Academic Journal
Lactoferrin-Modified Ultra-Sustained Release Propofol Nanoparticles for Multi-Pathway Therapy of Depression via Intraperitoneal Injection.
| Τίτλος: | Lactoferrin-Modified Ultra-Sustained Release Propofol Nanoparticles for Multi-Pathway Therapy of Depression via Intraperitoneal Injection. |
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| Συγγραφείς: | Wu Z; Department of Psychiatry and Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.; Yan'an Medical College of Yan'an University, Yan'an, Shaanxi, People's Republic of China., Deng J; Department of Psychiatry and Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.; Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People's Republic of China., Li S; Department of Psychiatry and Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.; Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People's Republic of China., Yu L; Center for Translational Medicine, The First Affiliated Hospital of Xi' an Jiaotong University, Xi'an, Shaanxi, People's Republic of China., Zhang H; Department of Psychiatry and Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.; Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People's Republic of China., Xun Y; Center for Translational Medicine, The First Affiliated Hospital of Xi' an Jiaotong University, Xi'an, Shaanxi, People's Republic of China., Bian J; Department of Psychiatry and Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China., Liu J; Center for Translational Medicine, The First Affiliated Hospital of Xi' an Jiaotong University, Xi'an, Shaanxi, People's Republic of China., Zhang J; College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China., Lei P; Department of Psychiatry and Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China., Ma Q; Department of Psychiatry and Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China., Fan Y; Department of Psychiatry and Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China., Yang Z; Department of Psychiatry and Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China., Zhu F; Department of Psychiatry and Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China., Ma X; Department of Psychiatry and Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China., Wu D; Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China., Zhang S; Department of Psychiatry and Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China. |
| Πηγή: | International journal of nanomedicine [Int J Nanomedicine] 2026 Oct 14; Vol. 21, pp. 645818. Date of Electronic Publication: 2026 Oct 14 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: DOVE Medical Press Country of Publication: New Zealand NLM ID: 101263847 Publication Model: eCollection Cited Medium: Internet ISSN: 1178-2013 (Electronic) Linking ISSN: 11769114 NLM ISO Abbreviation: Int J Nanomedicine Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Auckland : DOVE Medical Press |
| Ιατρικοί όροι (MeSH): | Propofol*/chemistry , Propofol*/pharmacokinetics , Propofol*/administration & dosage , Propofol*/pharmacology , Depression*/drug therapy , Nanoparticles*/chemistry , Nanoparticles*/administration & dosage , Lactoferrin*/chemistry , Lactoferrin*/pharmacokinetics , Antidepressive Agents*/pharmacokinetics , Antidepressive Agents*/chemistry , Antidepressive Agents*/administration & dosage , Antidepressive Agents*/pharmacology, Delayed-Action Preparations/chemistry ; Delayed-Action Preparations/pharmacokinetics ; Delayed-Action Preparations/administration & dosage ; Delayed-Action Preparations/pharmacology ; Brain/metabolism ; Brain/drug effects ; Animals ; Mice ; Injections, Intraperitoneal ; Male |
| Περίληψη: | Background: Depression imposes a significant burden on global public health, and traditional antidepressants are limited by slow onset, low efficacy, and high recurrence rates. Intraperitoneal injection of propofol can rapidly exert anti-anhedonic effects by regulating the VTA-NAc dopaminergic and GABAergic signaling pathways. However, its application in depression treatment is limited by rapid systemic clearance, poor brain permeability, and significant systemic toxicity. Moreover, the simple lipophilic structure of propofol and the limited drug-loading and long-term controlled-release performance of conventional physically encapsulated nanocarriers hinder the development of long-acting propofol formulations. Methods: Lactoferrin-functionalized PVA-propofol nanoparticles (LF-PVA@Pro NPs) were prepared based on the strong intermolecular affinity between PVA and propofol, as validated by molecular dynamics simulations. Their physicochemical properties, in vitro release behavior, brain-targeting efficiency, biosafety, and in vivo antidepressant efficacy were systematically characterized using CRS-induced depressive mouse models through multiple behavioral and histological assessments. Results: LF-PVA@Pro NPs achieved a drug loading of 19.3% and exhibited sustained in vitro release for 100 h. Following intraperitoneal injection, the formulation maintained therapeutic brain concentrations for 100 h (6-8-fold longer than free propofol) and increased cerebral drug accumulation by 2.5-fold. Its LD50 was 2802 mg/kg, 2.36-fold higher than that of free propofol, ensuring safety at the therapeutic dose of 40 mg/kg. In vivo studies demonstrated that LF-PVA@Pro NPs markedly alleviated depressive- and anxiety-like phenotypes, reduced VTA/NAc neuronal injury, and restored c-Fos, GABA, and DAT expression, thereby reactivating reward circuits. Conclusion: LF-modified ultra-sustained brain-targeted nanoparticles enable multi-pathway long-term depression intervention, offering a translatable strategy to repurpose propofol as a rapid-onset antidepressant for chronic stress-related depression. (© 2026 Wu et al.) |
| Competing Interests: | The authors report no conflicts of interest in this work. |
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| Contributed Indexing: | Keywords: depression; molecular dynamics simulations; multi-pathway therapy; propofol nanoparticles; ultra-sustained release |
| Substance Nomenclature: | YI7VU623SF (Propofol) 0 (Delayed-Action Preparations) EC 3.4.21.- (Lactoferrin) 0 (Antidepressive Agents) |
| Entry Date(s): | Date Created: 20261020 Date Completed: 20261020 Latest Revision: 20261022 |
| Update Code: | 20261022 |
| PubMed Central ID: | PMC13678437 |
| DOI: | 10.2147/IJN.S645818 |
| PMID: | 42898626 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1178-2013 |
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| DOI: | 10.2147/IJN.S645818 |