Pomegranate Seed Oil Biologically Engineered Lactobacillus Extracellular Vesicles with Enhanced Yield and Brain Delivery via ApoE-Enriched Protein Corona
- 1Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, People's Republic of China.
- 2Meishan Engineering & Technology Research Center for Extraction and Transformation of Effective Components in Chinese Medicinal Herbs, Meishan Vocational & Technical College, Meishan, 620010, People's Republic of China.
- 3School of Basic Medical Science, Chengdu University, Chengdu, 610106, People's Republic of China.
Abstract
Dongyan Duan,1,* Shuhui Xu,1,* Keying Wu,2 Meisha Xu,1 Shuya Zhou,1 Xinru Yang,1 Xiaoqiang Guo,1 Shuo Yan,3 Jun Yan,1 Qian Yao11Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, People’s Republic of China; 2Meishan Engineering & Technology Research Center for Extraction and Transformation of Effective Components in Chinese Medicinal Herbs, Meishan Vocational & Technical College, Meishan, 620010, People’s Republic of China; 3School of Basic Medical Science, Chengdu University, Chengdu, 610106, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian Yao, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Shiling Town, Longquan District, Chengdu, Sichuan, 610106, People’s Republic of China, Tel +86-28-84616387, Email [email protected]: The blood–brain barrier (BBB) is a major bottleneck for nanomedicine-based treatment of central nervous system (CNS) disorders. Lactobacillus-derived extracellular vesicles (LEV) are promising biocompatible nanocarriers, but their low production yield and limited BBB permeability hinder their development. We hypothesized that stimulation of Lactobacillus with pomegranate seed oil (PSO), or its nanoemulsion (PSO NE), could remodel the LEV membrane to simultaneously enhance vesicle production and brain accumulation.Methods: Lactobacillus was stimulated with PSO or PSO NE to generate engineered LEV. Lipidomic and proteomic analyses were performed to characterize membrane remodeling and plasma protein corona formation. Oleuropein (OL) was loaded into different LEV formulations, and their BBB permeability and brain accumulation were evaluated in vivo. The anti-amyloid β (Aβ) aggregation activity and biocompatibility of the engineered LEVs were also assessed.Results: PSO and PSO NE increased LEV production by approximately 3- and 5-fold, respectively, while markedly remodeling their membrane composition, with enrichment of phospholipids, triglycerides, and apolipoproteins. Upon exposure to plasma, the remodeled LEVs spontaneously acquired an apolipoprotein E (ApoE)-rich protein corona, facilitating BBB transport through low-density lipoprotein receptor (LDLR)-mediated transcytosis. Accordingly, OL-loaded LEV-PSO and LEV-PSO NE achieved 5– 7-fold higher brain exposure than free OL, compared with only a 1.17-fold increase for conventional OL@LEV. Both native and OL-loaded LEVs inhibited Aβ aggregation, with OL-loaded formulations showing stronger activity. Repeated administration for 14 days demonstrated good biocompatibility and significantly increased BBB LDLR expression following LEV-PSO and LEV-PSO NE treatment.Conclusion: PSO-mediated membrane engineering substantially improves LEV production and BBB transport through protein-corona modulation, providing a scalable and versatile platform for CNS drug delivery.Keywords: Lactobacillus extracellular vesicles, membrane engineering, protein Corona, brain delivery, pomegranate seed oil, Alzheimer’s disease
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BibTeX
@article{duan2026pomegranate,
title = {{Pomegranate Seed Oil Biologically Engineered Lactobacillus Extracellular Vesicles with Enhanced Yield and Brain Delivery via ApoE-Enriched Protein Corona}},
author = {Dongyan Duan and Shuhui Xu and Keying Wu and Meisha Xu and Shuya Zhou and Xinru Yang and Xiaoqiang Guo and Shuo Yan and Jun Yan and Qian Yao},
journal = {International Journal of Nanomedicine},
year = {2026},
month = nov,
doi = {10.2147/ijn.s636377},
url = {https://www.dovepress.com/pomegranate-seed-oil-biologically-engineered-lactobacillus-extracellul-peer-reviewed-fulltext-article-IJN},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Pomegranate Seed Oil Biologically Engineered Lactobacillus Extracellular Vesicles with Enhanced Yield and Brain Delivery via ApoE-Enriched Protein Corona
AU - Dongyan Duan
AU - Shuhui Xu
AU - Keying Wu
AU - Meisha Xu
AU - Shuya Zhou
AU - Xinru Yang
AU - Xiaoqiang Guo
AU - Shuo Yan
AU - Jun Yan
AU - Qian Yao
PY - 2026
DA - 2026/11/03
JO - International Journal of Nanomedicine
DO - 10.2147/ijn.s636377
UR - https://www.dovepress.com/pomegranate-seed-oil-biologically-engineered-lactobacillus-extracellul-peer-reviewed-fulltext-article-IJN
AB - Dongyan Duan,1,* Shuhui Xu,1,* Keying Wu,2 Meisha Xu,1 Shuya Zhou,1 Xinru Yang,1 Xiaoqiang Guo,1 Shuo Yan,3 Jun Yan,1 Qian Yao11Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, People’s Republic of China; 2Meishan Engineering & Technology Research Center for Extraction and Transformation of Effective Components in Chinese Medicinal Herbs, Meishan Vocational & Technical College, Meishan, 620010, People’s Republic of China; 3School of Basic Medical Science, Chengdu University, Chengdu, 610106, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian Yao, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Shiling Town, Longquan District, Chengdu, Sichuan, 610106, People’s Republic of China, Tel +86-28-84616387, Email [email protected]: The blood–brain barrier (BBB) is a major bottleneck for nanomedicine-based treatment of central nervous system (CNS) disorders. Lactobacillus-derived extracellular vesicles (LEV) are promising biocompatible nanocarriers, but their low production yield and limited BBB permeability hinder their development. We hypothesized that stimulation of Lactobacillus with pomegranate seed oil (PSO), or its nanoemulsion (PSO NE), could remodel the LEV membrane to simultaneously enhance vesicle production and brain accumulation.Methods: Lactobacillus was stimulated with PSO or PSO NE to generate engineered LEV. Lipidomic and proteomic analyses were performed to characterize membrane remodeling and plasma protein corona formation. Oleuropein (OL) was loaded into different LEV formulations, and their BBB permeability and brain accumulation were evaluated in vivo. The anti-amyloid β (Aβ) aggregation activity and biocompatibility of the engineered LEVs were also assessed.Results: PSO and PSO NE increased LEV production by approximately 3- and 5-fold, respectively, while markedly remodeling their membrane composition, with enrichment of phospholipids, triglycerides, and apolipoproteins. Upon exposure to plasma, the remodeled LEVs spontaneously acquired an apolipoprotein E (ApoE)-rich protein corona, facilitating BBB transport through low-density lipoprotein receptor (LDLR)-mediated transcytosis. Accordingly, OL-loaded LEV-PSO and LEV-PSO NE achieved 5– 7-fold higher brain exposure than free OL, compared with only a 1.17-fold increase for conventional OL@LEV. Both native and OL-loaded LEVs inhibited Aβ aggregation, with OL-loaded formulations showing stronger activity. Repeated administration for 14 days demonstrated good biocompatibility and significantly increased BBB LDLR expression following LEV-PSO and LEV-PSO NE treatment.Conclusion: PSO-mediated membrane engineering substantially improves LEV production and BBB transport through protein-corona modulation, providing a scalable and versatile platform for CNS drug delivery.Keywords: Lactobacillus extracellular vesicles, membrane engineering, protein Corona, brain delivery, pomegranate seed oil, Alzheimer’s disease
SN - 1178-2013
SN - 1176-9114
ER -