en تخصصي Special كاربردي Applicable <span style="font-size:10pt"><span style="line-height:115%"><span style="font-family:&quot;Times New Roman&quot;,&quot;serif&quot;">Efficient delivery of therapeutic agents to the central nervous system (CNS) remains challenging due to the restrictive blood&ndash;brain barrier (BBB). This review evaluates physiological and pharmaceutical determinants of brain bioavailability and discusses emerging nanotechnology-based strategies. Brain bioavailability is influenced by BBB integrity, efflux transporter activity, cerebral blood flow, pathological conditions, molecular properties, and nanocarrier design. Integrating physiological understanding with rational pharmaceutical design is essential for improving future CNS therapeutics.</span></span></span><br> <br> &nbsp; Blood–brain barrier, Brain bioavailability, CNS drug delivery, Efflux transporters, Nanoparticles, Receptor-mediated transport, Intranasal delivery 123 132 http://ajpr.umsha.ac.ir/browse.php?a_code=A-10-2-92&slc_lang=en&sid=1 Fatemeh Shariat Razavi shariatrazavif@gmail.com No 1 Department of Pharmaceutics, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran