Table 1.
Toxicity/safety evaluation results of representative microalgae-based delivery systems.
| Study topic | Microalgae species/system | Model | Dose/Exposure | Assay | Results | Reference |
|---|---|---|---|---|---|---|
| Microalgal biohybrid microrobots in IBD therapy | Hp@CS-PNAs@PAA | In vivo biodistribution and toxicity: BALB/c mice | Oral administration of Hp@CS-PNAs@PAA (Hp: 5 mg/mL; PNAs: 4.5 mg/mL) | Fluorescence imaging and histological analysis (H&E staining) | No detectable damage to major organs (heart, liver, spleen, lungs, kidneys) after treatment with Hp@CS-PNAs@PAA. | [41] |
| Microalgal biomass for oral intestinal disease treatment | SP@Curcumin | Cytotoxicity: intestinal epithelial cells (IEC-6) | Incubated with different concentrations of SP, curcumin, and SP@Curcumin for 24 h | MTT assay | SP@Curcumin exhibited significantly lower cytotoxicity compared to free curcumin. For example, at a concentration of 50 μg/ml SP, SP@Curcumin showed cell viability of about 80 %, while free curcumin showed cell viability of less than 60 %. | [30] |
| Biosafety: Healthy female Balb/c mice (6 weeks old) | Intragastric administration for 30 days | Blood routine and blood biochemistry parameters, H&E staining of major organs (heart, liver, spleen, kidney, lung) | No significant differences in blood parameters or histological damage observed compared to control group. | |||
| pH-responsive microalgal hydrogels for oral insulin delivery | CV@INS@ALG | Cytotoxicity: IEC-6 | Various concentrations (6.25−200 μg/mL) | MTT assay | Cell viability: >90 % at all tested concentrations (6.25−200 μg/mL). | [95] |
| Long-term in vivo biosafety: C57BL/6J mice | Daily oral administration for 30 days (CV = 366.5 mg/kg, insulin = 20 IU/kg) | Histology and blood biochemistry tests | No obvious pathological changes or abnormal inflammation in gastrointestinal tract and other major organs. | |||
| Biodistribution and degradation: BALB/c nude mice | Single oral administration (CV = 366.5 mg/kg, insulin = 20 IU/kg) | Fluorescence imaging, TEM/SEM of gastrointestinal contents | Fluorescence signal detected in upper abdomen at 0.5 h, spread to lower abdomen by 2 h, and almost undetectable at 8 h. | |||
| Microalgal cross-scale delivery for GBM treatment | Diatom microrobots (DMs) | Cytotoxicity: human brain astroblastoma cells (U87 cells) | Incubated with concentrations ranging from 0.01 to 1.5 mg/mL of DMs | CCK-8 assay | negligible cytotoxicity at concentrations up to 1.5 mg/mL (cell viability >50 %). | [111] |
| Euglena hydrogel system for gout | Eug-Col@Fucar | Biosafety evaluation: male KM mice (4 weeks) | Daily oral administration for 15 days: Eug (4 mg/mL), Col (100 μg/mL), Fucar (10 mg/mL/7.5 mg/mL), Eug-Col@Fucar (4 mg/mL, 100 μg/mL, 10 mg/mL/7.5 mg/mL) | Blood routine analysis, blood chemistry analysis, histological evaluation (H&E staining) of major organs | No significant differences in blood routine and biochemical parameters between treatment groups and control group. No detectable damage or histopathological lesions in heart, spleen, lungs, or kidneys. | [145] |
| Side effect assessment: male KM mice (4 weeks) | 17 days of treatment: Control (PBS 10 mg/kg), Model (PBS 10 mg/kg), Eug (4 mg/mL), Col (100 μg/mL), Fucar (10 mg/mL/7.5 mg/mL), Eug-Col@Fucar (4 mg/mL, 100 μg/mL, 10 mg/mL/7.5 mg/mL) | Organ weight ratio to body weight, histological analysis (H&E staining) of stomach and liver, measurement of colon length, histological analysis (H&E staining) of colon | Eug-Col@Fucar group: Normal organ indices, restored colon length (10.675 ± 0.998 cm), mitigated gastrointestinal and hepatic damage. | |||
| Light-driven microalgae micromotor for PDT | Drug-loaded Chlamydomonas reinhardtii micromotor (R-motor) | In vivo biosafety: Balb/c mice | Single intravenous injection of R-motor (4 × 109 kg−1 of Chlamydomonas reinhardtii) | Body weight monitoring, survival rate, hematology tests (PLT, AST, ALT, HGB, WBC, Neu, UREA, UA), histological analysis (H&E staining) | No significant weight loss was observed in treated mice; Only one mortality was recorded in both the algae-alone group and the control group over the 10-day treatment period; No significant deviations in blood indices compared to the untreated tumor-bearing group; No discernible damage was observed in major organs | [29] |
Note: ALG, sodium alginate; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CV, Chlorella vulgaris; CS, chitosan; Col, colchicine; Eug, Euglena; Fucar, fucoidan-carrageenan complex; GBM, glioblastoma; H&E, hematoxylin and eosin; HGB, hemoglobin; Hp, Haematococcus pluvialis; INS, insulin; IU, international unit; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Neu, neutrophils; PDT, photodynamic therapy; PAA, poly(acrylic acid); PNAs, platinum nanoparticle assemblies; PLT, platelet count; SP, Spirulina platensis; UA, uric acid; UREA, urea; WBC, white blood cell count.