Getting a drug into the brain may be only the first hurdle. 

 

A new multi-institutional review involving researchers from Birla Institute of Technology and Science, Pilani (BITS Pilani) and institutions in Taiwan warns that medicines capable of crossing the blood-brain barrier may still struggle to reach their intended targets and work effectively in an aging brain.

 

Published in the peer-reviewed journal Ageing Research Reviews, the review examines how age-related changes in the brain can alter the movement, distribution and effectiveness of advanced drug-delivery systems, particularly nanoparticles designed to carry medicines into the brain.

 

The review was authored by Ruei-Dun Teng, Jui-Ming Sun, Ting-Lin Yen, Cheng-Ta Hsieh and Chih-Hao Yang of Taipei Medical University and affiliated institutions in Taiwan, with Dr. Rajeev Taliyan, Neuropsychopharmacology Division, Department of Pharmacy, BITS Pilani, as a collaborating author.

 

Rajeev Taliyan, Neuropsychopharmacology Division, Department of Pharmacy, BITS Pilani, Pilani Campus, Rajasthan, India, said, “Crossing the blood-brain barrier is only the first step in delivering medicines to the brain. As we age, the brain undergoes several changes that can affect how a medicine reaches its target and how well it works. Understanding these changes can help us develop better and more precise treatments for brain disorders.”

 

The review highlights a critical gap in current drug-development approaches: many brain-targeted delivery systems are tested in young, healthy biological models, even though the patients ultimately receiving these treatments are often older adults with age-related changes in brain function.

 

With aging, blood vessels can become less flexible, fluid movement and waste-clearance processes can change, and immune activity can be altered. These changes can influence how nanoparticles travel through the brain, where they accumulate and how they release their therapeutic cargo.

 

That means a drug-delivery system that performs well in a young brain may behave differently in an older one.

 

The authors argue for drug-delivery systems designed with the changing biological environment of the aging brain in mind. Such systems could potentially respond to specific age- and disease-related changes, allowing medicines to be released under the conditions most appropriate for the individual patient.

 

The review also points to the potential importance of when a medicine is administered. Timing treatment according to biological rhythms, alongside patient-specific information, could help researchers determine more appropriate treatment strategies.

 

The researchers also call for drug-delivery systems to be tested in more advanced and realistic biological models before they reach patients.

 

Understanding how nanoparticles behave in the blood and brain of older individuals could provide important information about their safety, distribution and effectiveness—and help close the gap between promising laboratory results and real-world treatment.

 

The central message of the review is clear: successfully crossing the blood-brain barrier should not be treated as the finish line for brain drug delivery.

 

Researchers must also understand what happens to a medicine after it enters the brain, particularly in the aging brain where changes in blood flow, waste clearance and immune activity can alter its journey.

 

The authors suggest that this broader, age-aware approach could help guide the development of safer and more effective treatments for age-related neurological disorders, including Alzheimer’s and Parkinson’s diseases.