16.9: Modified-Release Drug Delivery Systems: Site-Targeted

Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions. Third-order enables intracellular drug delivery for enhanced efficacy in genetic and cytotoxic therapies. Passive targeting utilizes the physicochemical properties of carrier systems, such as size and charge, to enhance drug accumulation at specific sites via the enhanced permeability and retention (EPR) effect. Active targeting involves ligands or monoclonal antibodies binding to specific cell receptors, ensuring selective uptake and reduced off-target effects.

Carriers protect drugs, improve uptake, and reduce premature clearance through covalent or non-covalent bonding. Polymeric carriers generally contain a backbone, homing device, solubilizer, and spacer-linked drug, facilitating controlled drug release. Biodegradable micro- and nanoparticles further improve targeting by prolonging circulation and site-specific accumulation. Albumin-based carriers prolong drug action by reducing renal clearance. Lipoproteins facilitate intracellular drug transport through receptor-mediated endocytosis. Liposomes enhance drug solubility and stability while reducing systemic toxicity. Immunoliposomes, incorporating monoclonal antibodies in liposomal bilayers, enable precise targeting of diseased cells.

Nanotechnology and molecular biology advances continue to refine targeted drug delivery, integrating biomimetic materials, stimuli-responsive release, and multifunctional nanocarriers for higher specificity and efficacy in personalized medicine.

Site-targeted drug delivery systems enhance therapeutic efficacy while reducing side effects and treatment costs associated with conventional approaches.

These systems can be categorized into four orders of targeting. First-order systems passively direct drugs to the capillary bed of organs or tissues, while second-order systems target specific cells, such as tumor cells.

Third-order systems facilitate intracellular drug delivery, while fourth-order systems target macromolecules.

Additionally, passive targeting relies on the carrier system’s physicochemical properties. In contrast, active targeting employs ligands or monoclonal antibodies to improve drug specificity.

Drug carriers protect drugs, improve uptake, and reduce clearance through covalent or non-covalent bonding.

Polymeric carriers typically comprise a polymeric backbone, a targeting ligand, a solubilizer, and a spacer that covalently links the drug.

Other carriers include albumin, which prolongs drug action; lipoproteins, which support intracellular drug transport; and liposomes, which improve efficacy and reduce side effects.