Placenta-Targeted Precision Pharmacotherapy During Pregnancy: Systematic Review of Pharmacokinetic Changes, Placental Drug Transport and Emerging Maternal–Foetal Drug-Delivery Strategies

Abstract

Pregnancy presents a persistent therapeutic dilemma. Physiological adaptations that are essential for maternal and foetal well-being simultaneously alter the pharmacokinetic behaviour of many medications, often making conventional dosing strategies less predictable. At the same time, the placenta functions as a dynamic biological interface rather than a passive barrier, actively regulating the movement of drugs between maternal and foetal circulations. Although substantial progress has been made in understanding pregnancy-associated pharmacokinetic changes and placental transport mechanisms, these areas have frequently been investigated in isolation. The growing emergence of placenta-targeted drug-delivery technologies has created a need for a more integrated perspective. This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses principles to synthesise the current evidence on pregnancy-induced pharmacokinetic alterations, mechanisms governing placental drug transport and emerging strategies for placenta-directed therapeutic delivery. Literature from major biomedical databases was evaluated through a structured screening process, resulting in the inclusion of 34 studies encompassing pharmacokinetic investigations, placental transport research, experimental models and translational drug-delivery approaches. The evidence consistently demonstrates that gestational changes in maternal physiology influence drug absorption, distribution, metabolism and elimination, while placental transporters and metabolic systems further shape foetal drug exposure. Recent advances in trophoblast-targeted liposomes, lipid nanoparticles, extracellular vesicles and other precision-delivery platforms suggest that selective placental targeting may improve therapeutic efficacy while reducing unintended foetal exposure. The available evidence supports a shift from conventional maternal pharmacotherapy towards a more precise maternal–foetal therapeutic framework. Future progress will depend on the integration of mechanistic placental biology, advanced delivery technologies and clinically relevant translational models capable of bridging experimental innovation with safe and effective pregnancy care.