TY  - JOUR
T1  - Targeted Delivery Should Be Designed Around Competing Biological Sinks
A1  - Elena Fedorova
A1  - Alexey Volkov
A1  - Irina Morozova
A1  - Dmitry Kuznetsov
JF  - International Journal of Pharmaceutical Research and Allied Sciences
JO  - Int J Pharm Res Allied Sci
SN  - 2277-3657
Y1  - 2026
VL  - 15
IS  - 3
DO  - 10.51847/pUtYVqZdFi
SP  - 38
EP  - 50
N2  - Targeted drug delivery is usually framed as a problem of increasing affinity for a desired tissue or cell. That framing is incomplete because an administered carrier is simultaneously exposed to biological compartments that remove, retain, transform, redistribute, or consume it before and after target contact. These competing sinks include the mononuclear phagocyte system, liver and spleen, renal and pulmonary pathways, adsorbed proteins, nontarget cellular populations, and finite receptor pools at the intended destination. Their influence is dynamic rather than fixed: formulation composition, acquired biological identity, administration route, dose, tissue state, receptor abundance, and time can change the relative strength of each pathway. This Systems Perspective argues that targeted delivery should therefore be designed as an exposure-allocation problem. Target accumulation represents only one term in a broader system of competing fluxes, retention processes, capacity limits, and exit routes. Evidence from nanomedicine biodistribution, tumor transport, lipid nanoparticles, renal and pulmonary targeting, protein-corona biology, and receptor-density studies is used to distinguish established mechanisms from a proposed competing-sinks interpretation. Particular attention is given to conditions in which apparently improved targeting redistributes exposure toward another organ, increases nonproductive cellular binding, saturates clearance, perturbs receptor availability, or introduces a new safety liability. The resulting perspective does not provide a validated quantitative predictor. Instead, it proposes a mass-balance-oriented design logic in which target exposure must be interpreted against simultaneous changes in competing biological sinks and verified using measurements that preserve tissue, cellular, temporal, dose, and translational boundaries.
UR  - https://ijpras.com/article/targeted-delivery-should-be-designed-around-competing-biological-sinks-1pjpltyqx5glr60
ER  -