery, and support the next generation of RNA and gene‑therapy platforms.****   [Download](https://resources.curapath.com/active-targeting-solutions?hsLang=en) ![Solutions for Active Targeting (1).pptx](https://resources.curapath.com/hs-fs/hubfs/Solutions%20for%20Active%20Targeting%20(1).pptx.png?width=500&height=708&name=Solutions%20for%20Active%20Targeting%20(1).pptx.png) CDMO ## CDMO Services Brochure This leaflet outlines Curapath’s lipid- and polymer-based CDMO platform for advanced drug delivery, covering drug substance and drug product development, analytical services, GMP manufacturing, and sterile Fill & Finish capabilities.     [GET STARTED](https://resources.curapath.com/cdmo-services-brochure?hsLang=en) ![Def Curapath CDMO-3.pdf](https://resources.curapath.com/hs-fs/hubfs/Def%20Curapath%20CDMO-3.pdf.jpg?width=500&height=707&name=Def%20Curapath%20CDMO-3.pdf.jpg) Active Targeting ## Active Targeting in LNPs: Why Surface Functionalization Matters Explore how **surface functionalization** drives the **targeting** efficiency and biological performance of lipid nanoparticles. Ligand density, orientation, and linker stability shape receptor engagement, cellular uptake, and the ability to reach extrahepatic tissues while preserving nanoparticle integrity. The article also contrasts traditional chemistries with advanced platforms like **CliCr®**, which improve reaction speed, solubility, and reduce aggregation. These modular strategies, using pre‑functionalized lipids or post‑formulation conjugation, enable more precise, scalable, and clinically adaptable LNP systems for targeted RNA delivery.     [Read Article](https://blog.curapath.com/active-targeting-in-lnps-why-surface-functionalization-matters?hsLang=en) ![fotos blog](https://resources.curapath.com/hs-fs/hubfs/fotos%20blog.jpg?width=1920&height=1080&name=fotos%20blog.jpg) Lung-Targeted LNP Development ## Frequently asked Questions ##### [Lung-Targeted LNP What are targeted lipid nanoparticles?](https://resources.curapath.com/tlnp-development-lung-case-study#collapse1-module_17766725844145) Targeted lipid nanoparticles, or targeted LNPs, are lipid-based delivery systems designed to improve selective interaction with specific cells or tissues. This is typically achieved by functionalizing the nanoparticle surface with targeting ligands such as peptides, antibodies, or small molecules that recognize receptors or markers expressed on target cells.  ##### [Lung-Targeted LNP How does active targeting improve LNP delivery?](https://resources.curapath.com/tlnp-development-lung-case-study#collapse2-module_17766725844145) Active targeting can help improve delivery specificity by enabling LNPs to interact more selectively with target cells. By adding ligands to the nanoparticle surface, targeted LNPs may enhance cellular uptake, modulate biodistribution, and reduce unwanted exposure in non-target tissues.    ##### [Lung-Targeted LNP What is lung-targeted LNP development?](https://resources.curapath.com/tlnp-development-lung-case-study#collapse3-module_17766725844145) Lung-targeted LNP development focuses on designing lipid nanoparticles that can improve delivery toward lung tissue. This requires optimization of formulation composition, shielding strategy, ligand selection, conjugation chemistry, and analytical characterization to support tissue-selective RNA delivery. ##### [Lung-Targeted LNP What role do PEG-free shielding lipids play in targeted LNPs?](https://resources.curapath.com/tlnp-development-lung-case-study#collapse4-module_17766725844145) PEG-free shielding lipids can help modulate the surface properties of LNPs while avoiding some of the limitations associated with PEG-based systems. In targeted LNP development, PEG-free shielding lipids can also be engineered with functional groups that enable ligand attachment and support active targeting strategies.    ##### [Lung-Targeted LNP What is CliCr® conjugation technology?](https://resources.curapath.com/tlnp-development-lung-case-study#collapse5-module_17766725844145) CliCr® is a conjugation technology used to enable the attachment of targeting ligands to functionalized shielding lipids. In the context of targeted LNP development, CliCr®-modified shielding lipids can allow ligands such as peptides or antibodies to be attached directly onto formulated LNPs.  ##### [Lung-Targeted LNP Can targeting ligands be attached after LNP formulation?](https://resources.curapath.com/tlnp-development-lung-case-study#collapse6-module_17766725844145) Yes. One advantage of using functionalized shielding lipids and conjugation chemistry is the possibility of attaching selected targeting ligands after LNP formulation. This can provide flexibility during development and may simplify the evaluation of different ligands without fully redesigning the core LNP formulation each time. ##### [Lung-Targeted LNP What should sponsors consider when developing targeted LNPs?](https://resources.curapath.com/tlnp-development-lung-case-study#collapse7-module_17766725844145) Sponsors should evaluate the target biology, ligand-receptor interaction, shielding lipid design, conjugation chemistry, formulation robustness, analytical characterization, scalability, and regulatory expectations. A successful targeted LNP program requires integration of formulation science, bioassays, CMC strategy, and manufacturability from early development onward.  [Contact](https://curapath.com/contact-us/) ![Lipid-Nanopeptide_0](https://resources.curapath.com/hs-fs/hubfs/Lipid-Nanopeptide_0.png?width=500&height=500&name=Lipid-Nanopeptide_0.png) Support for Your Therapeutic Program ### Contact a Chemist Today Contact Us, and we can discuss your specific therapeutic program and how Curapath can help build the right solution to advance your unique drug. 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