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Targeted delivery of doxorubicin still poses a challenge with regards to the quantities reaching the target site as well as the specificity of the uptake. In the present approach, two colloidal nanocarrier systems, NanoCore-6.4 and NanoCore-7.4, loaded with doxorubicin and characterized by different drug release behaviors were evaluated in vitro and in vivo. The nanoparticles utilize a specific surface design to modulate the lipid corona by attracting blood-borne apolipoproteins involved in the endogenous transport of chylomicrons across the blood–brain barrier. When applying this strategy, the fine balance between drug release and carrier accumulation is responsible for targeted delivery. Drug release experiments in an aqueous medium resulted in a difference in drug release of approximately 20%, while a 10% difference was found in human serum. This difference affected the partitioning of doxorubicin in human blood and was reflected by the outcome of the pharmacokinetic study in rats. For the fast-releasing formulation NanoCore-6.4, the AUC0→1h was significantly lower (2999.1 ng × h/mL) than the one of NanoCore-7.4 (3589.5 ng × h/mL). A compartmental analysis using the physiologically-based nanocarrier biopharmaceutics model indicated a significant difference in the release behavior and targeting capability. A fraction of approximately 7.310–7.615% of NanoCore-7.4 was available for drug targeting, while for NanoCore-6.4 only 5.740–6.057% of the injected doxorubicin was accumulated. Although the targeting capabilities indicate bioequivalent behavior, they provide evidence for the quality-by-design approach followed in formulation development.

Co-encapsulation of abiraterone acetate (AbrA) and docetaxel (Dtx) in polymeric nanoparticles as novel prototypes for prostate cancer treatment combining hormonal and chemotherapy was designed. Nanoparticles (NPs) composed of poly(DL-lactide-co-glycolide) (PLGA) were prepared by singleemulsion solvent evaporation technique and characterized in terms of morphology with atomic force microscopy and transmission electron microscopy. HPLC method for simultaneous determination of AbrA and Dtx encapsulation efficacy was developed. Also differential scanning calorimetry and Fouriertransform infrared spectroscopy were provided. To study the effectiveness of cellular internalization and distribution of NPs with AbrA and Dtx co-encapsulation (NP-AbrA/Dtx), a fluorescence microscopy was utilized. NPs prepared had size 256.3 AE9.4 nm and zeta potential −18.4 AE1.4 mV. Encapsulation efficacy for AbrA was 68.7% and for Dtx was 74.3%. NPs were able to control the AbrA and Dtx release within 24 h. The mathematical model of drug release was performed. The results obtained from confocal microscopy showed the effective accumulation of the NP-AbrA/Dtx in the cytoplasm of cells. Synthesized NPs possessed satisfactory parameters and a biphasic release profile, proceeding by the Fick diffusion mechanism, which provide prolonged release of the drugs and maintenance of their concentration. It was shown that NPs loaded with AbrA and Dtx exhibited a high cytotoxic activity on the LNCaP cell line, similar to the combination of free drugs of AbrA and Dtx, but in contrast to the combination of substances, had a synergistic mechanism of action. Our findings support the potential use of developed NPs in further in vivo studies.How to cite this article: Sokol MB, Nikolskaya ED, Yabbarov NG, Zenin VA, Faustova MR, Belov AV, Zhunina OA, Mollaev MD, Zabolotsky AI, Tereshchenko OG, Severin ES. 2019. Development of novel PLGA nanoparticles with co-encapsulation of docetaxel and abiraterone acetate for a highly efficient delivery into tumor cells. J Biomed Mater Res Part B 2019:107B:1150-1158.

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The paper is focused on the regularities and character of the response of the regional landscapes of the Angara–Lena Plateau to variations in the global climate system during the Holocene. They were revealed by integrated studies of four peat bogs of the plateau—an important area for the understanding of the environmental dynamics in the entire Baikal region. Age models for the records obtained were provided by 16 radiocarbon dates. A spatiotemporal correlation of spore–pollen indices with the trend of δ18O records from the global stratotypes was used to find out the possible causes of changes in the landscapes and climate of the Angara–Lena Plateau in the context of past changes in the global climate system. The plateau environment showed a dramatically varying response to global climate variations in the Middle–Late Holocene. Moreover, the observed intervals of reorganization in the regional environment took place in a quasi-millennial regime, in accordance with global climate rearrangement. However, not all the studied regions of the Angara–Lena Plateau exhibited a synchronous or analogous response to global environment change. This emphasizes the complicated character of regional climate manifestations in the Holocene and necessitates the use of paleogeographical data from a wider range of territories.