Extracellular vesicles (EVs) hold great promise for clinical application as new diagnostic and therapeutic modalities. This paper describes major GMP-based upstream and downstream manufacturing processes for EV large-scale production, also focusing on post-processing technologies such as surface bioengineering and uploading studies to yield novel EV-based diagnostics and advanced therapy medicinal products. This paper also focuses on the quality, safety, and efficacy issues of the bioengineered EV drug candidates before first-in-human studies. Because clinical trials involving extracellular vesicles are on the global rise, this paper encompasses different clinical studies registered on clinical-trial register platforms, with varying levels of advancement, highlighting the growing interest in EV-related clinical programs. Navigating the regulatory affairs of EVs poses real challenges, and obtaining marketing authorization for EV-based medicines remains complex due to the lack of specific regulatory guidelines for such novel products. This paper discusses the state-of-the-art regulatory knowledge to date on EV-based diagnostics and medicinal products, highlighting further research and global regulatory needs for the safe and reliable implementation of bioengineered EVs as diagnostic and therapeutic tools in clinical settings. Post-marketing pharmacovigilance for EV-based medicinal products is also presented, mainly addressing such topics as risk assessment and risk management.

The aim of the present research was to examine the effect of conjugated linoleic acids (CLA) supplementation on the activity of enzymes that take part in the synthesis of arachidonic acid (AA) and also to investigate the relation between their activity and the neoplastic process. The enzyme activities were established indirectly, because their measure was the amount of AA formed in vitro, being developed from linoleic acid as determined in liver microsomes of Spraque-Dawley rats. In addition, the indices of Δ⁶-desaturase (D6D) and Δ⁵-desaturase (D5D) were determined. To this aim, the method of high per-formance liquid chromatography with UV/VIS detection was used. Between the examined groups, statistically significant differences were observed in the activities of enzymes as well as D6D. The carcinogenic agent applied (DMBA) was found to significantly increase the activity of the examined enzymes. Negative correlation was found between the activities of desaturases and CLA supplementation, whereas the activity of those enzymes was a little higher in the group of rats with chemically induced cancer process. The neoplastic process has a stimulating effect on the activity of D6D. The decrease of D6D activity, resulting from the presence of CLA in the animals' diet, may confirm the anticancer properties of these isomers.

The present study aimed to assess the levels of 98 multi-class pharmaceuticals including cardiovascular drugs, antidepressants, hypnotics, antibiotics, and sulfonamides occurring in the muscle tissue of fish caught in the Baltic Sea. The following fish species were collected: perch (Perca fluviatilis); flounder (Platichthys flesus); turbot (Scophthalmus maximus); plaice (Pleuronectes platessa); cod (Gadus morhua callarias); bream (Abramis brama); crucian (Carassius carassius). Additionally, in the examined fish muscle the levels of heavy metals and trace elements were determined (As; Ag; Au; Ba; Cd; Co; Cr; Cu; Hg; Li; Mo; Ni; Pb; Sb; Se; Sn; Tl; V) as well as the levels of cholesterol and its 5 derivatives (7-ketocholesterol; 7α-hydroxycholesterol; 7β-hydroxycholesterol; 5β,6β-epoxy-cholesterol; 5α,6α-epoxycholesterol). In the performed studies 11 out of 98 examined pharmaceuticals were detected in fish muscle. The levels of pharmaceuticals in fish muscle varied depending on the species. In the tissues of bream and crucian, no pharmaceuticals were found. Mercury, lead and arsenic were detected in the muscles of all examined fish. Based on the hazard factor for Hg, Pb, Cd, Ni (target hazard quotient, THQ < 1), it was found that the consumption of the studied fish does not constitute a health risk. However, the THQ for As remained >1 indicated possible risk from those metals. In the examined fish muscle the total cholesterol oxidation products (COPs) level of oxysterols were, respectively: 6.90 (cod) μg/g–4.18 μg/g (perch), which corresponded to 0.7–1.5% of cholesterol. The main COPs evaluated were 7-ketocholesterol (0.78 ± 0.14–1.79 ± 0.06 μg/g), 7β-hydroxycholesterol (0.50 ± 0.04–3.20 ± 2.95 μg/g) and 5β,6β-epoxycholesterol (0.66 ± 0.03–1.53 ± 0.66 μg/g). The assessment of health hazards due to contaminations is necessary, which may help to introduce national legislation and global standards aimed at reducing or even eliminating the exposure to contaminants.

The purpose of this work was to evaluate the effect of the nanosized or microsized zinc (Zn) particles on fatty acid profile, enzyme activity and the level of cholesterol, squalene and oxysterols in rats with breast cancer. Rats (female, n = 24) were divided into the following groups: control, and two test groups, whose diets were enriched with either Zn microparticles (342 nm) or Zn nanoparticles (99 nm). All rats were treated twice with the carcinogenic agent; 7,12-dimethylbenz[a]anthracene. In rats whose diet was enriched with zinc (especially in the form of nanoparticles), the number and sizes of tumors were lower. Diet supplementation also significantly reduced the cholesterol (p = 0.027) and COPs (cholesterol oxidation products) levels (p = 0.011) in rats serum. Enriching the diet with Zn microparticles decreased the Δ6-desaturase activity (p < 0.001). Zn influences fatty acids’ profile in rats’ serum as well as inhibiting desaturating enzymes. A reduced amount of pro-inflammatory arachidonic acid derivatives may be the expected effect.