Researchers from Birla Institute of Technology and Science, Pilani (BITS Pilani) and institutions in Taiwan have highlighted a key challenge in developing treatments for brain disorders: getting a medicine across the blood-brain barrier does not necessarily mean that it will reach the right target or work effectively in an ageing brain.
The findings are part of a multi-institutional review published in the peer-reviewed journal Ageing Research Reviews. The review examines how age-related changes in the brain can influence the movement, distribution and effectiveness of nanoparticles used to deliver medicines.
Ageing alters drug delivery environment
The review explains that the ageing brain undergoes changes in blood flow, fluid movement, waste clearance and immune activity. These changes can affect how nanoparticles move through brain tissue, where they accumulate and how efficiently they release their therapeutic payload.
The researchers point out that many drug-delivery systems are evaluated in young, healthy biological models, which may not accurately represent conditions in older patients.
As people age, blood vessels can lose flexibility, the brain’s waste-clearance mechanisms may become less efficient and changes in immune activity can alter the way nanoparticles behave. Consequently, a drug-delivery system that performs effectively in a young brain may behave differently in an ageing brain.
Call for age-specific drug delivery
The review argues for the development of drug-delivery systems capable of responding to the changing biological conditions associated with ageing and disease.
Such systems could potentially release medicines in response to specific age- or disease-related changes in the brain. The researchers also highlight the potential role of treatment timing and patient-specific information in determining the most appropriate therapeutic approach.
BITS Pilani, Neuropsychopharmacology Division, Department of Pharmacy, Dr Rajeev Taliyan 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.”
Need for realistic testing
The researchers emphasise the need to test nanoparticle-based drug-delivery systems in more advanced and realistic biological models before they are considered for clinical application.
Understanding how nanoparticles behave in the blood and brain of older individuals could help researchers assess their safety, distribution and therapeutic effectiveness more accurately.
The review calls for a broader approach to brain-targeted drug development, moving beyond the question of whether a medicine can cross the blood-brain barrier to examining what happens after it enters the brain.
Such an approach could support the development of more targeted and potentially safer treatments for age-related neurological conditions, including Alzheimer’s and Parkinson’s diseases.