Engineered strategies for enhancing mRNA vaccine stability in delivery and storage

Elif Naz Cerav, Zhiying Yao and Bingbing Sun

Nanoscale, 2026, 18, 5667
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Lipid Nanoparticle Encapsulation Empowers Poly(I:C) to Activate Cytoplasmic RLRs and Thereby Increases Its Adjuvanticity

Alexander Lamoot, Sonia Jangra, Gabriel Laghlali, Prajakta Warang, Gagandeep Singh, Lauren A. Chang, Seok‐Chan Park, Gagandeep Singh, Kim De Swarte, Zifu Zhong, Benoit Louage, Emily De Lombaerde, Tingting Ye, Yong Chen, Sara Cuadrado‐Castano, Stefan Lienenklaus, Niek N. Sanders, Bart N. Lambrecht, Adolfo García‐Sastre, Michael Schotsaert and Bruno G. De Geest

Small, 2024, 20
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Quality-by-Design (QbD) optimization of lyophilization parameters for siRNA-loaded LNPs using sequential Design of Experiments (DoE)

Manon Degey, Laura Meloni, Berfin Dede, Inês Guerreiro, Noémie Penoy, Pierre-Yves Sacré, Manon Berger, Louise Conrard, Erika Hendrickx, Erik Maquoi, Jeanne Leblond Chain, Brigitte Evrard and Géraldine Piel

International Journal of Pharmaceutics, 2026, 127032
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Emerging lipid nanoparticle systems capable of efficient intramuscular RNA delivery

Aun Raza, Runtong Zhang, Ruonan Lu, Jingyuan Wen and Wei Wu

Nanomedicine, 2025, 20, 2545
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Lyophilized monkeypox mRNA lipid nanoparticle vaccines with long-term stability and robust immune responses in mice

Bin Wang, Quanyi Yin, Li Yi, Caixia Su, Yang Wen, Man Qiao, Yingchen Ju, Zhihua Liu, Yelin Xiong and Zhilei Liu

Human Vaccines & Immunotherapeutics, 2025, 21
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Cryoprotectant optimization for enhanced stability and transfection efficiency of pDNA-loaded ionizable lipid nanoparticles

Heloísa Athaydes Seabra Ferreira, Sérgio Ricardo Aluotto Scalzo Júnior, Kevin Kelton Santos de Faria, Gabriel Henrique Costa Silva, Marco Túllio Rodrigues Alves, Anderson Oliveira Lobo and Pedro Pires Goulart Guimarães

International Journal of Pharmaceutics, 2024, 665, 124696
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Endothelium-targeted NF-κB siRNA nanogel for magnetic resonance imaging and visualized-anti-inflammation treatment of atherosclerosis

Yuanyuan Guo, Fujun Wang, Sunli Wan, Xinhua Liu, Yu Huang, Miao Xie, Xiaoer Wei, Wangshu Zhu, Tingting Yao, Yuehua Li, Chuan Zhang and Yueqi Zhu

Biomaterials, 2025, 314, 122897
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Overcoming cold chain challenges: Cryoprotection of self-amplifying mRNA polyplexes for long-term storage at ambient temperature

Lisa Opsomer, Somdeb Jana, Richard Hoogenboom and Niek Sanders

Journal of Controlled Release, 2025, 387, 114259
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Not so cold! Improving the thermostability of mRNA vaccines

Jean Haensler, Luc Even, Pierre Wils, Fethi Bensaid, Anusha Dias, Hongfeng Deng, Shrirang Karve and Frank DeRosa

Expert Review of Vaccines, 2025, 24, 1149
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Intratumoral delivery of lipid nanoparticle-formulated mRNA encoding IL-21, IL-7, and 4-1BBL induces systemic anti-tumor immunity

Ahmed E. I. Hamouda, Jessica Filtjens, Elisabeth Brabants, Daliya Kancheva, Ayla Debraekeleer, Jan Brughmans, Lotte Jacobs, Pauline M. R. Bardet, Elisabeth Knetemann, Pierre Lefesvre, Lize Allonsius, Mark Gontsarik, Ismael Varela, Marian Crabbé, Emile J. Clappaert, Federica Cappellesso, Aarushi A. Caro, Alícia Gordún Peiró, Luna Fredericq, Eva Hadadi, Mariona Estapé Senti, Raymond Schiffelers, Leo A. van Grunsven, Frank Aboubakar Nana, Bruno G. De Geest, Sofie Deschoemaeker, Stefaan De Koker, Florence Lambolez and Damya Laoui

Nat Commun, 2024, 15
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A Review on the Stability Challenges of Advanced Biologic Therapeutics

Sruthi Sarvepalli, Shashank Reddy Pasika, Vartika Verma, Anusha Thumma, Sandeep Bolla, Pavan Kumar Nukala, Arun Butreddy and Pradeep Kumar Bolla

Pharmaceutics, 2025, 17, 550
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Drying technologies for messenger RNA and other nucleic acid-lipid nanoparticles: advances in freeze-drying and beyond

Zixuan Zhen, Mittal Darji, Xinhao Lin, Robin H. Bogner and Xiuling Lu

AAPS Open, 2026, 12
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Engineering mRNA-LNP therapeutics: Nanomaterials for preservation, controlled release, and inhalation delivery

Muhammad Imad Khan Khalil, Muhammad Kamran Khan, Muhammad Noman Noor, Jingyu Shi, Imam Hussain, Ijaz Ahmad, Shaukat Aziz, Tong Zhenbo and Hongtao Xu

Next Materials, 2026, 12, 102375
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mRNA vaccine in gastrointestinal tumors: Immunomodulatory effects and immunotherapy

Ao Zhang, Qingming Ji, Xia Sheng and Hui Wu

Biomedicine & Pharmacotherapy, 2023, 166, 115361
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Investigations Into the Influence of Ionizable Lipids on the Stability of Lipid Nanoparticle

Jie Wang, Zhitong Guo, Jun Yang, Haiyin Yang, Shaoping Jiang, Abid Naeem, Bo Hu, Yuhua Weng and Yuanyu Huang

MedComm – Biomaterials and Applications, 2025, 4
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Machine learning-driven optimization of mRNA-lipid nanoparticle vaccine quality with XGBoost/Bayesian method and ensemble model approaches

Ravi Maharjan, Ki Hyun Kim, Kyeong Lee, Hyo-Kyung Han and Seong Hoon Jeong

Journal of Pharmaceutical Analysis, 2024, 14, 100996
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Physicochemical and structural insights into lyophilized mRNA-LNP from lyoprotectant and buffer screenings

Yuchen Fan, Diamanda Rigas, Lee Joon Kim, Feng-Peng Chang, Nanzhi Zang, Kristina McKee, Christopher C. Kemball, Zhixin Yu, Pascal Winkler, Wan-Chih Su, Pierce Jessen, Greg L. Hura, Tao Chen, Stefan G. Koenig, Karthik Nagapudi, Dennis Leung and Chun-Wan Yen

Journal of Controlled Release, 2024, 373, 727
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Delivery of small interfering RNA through lyophilized natural lipid nanoparticles: effects of natural lipid selection

Hangjie Wang, Wei Li, Junyan Chen, Rong Chen, Yuwei Qi, Linshuang Shen, Kaidi Chen, Lewei Dai, Yuxin Sheng, An Wang, Hong Wang, Chujian Chen, Xiao Cheng and Mancang Gu

Pharmaceutical Biology, 2025, 63, 343
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Targeted Delivery of mRNA with Polymer–Lipid Nanoparticles for In Vivo Base Editing

Qimingxing Chen, Yan Chang, Xiaoyan He, Yan Ding, Runyuan Wang, Ran Luo, Jialu Yuan, Jiabei Chen, Guisheng Zhong, Huiying Yang, Jia Chen and Jianfeng Li

ACS Nano, 2025, 19, 7835
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Freezing-Induced Stress in mRNA-Lipid Nanoparticles During Lyophilization: Mechanistic Insights From Process and Formulation Studies

Anna Ruppl, Andrei Hutanu, Monika Köll-Weber and Andrea Allmendinger

Pharm Res, 2026, 43, 877
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Freeze-Drying of mRNA-LNPs Vaccines: A Review

MD Faizul Hussain Khan, Floriane Baudin, Ayyappasamy Sudalaiyadum Perumal and Amine A. Kamen

Vaccines, 2025, 13, 853
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Development of an Alcohol Dilution–Lyophilization Method for the Preparation of mRNA-LNPs with Improved Storage Stability

Daiki Shirane, Hiroki Tanaka, Yu Sakurai, Sakura Taneichi, Yuta Nakai, Kota Tange, Itsuko Ishii and Hidetaka Akita

Pharmaceutics, 2023, 15, 1819
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Advances in stabilizing lipid-based nanoparticles: The central role of lyophilization

Irene Bautista-Lopez, Markel Lafuente-Merchan, Idoia Gallego, Lucia Enriquez-Rodriguez, Iván Maldonado, Murugan Ramalingam, Gustavo Puras and José Luis Pedraz

Journal of Controlled Release, 2026, 394, 114888
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A functional lyoprotectant platform enables storage-stable, mucus-penetrating siRNA delivery to the lung

Wenliang Sun, Liangkun Xie, Xiaotong Jiang, Qingyi Zhu, Hu Feng, Dongmei Cun, Lan Wu and Mingshi Yang

Journal of Controlled Release, 2026, 393, 114749
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Lipid nanoparticle–based mRNA platforms for mucosal HIV vaccines: formulation advances, immune mechanisms, and translational pathways

Narinderjit Singh Sawaran Singh, Ibrahim Saeed Gataa, Luma Hussain Saleh, Subbulakshmi Ganesan, V. Kavitha, Laxmidhar Maharana, Renu Sharma, Mutabar Latipova, Nazira Madatova, Doniyor Jumanazarov and Aseel Smerat

Arch Microbiol, 2026, 208
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mRNA vaccine platforms and novel delivery systems: From mechanistic principles to clinical translation

Yunchang Yang, Yunqin Sun, Xinyao Kang and Yaofeng Wang

Human Vaccines & Immunotherapeutics, 2025, 21
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Advancing mRNA vaccines for infectious diseases: key components, innovations, and clinical progress

Sha Li, Lu Zheng, Jingyi Zhong and Xihui Gao

Essays in Biochemistry, 2025, 69, 109
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Spin freeze-drying in continuous biomanufacturing: Boon or mirage?

Teja Kumar Ponduri and G.S.N. Koteswara Rao

Journal of Drug Delivery Science and Technology, 2026, 116, 107909
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Application of Saccharide Cryoprotectants in the Freezing or Lyophilization Process of Lipid Nanoparticles Encapsulating Gene Drugs for Regenerative Medicine

Wanqi Li, Ting Wang, Jianyang Chen, Minmei Guo, Ling Ling and Akon Higuchi

RMD, 2024, 3
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The Impact of COVID-19 on RNA Therapeutics: A Surge in Lipid Nanoparticles and Alternative Delivery Systems

Nargish Parvin, Tapas K. Mandal and Sang-Woo Joo

Pharmaceutics, 2024, 16, 1366
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Oscillation-generating micromixing (FDmiX) – a new method for manufacturing of mRNA-lipid nanoparticles with scalable high-throughput production

Fitore Mejzini, Frank Erdmann, Julian Kunert, Henrike Lucas, Julia Kollan, Stephanie Krüger and Karsten Mäder

Journal of Controlled Release, 2026, 393, 114783
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Lyophilized monoclonal antibody (mAb) encoded mRNA—lipid nanoparticles (LNPs) lead to stable in vivo expression of mAb after room temperature storage

Zimeng Wang, Bei Cheng, Christine Tkaczyk, Michael Newton, Shuolin Cui, Bohdan Andreiuk, Sanjib Saha, Sabrina Khan, Charles Chen, Bin Yang, Adam Gamson, Sarah Siddiqui, George Thom, Antonio DiGiandomenico and Liping Zhou

AAPS Open, 2026, 12
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End-to-end digital twin software for continuous mRNA manufacturing

Mohammed Aatif Shahab, Nathan Merica Stover, Hasan Al-Mahayni, Prakitr Srisuma, Jie Wang, Sunkyu Shin, Anish Dighe, Bernhardt L. Trout, Allan S. Myerson and Richard D. Braatz

International Journal of Pharmaceutics, 2025, 686, 126301
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Revolutionizing mRNA Vaccines Through Innovative Formulation and Delivery Strategies

Munazza Fatima, Timothy An and Kee-Jong Hong

Biomolecules, 2025, 15, 359
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Lyophilized SARS-CoV-2 self-amplifying RNA vaccines for microneedle array patch delivery

Madison M. Driskill, Ian A. Coates, Paul J. Hurst, Netra U. Rajesh, Maria T. Dulay, Robert M. Waymouth, Wataru Akahata, Kenta Matsuda, Jonathan F. Smith, Gunilla B. Jacobson, Jillian L. Perry, Shaomin Tian and Joseph M. DeSimone

Journal of Controlled Release, 2025, 384, 113944
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Thin-film freeze-drying of an influenza virus hemagglutinin mRNA vaccine in unilamellar lipid nanoparticles with blebs

Qin Li, Ruiqi Shi, Haiyue Xu, Khaled AboulFotouh, Molly M.H. Sung, Thomas H. Oguin, Madeline Hayes, Chaeho Moon, Huy M. Dao, Houping Ni, Sawittree Sahakijpijarn, Chris Cano, Gregory J. Davenport, Robert O. Williams, Jon Le Huray, Zhengrong Cui and Drew Weissman

Journal of Controlled Release, 2024, 375, 829
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Continuous purification of mRNA by precipitation and sequential TFF

Maria del Carme Pons Royo, Tyler Arnold, Isabella Perez Rodriguez, Nicole Ostrovsky, Mushriq Al-Jazrawe, Andrew Hatas, Allan S. Myerson and Richard D. Braatz

Separation and Purification Technology, 2025, 379, 134837
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Oncolytic viruses and neoantigen vaccines: opportunities and challenges in priming antitumour immunity

André Mansinho, Joana Albuquerque and Emiliano Calvo

The Lancet Regional Health - Europe, 2026, 64, 101659
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Galloyl Dialkyl Lipids Drive Encapsulation of Peptides into Lipid Nanoparticles by Hydrogen Bonding

Tingting Ye, Yong Chen, Zifu Zhong, Yi Huang, Jamie De Baere, Mark Gontsarik, Kim Deswarte, Bianka Golba, Martijn Risseeuw, Serge Van Calenbergh, Bart N. Lambrecht and Bruno G. De Geest

J. Am. Chem. Soc., 2025, 147, 1307
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Current challenges and recent advances on the path towards continuous biomanufacturing

Milos Drobnjakovic, Roger Hart, Boonserm (Serm) Kulvatunyou, Nenad Ivezic and Vijay Srinivasan

Biotechnology Progress, 2023, 39
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Hyperspectral Imaging Techniques for Lyophilization: Advances in Data‐Driven Modeling Strategies and Applications

Huiwen Yu, Prakitr Srisuma, Cedric Devos, Jie Wang, Allan S. Myerson and Richard D. Braatz

Advanced Science, 2025, 12
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Long-term stability and immunogenicity of lipid nanoparticle COVID-19 mRNA vaccine is affected by particle size

Ruimeng Shi, Xueli Liu, Yajuan Wang, Meilu Pan, Shaoqin Wang, Lin Shi and Beibei Ni

Human Vaccines & Immunotherapeutics, 2024, 20
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Development of Thermally Stable mRNA-LNP Delivery Systems: Current Progress and Future Prospects

Urmila Kafle, Hoang Quan Truong, Cao Thuy Giang Nguyen and Fanfei Meng

Mol. Pharmaceutics, 2024, 21, 5944
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Expanding global access to mRNA vaccines

Behnaz Eshaghi, Robert Langer and Ana Jaklenec

Nat Rev Bioeng, 2026
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Effect of lipid composition on RNA-Lipid nanoparticle properties and their sensitivity to thin-film freezing and drying

Khaled AboulFotouh, Benjamin Southard, Huy M. Dao, Haiyue Xu, Chaeho Moon, Robert O. Williams III and Zhengrong Cui

International Journal of Pharmaceutics, 2024, 650, 123688
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Continuous manufacturing based paradigm shift in pharmaceuticals production and current regulatory framework

Kardile Punam Kashinath, Lohare Rahul Sanjay, Makka Krupali Ashokbhai, Subhadeep Roy, Md Samim Sardar and Santanu Kaity

Chemical Engineering Research and Design, 2025, 215, 1
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Admixing of mRNA with Pre‐Formed Lipid Nanoparticles Containing a Slightly‐Cationic Ionizable Lipid Allows for Efficient mRNA Transfection In Vitro and In Vivo

Haixiu Wang, Heleen Lauwers, Mark Gontsarik, Yong Chen, Niek N. Sanders, Miffy Hok Yan Cheng, Bruno G. De Geest and Zifu Zhong

Adv Healthcare Materials, 2025, 14
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Recent advances in drying and development of solid formulations for stable mRNA and siRNA lipid nanoparticles

Kinnari Santosh Arte, Manlin Chen, Chanakya D. Patil, Yijing Huang, Li Qu and Qi Zhou

Journal of Pharmaceutical Sciences, 2025, 114, 805
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Enabling mRNA Therapeutics: Current Landscape and Challenges in Manufacturing

Maryam Youssef, Cynthia Hitti, Julia Puppin Chaves Fulber and Amine A. Kamen

Biomolecules, 2023, 13, 1497
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Unraveling Lyophilization and Redispersion Effects on Miktoarm Polymer-Based Nanoformulations

Samaneh Yousefi Adlsadabad, Gabriel Théberge-Julien, Fatima Fernanda Portillo Gutierrez, Ricardo Beltran Medina, Ximena Matias Mercado, Éric Rhéaume, Jean-Claude Tardif and Ashok Kakkar

IJMS, 2025, 26, 10015
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Cancer/Testis Antigens as Targets for RNA-Based Anticancer Therapy

Kyeonghee Shim, Hyein Jo and Dooil Jeoung

IJMS, 2023, 24, 14679
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Advances in the design and delivery of RNA vaccines for infectious diseases

Abhijeet Girish Lokras, Thomas Rønnemoes Bobak, Saahil Sandeep Baghel, Federica Sebastiani and Camilla Foged

Advanced Drug Delivery Reviews, 2024, 213, 115419
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Advancements in breast cancer mRNA vaccines: Current development and future prospects

Wen Zheng, Wenjie Chen, Gyorgy Hutvagner, Laura Rangel-Sanchez and Wei Deng

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2026, 1881, 189515
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Advances in the development of lipid nanoparticles for ophthalmic therapeutics

Shen Chen, Zhihong Deng and Dan Ji

Biomedicine & Pharmacotherapy, 2024, 178, 117108
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Cryomilling of freeze dried low-Tg sugar glasses: A versatile method to prepare inhalable dry powder formulations

E.M. Jansen, S.A.E. Posthumus, M.K.T. Chan, M. Beertema, K.F. Mulia, H.W. Frijlink and W.L.J. Hinrichs

European Journal of Pharmaceutics and Biopharmaceutics, 2026, 223, 115065
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Tetrahydropyrimidine Ionizable Lipids for Efficient mRNA Delivery

Ivan Isaac, Altab Shaikh, Mayurakkhi Bhatia, Qian Liu, Seungman Park and Chandrabali Bhattacharya

ACS Nano, 2024, 18, 29045
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Recent advances in freeze-drying technologies for mRNA vaccines against infectious diseases

Jinghu Lou, Zhineng Wu, Yi Cheng, Meng Li, Nan Liu, Zengming Wang, Xiang Gao, Aiping Zheng and Hui Zhang

International Journal of Pharmaceutics, 2026, 687, 126426
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Freeze-Drying in Sucrose Followed by Cryomilling Enables the Formulation of sa-mRNA–LNP Powders for Inhalation

E. M. Jansen, M. J. R. Ruigrok, M. S. Suh, P. M. Ruppel, Xiaole Cui, L. Opsomer, N. N. Sanders, H. W. Frijlink and W. L. J. Hinrichs

Pharmaceutics, 2026, 18, 121
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