Topics in medicinal chemistry, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
Biomacromolecules, Год журнала: 2025, Номер 26(1), С. 623 - 634
Опубликована: Янв. 2, 2025
mRNA-based therapies hold tremendous promise for treating various diseases, yet their clinical success is hindered by delivery challenges. This study developed a library of 140 lipocationic Poly(β-amino ester)s (PBAEs) and formulated lipid-polymer hybrid nanoparticles (LPHs) with four helper lipids, including 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), to enhance mRNA delivery. Initial in vitro screening representative PBAEs identified the D/P4-1 formulation (DOTAP/PBAE molar ratio 4:1) as most effective. Further using this eight top-performing LPHs. In vivo experiments confirmed high luciferase expression spleen lungs mice following intravenous administration Luc mRNA-loaded Detailed analysis revealed that DOTAP incorporation influenced LPH properties, apparent pKa, surface charge, internal hydrophobicity, enabling enhanced release cellular uptake. demonstrates potent approaches modulate PBAE-lipid nanoparticle properties altering PBAE structures composition, offering insights designing effective carriers therapeutics.
Язык: Английский
Процитировано
1
Advanced Materials, Год журнала: 2025, Номер unknown
Опубликована: Апрель 1, 2025
mRNA therapeutics hold tremendous promise for disease prevention and treatment. Development of high-performance delivery systems with enhanced transfection efficiency a safety profile will further fulfill their therapeutic potential expedite translation. The synthesis "four-in-one" highly branched poly(β-amino ester)s (O-LhPAEs) is reported by integrating the essential components lipid nanoparticles (LNPs) spleen-selective enrichment nebulization treatment silicosis. 60 O-LhPAEs distinct structure chemical composition, including tertiary/quaternary amines, cholesterol moieties, zwitterionic species, hydrophobic alkyl tails, are synthesized using sequential Michael addition, ring-opening, nucleophilic substitution reactions. unique topological composition collectively O-LhPAEs/mRNA polyplex serum resistance, cellular uptake, endosomal escape. optimal O-LhPAE, 20%b-3C-2P12, exhibits up to 93.1% across 11 different cell types, epithelial cells, fibroblasts, cancer stem neurological astrocytes. Biodistribution study reveals that 20%b-3C-2P12/mRNA polyplexes mainly enriched in spleen following systemic administration. Through nebulization, 20%b-3C-2P12 mediated high Tbx2 expression lungs silicosis mice, effectively restoring lung functions. This not only establishes strategy development LNP-like but also provides promising candidates safe, efficient,
Язык: Английский
Процитировано
1
Pharmaceutics, Год журнала: 2024, Номер 16(7), С. 918 - 918
Опубликована: Июль 10, 2024
Drug development costs can be significantly reduced if proven “platform” technologies are allowed to used without having validate their use. The most recent US Food and Administration (FDA) guideline brings more clarity, as well a greater focus on the complex that now for faster drug development. FDA has highlights use of lipid nanoparticles (LNPs) package deliver mRNA vaccines, gene therapy, short (2–20 length) synthetic nucleotides (siRNA). Additionally, monoclonal antibody cell is targeted. provides systematic process requesting platform status benefit from its advantages. It advanced science rationality into regulatory steps FDA’s approval drugs biologicals.
Язык: Английский
Процитировано
5
Polymer-Plastics Technology and Materials, Год журнала: 2024, Номер unknown, С. 1 - 23
Опубликована: Дек. 16, 2024
Polymers have become a versatile tool in pharmaceutical chemistry through techniques and new formulation. This review presents an overview of the general topic drug delivery polymers, places particular focus on their specific contributions, discusses significant issues like biocompatibility, controlled release targeted delivery. Unlike previous reviews, it captures recent development biodegradable, smart stimuli-responsive abilities to improve therapy outcomes patient adherence treatments. Furthermore, this work also has enhanced understanding advanced polymer-based systems such as polymeric nanoparticles, bioconjugation strategies natural with examples various therapeutic areas. The stands for itself by expanding discussion regulatory clinical realism difficulties well safety, efficacy, acceptance considerations. In addition, emphasizes role interdisciplinary intersectoral cooperation cross-country collaborations developing polymers-based applications precision medicine. way, provides fresh view both present advancements future possibilities technologies dedicated achievements globally inspire researchers practitioners.
Язык: Английский
Процитировано
4
Asian Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер 20(1), С. 101015 - 101015
Опубликована: Янв. 5, 2025
The recent commercialization of gene products has sparked significant interest in therapy, necessitating efficient and precise delivery via various vectors. Currently, viral vectors lipid-based nanocarriers are the predominant choices have been extensively investigated reviewed. Beyond these vectors, polymeric also hold promise therapeutic owing to their versatile functionalities, such as improving stability, cellar uptake endosomal escape nucleic acid drugs, along with targeted tissues. This review presents a brief overview status quo emerging for delivery, focusing on key cationic polymers, nanocarrier types, preparation methods. It highlights diseases, strategies improve efficiency, potential future directions this research area. is hoped inspire development, optimization, clinical translation highly delivery.
Язык: Английский
Процитировано
0
Frontiers in Nanotechnology, Год журнала: 2025, Номер 7
Опубликована: Фев. 12, 2025
Cancer is a leading cause of death worldwide, with an estimated 20 million new cancer cases and 9.7 deaths worldwide in 2022. Immunotherapy provides innovative strategies among the most groundbreaking developments treatment. vaccines, as form immunotherapy, have great prospect to help patients resistant other standard-of-care immunotherapies. On hand, various properties nanomaterials play essential role collecting, maturation, activation immune system. vaccines based on (also called nanovaccines) can be specifically delivered target tissues cells through nanocarriers nanoplatforms, thereby improving efficacy, extending duration antitumor immunity, minimizing side effects. This paper reviewed research progress some nanovaccines including polymer nanoparticle vaccine, liposome cell-based inorganic adjuvant auxiliary work. We believe that nanoparticle-based widespread applications currently, while using mRNA are expected see greater development future. also think prevention treatment, especially prolonging life span patients.
Язык: Английский
Процитировано
0
Journal of Controlled Release, Год журнала: 2025, Номер 381, С. 113581 - 113581
Опубликована: Фев. 26, 2025
Язык: Английский
Процитировано
0
Polymer science & technology., Год журнала: 2025, Номер unknown
Опубликована: Апрель 10, 2025
Язык: Английский
Процитировано
0
Chemistry of Materials, Год журнала: 2025, Номер unknown
Опубликована: Апрель 11, 2025
Язык: Английский
Процитировано
0
Lab on a Chip, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
Synthesis of nanoparticles (NPs) has garnered significant interest due to their wide-ranging applications. Microfluidics offers a superior alternative traditional NPs synthesis by providing precise control over reaction parameters.
Язык: Английский
Процитировано
0