TY  - JOUR
T1  - Nanocarrier Targeting Is Governed by Biological Access Before Ligand Affinity
A1  - João Silva
A1  - Pedro Costa
A1  - Ana Beatriz
JF  - International Journal of Pharmaceutical Research and Allied Sciences
JO  - Int J Pharm Res Allied Sci
SN  - 2277-3657
Y1  - 2024
VL  - 13
IS  - 2
DO  - 10.51847/QzNsfD43B3
SP  - 104
EP  - 113
N2  - Ligand–receptor affinity is often treated as the defining variable of active nanocarrier targeting, yet affinity can operate only after a carrier remains systemically available, reaches an accessible vascular segment, crosses or engages the endothelial barrier, traverses tissue, retains a biologically exposed ligand, and encounters a sufficiently available receptor. This Perspective argues that these preceding events should be treated as conditional access gates rather than background pharmacokinetics. Evidence from dose-dependent clearance, vessel-resolved permeability, transendothelial transport, tumour exit, interstitial pressure, macrophage redistribution, protein-corona remodeling, and single-particle ligand measurements shows that failure can arise before molecular recognition is possible. We therefore distinguish intrinsic affinity from biological access, functional ligand availability, receptor encounter, avidity, internalization, and payload availability. The resulting access-before-affinity interpretation is proposed as an evidence-bounded diagnostic logic, not as a universal quantitative law. It predicts that apparent targeting failure should first be localized to the earliest limiting biological compartment before affinity is optimized or blamed.
UR  - https://ijpras.com/article/nanocarrier-targeting-is-governed-by-biological-access-before-ligand-affinity-emjl06ti6ysi8sc
ER  -