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Safety of surfactant excipients in oral drug formulations.

Surfactants are a diverse group of compounds that share the capacity to adsorb at the boundary between distinct phases of matter. They are used as pharmaceutical excipients, food additives, emulsifiers in cosmetics, and as household/industrial detergents. This review outlines the interaction of surfactant-type excipients present in oral pharmaceutical dosage forms with the intestinal epithelium of the gastrointestinal (GI) tract. Many surfactants permitted for human consumption in oral products reduce intestinal epithelial cell viability in vitro and alter barrier integrity in epithelial cell monolayers, isolated GI tissue mucosae, and in animal models. This suggests a degree of mis-match for predicting safety issues in humans from such models. Recent controversial preclinical research also infers that some widely used emulsifiers used in oral products may be linked to ulcerative colitis, some metabolic disorders, and cancers. We review a wide range of surfactant excipients in oral dosage forms regarding their interactions with the GI tract. Safety data is reviewed across in vitro, ex vivo, pre-clinical animal, and human studies. The factors that may mitigate against some of the potentially abrasive effects of surfactants on GI epithelia observed in pre-clinical studies are summarised. We conclude with a perspective on the overall safety of surfactants in oral pharmaceutical dosage forms, which has relevance for delivery system development.

Quantitative Raman chemical imaging of intracellular drug-membrane aggregates and small molecule drug precipitates in cytoplasmic organelles.

Raman 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 of 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 cover a decade of technological developments that enable the conversion of spectral signals obtained from Raman confocal microscopes into new discoveries and information about previously unknown, concentrative drug transport pathways driven by soluble-to-insoluble phase transitions occurring within the cytoplasmic organelles of eukaryotic cells.

Lipid bilayer-based biological nanoplatforms for sonodynamic cancer therapy.

Sonodynamic therapy (SDT) has been developed as a promising alternative therapeutic modality for cancer treatment, involving the synergetic application of sonosensitizers and low-intensity ultrasound. However, the antitumor efficacy of SDT is significantly limited due to the poor performance of conventional sonosensitizers in vivo and the constrained tumor microenvironment (TME). Recent breakthroughs in lipid bilayer-based nanovesicles (LBBNs), including multifunctional liposomes, exosomes, and isolated cellular membranes, have brought new insights into the advancement of SDT. Despite their distinct sources and preparation methods, the lipid bilayer structure in common allows them to be functionalized in many comparable ways to serve as ideal nanocarriers against challenges arising from the tumor-specific sonosensitizer delivery and the complicated TME. In this review, we provide a comprehensive summary of the recent advances in LBBN-based SDT, with particular attention on how LBBNs can be engineered to improve the delivery efficiency of sonosensitizers and overcome physical, biological, and immune barriers within the TME for enhanced sonodynamic cancer therapy. We anticipate that this review will offer valuable guidance in the construction of LBBN-based nanosonosensitizers and contribute to the development of advanced strategies for next-generation sonodynamic cancer therapy.