Quantitative Raman Chemical Imaging of Intracellular Drug-Membrane Aggregates and Small Molecule Drug Precipitates In Cytoplasmic Organelles

Adv Drug Deliv Rev. 2023 Sep 26:115107. doi: 10.1016/j.addr.2023.115107. Online ahead of print.ABSTRACTRaman confocal microscopes have been used to visualize the distribution of small molecule drugs within different subcellular compartments. This visualization allows the discovery, characterization, and detailed analysis of the molecular transport phenomena underpinning the Volume of Distribution - a key parameter governing the systemic pharmacokinetics of small molecule drugs. In the specific case of lipophilic small molecules with large Volumes of Distribution, chemical imaging studies using Raman confocal microscopes have revealed how weakly basic, poorly soluble drug molecules can accumulate inside cells by forming stable, supramolecular complexes in association with cytoplasmic membranes or by precipitating out within organelles. To study the self-assembly and function of the resulting intracellular drug inclusions, Raman chemical imaging methods have been developed to measure and map the mass, concentration, and ionization state of drug molecules at a microscopic, subcellular level. Beyond the field drug delivery, Raman chemical imaging techniques relevant to the study of microscopic drug precipitates and drug-lipid complexes which form inside cells are also being developed by researchers with seemingly unrelated scientific interests. Highlighting advances in data acquisition, calibration methods, and computational data management and analysis tools, this review will co...
Source: Advanced Drug Delivery Reviews - Category: Drugs & Pharmacology Authors: Source Type: research