Zahra Toutou

Delivering hydrophobic active pharmaceutical ingredients remains a major challenge due to poor aqueous solubility, limited bioavailability, and chemical instability. Drug‐in‐cyclodextrin‐in‐liposome (DCL) technology combines cyclodextrin inclusion complexation with liposomal encapsulation to address these limitations. In this hybrid approach, the hydrophobic drug is first incorporated into the apolar cyclodextrin cavity, and the resulting complex is subsequently encapsulated within the aqueous compartment of liposomes. This review provides a comprehensive, data‐driven analysis of DCL technology, covering its conceptual development, cyclodextrin properties, lipid composition, vesicle architecture, and preparation methods. Quantitative parameters, including encapsulation efficiency, particle size, zeta potential, and drug release, are compared with conventional liposomes and cyclodextrin complexes. DCL systems demonstrated 2 to 11 fold higher encapsulation efficiency than conventional liposomes, together with sustained release, improved vesicle stability, and enhanced protection of labile drugs against degradation. Preclinical evidence indicates potential therapeutic benefits, although in vivo validation remains limited. Molecular docking and molecular dynamics further provide mechanistic insights into drug–cyclodextrin and cyclodextrin–membrane interactions. Emerging strategies include surface modification, stimuli‐responsive systems, dual‐drug loading, green manufacturing, and computational design, supporting the future clinical translation of DCL technology.

Background: Coffee capsules are increasingly consumed worldwide and represent a complex source of bioactive compounds, notably caffeine (stimulant), caffeic acid (antioxidant), and acrylamide (toxicant). Aims: The objectives of this investigation were twofold: (i) assess total phenolic content (TPC), antioxidant capacity, pH, and browning index, across seven commercial capsule products (comprising six Algerian brands widely consumed locally and one European comparator with undisclosed blend/roast); and (ii) to develop and validate an HPLC – Diode Array Detection (DAD) procedure for the simultaneous determination of caffeine, caffeic acid, and acrylamide , serving as joint indicators of product quality and safety. Methods: The TPC was determined employing the Folin–Ciocalteu method, while antioxidant activity was assessed by the DPPH radical scavenging assay. The simultaneous quantification of caffeine, caffeic acid, and acrylamide were performed by a validated HPLC – DAD procedure in accordance with International Council for Harmonization (ICH) guidelines. Results: The resulting coffee brews exhibited pH values ranging from 5.64 to 6.25 and browning indices between 0.280 and 0.482, reflecting roasting differences. Despite a modest TPC (0.9 to 2 mg GAE/g), the antioxidant activity was high, (up to 95.3% inhibition DPPH). Caffeine was consistently detected (0.05 – 0.33 mg/25 mL), confirming its stimulant role. Caffeic acid was present in lower concentrations (0.001 – 0.14 mg/25 mL), contributed to the antioxidant potential. In contrast, acrylamide was detected in all analyzed samples ranging from 4.75 to 28.15 µg/25 mL). On a dry coffee basis, these concentrations correspond to 458 – 4023 µg/kg. A majority of the capsules yielded levels that exceed the European Commission’s benchmark of 400 µg/kg for roasted coffee, thereby underscoring consumer-relevant exposure level and raising toxicological concern. Conclusions: Coffee capsule brews demonstrated notable antioxidant capacity despite modest TPC, with caffeine ubiquitous and caffeic acid detectable. The presence of acrylamide was confirmed in all samples at levels that warrant monitoring. The validated HPLC–DAD workflow enables the simultaneous determination of these markers and offers a robust basis for integrated quality control and risk assessment in encapsulated coffee products. Keywords: Coffee capsule; Antioxidant activity; High-Performance Liquid Chromatography (HPLC); Caffeic acid; Caffeine; Acrylamide.

Propolis, a bee product, is renowned globally for its diverse pharmacological activities attributed to its phenolic compounds, flavonoids, and terpenes. This study aims to identify the chemical compounds in Algerian raw propolis and evaluate the protective potential of its inclusion complex. Gas chromatography–mass spectrometry (GC/MS), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) were used for chemical characterization. Additionally, molecular docking against SARS‐COVID‐2 main proteases and ADMET profiling were conducted. The analysis revealed α‐pinene (25.29%–11.04%) and limonene (22.46%–12.88%) as the major components in raw propolis and its complex. DSC/TGA analysis demonstrated the protective effect of encapsulated molecules, with limonene and α‐pinene showing high activity against SARS‐COVID‐2 main proteases 7N5Z, 6LU7, and 7E6L, with docking scores of −5.71, −5.61, and −5.10 kcal/mol, respectively. This study highlights the potential of propolis constituents as drug candidates against the SARS‐COVID‐2 pandemic.