Extracellular vesicles (EVs) have emerged as highly promising nanocarriers for drug delivery, due to their biocompatibility, stability, and natural cell-targeting capabilities. Among the various sources of EVs, milk-derived EVs (MDEVs) have gained considerable attention for their abundance, cost-effectiveness, and distinctive biological properties. This review offers an in-depth analysis of MDEVs as potential carriers for oral drug delivery and their therapeutic applications. The review begins with an overview of the characteristics of EVs, highlighting the unique attributes of MDEVs. It proceeds to explore the different methods of isolation and purification, emphasizing those that maintain structural integrity and preserve biological activity. Furthermore, the regenerative potential of MDEVs is examined across multiple domains, including dermatology (skin wound healing and cosmetic applications), hair regeneration, and treatment of inflammatory diseases. Particular focus is given to the suitability of MDEVs for oral drug delivery, stressing their remarkable stability within the gastrointestinal tract, their ability to enhance bioavailability, and their capacity to traverse the intestinal barrier. The review also analyzes case studies of MDEV-based oral delivery systems used for treating intestinal diseases and systemic conditions, such as cancer. Finally, the review addresses the current challenges in the field, offers perspectives on future directions, and evaluates the clinical potential of MDEVbased therapies. This study provides valuable insights into the evolving field of milk-derived EVs and their applications in oral drug delivery and regenerative medicine.

Extracellular vesicles (EVs) have emerged as highly promising nanocarriers for drug delivery, due to their biocompatibility, stability, and natural cell-targeting capabilities. Among the various sources of EVs, milk-derived EVs (MDEVs) have gained considerable attention for their abundance, cost-effectiveness, and distinctive biological properties. This review offers an in-depth analysis of MDEVs as potential carriers for oral drug delivery and their therapeutic applications. The review begins with an overview of the characteristics of EVs, highlighting the unique attributes of MDEVs. It proceeds to explore the different methods of isolation and purification, emphasizing those that maintain structural integrity and preserve biological activity. Furthermore, the regenerative potential of MDEVs is examined across multiple domains, including dermatology (skin wound healing and cosmetic applications), hair regeneration, and treatment of inflammatory diseases. Particular focus is given to the suitability of MDEVs for oral drug delivery, stressing their remarkable stability within the gastrointestinal tract, their ability to enhance bioavailability, and their capacity to traverse the intestinal barrier. The review also analyzes case studies of MDEV-based oral delivery systems used for treating intestinal diseases and systemic conditions, such as cancer. Finally, the review addresses the current challenges in the field, offers perspectives on future directions, and evaluates the clinical potential of MDEVbased therapies. This study provides valuable insights into the evolving field of milk-derived EVs and their applications in oral drug delivery and regenerative medicine.

Extracellular vesicles (EVs) have emerged as highly promising nanocarriers for drug delivery, due to their biocompatibility, stability, and natural cell-targeting capabilities. Among the various sources of EVs, milk-derived EVs (MDEVs) have gained considerable attention for their abundance, cost-effectiveness, and distinctive biological properties. This review offers an in-depth analysis of MDEVs as potential carriers for oral drug delivery and their therapeutic applications. The review begins with an overview of the characteristics of EVs, highlighting the unique attributes of MDEVs. It proceeds to explore the different methods of isolation and purification, emphasizing those that maintain structural integrity and preserve biological activity. Furthermore, the regenerative potential of MDEVs is examined across multiple domains, including dermatology (skin wound healing and cosmetic applications), hair regeneration, and treatment of inflammatory diseases. Particular focus is given to the suitability of MDEVs for oral drug delivery, stressing their remarkable stability within the gastrointestinal tract, their ability to enhance bioavailability, and their capacity to traverse the intestinal barrier. The review also analyzes case studies of MDEV-based oral delivery systems used for treating intestinal diseases and systemic conditions, such as cancer. Finally, the review addresses the current challenges in the field, offers perspectives on future directions, and evaluates the clinical potential of MDEVbased therapies. This study provides valuable insights into the evolving field of milk-derived EVs and their applications in oral drug delivery and regenerative medicine.

Cognitive impairments and motor dysfunction are commonly observed behavioral phenotypes in genetic animal models of neurodegenerative diseases. JNPL3 transgenic mice expressing human P301L-mutant tau display motor disturbances with age- and gene dose-dependent development of neurofibrillary tangles, suggesting that tau pathology causes neurodegeneration associated with motor behavioral abnormalities. Although gait ignition failure (GIF), a syndrome marked by difficulty in initiating locomotion, has been described in patients with certain forms of tauopathies, transgenic mouse models mirroring human GIF syndrome have yet to be reported. Using the open field and balance beam tests, here we discovered that JNPL3 homozygous mice exhibit a marked delay of movement initiation. The elevated plus maze excluded the possibility that hesitation to start in JNPL3 mice was caused by enhanced levels of anxiety. Considering the normal gait ignition in rTg4510 mice expressing the same mutant tau in the forebrain, GIF in JNPL3 mice seems to arise from abnormal tau deposition in the hindbrain areas involved in locomotor initiation. Accordingly, immunohistochemistry revealed highly phosphorylated paired helical filament tau in JNPL3 brainstem areas associated with gait initiation. Together, these findings demonstrate a novel behavioral phenotype of impaired gait initiation in JNPL3 mice and underscore the value of this mouse line as a tool to study the neural mechanisms and potential treatments for human GIF syndrome.
Animals ; Anxiety ; Brain Stem ; Cognition Disorders ; Gait ; Humans ; Immunohistochemistry ; Locomotion ; Mice ; Mice, Transgenic ; Models, Animal ; Neurodegenerative Diseases ; Neurofibrillary Tangles ; Pathology ; Phenotype ; Prosencephalon ; Rhombencephalon ; Tauopathies