In silico algorithm for optimization of pharmacokinetic studies of [25Mg2+]porphyrin-fullerene nanoparticles

Fursov VV1,2, Zinchenko DI1, Namestnikova DD2, Kuznetsov DA2,3
About authors

1 Mendeleev University of Chemical Technology, Moscow, Russia

2 Pirogov Russian National Research Medical University, Moscow, Russia

3 Semenov Federal Research Center for Chemical Physics, Moscow, Russia

Correspondence should be addressed: Valentin V. Fursov
Ostrovityanova, 1, Moscow, 117997, Russia; ur.liam@vosrufv

About paper

Funding: the study was funded by by the Ministry of Science and Higher Education of the Russian Federation, grant No. 075-15-2020-792 (Unique identifier RF-190220X0031)

Author contribution: Fursov VV — in silico study supervision, concept, hypothesis, structure, modeling, manuscript writing; Zinchenko DI — modeling, code, manuscript writing; Namestnikova DD — in vivo experiments; Kuznetsov DA — general supervision, data interpretation and analysis, planning of experiments.

Compliance with ethical standards: the study was approved by the ethical review board at the Pirogov Russian National Research Medical University (protocol № 140 of 15 December 2014) and the local committee for surveillance of the maintenance and use of laboratory animals (protocol № 13/2020 of 08 October 2020, protocol № 24/2021 of 10 December 2021).

Received: 2022-07-05 Accepted: 2022-07-18 Published online: 2022-07-22
Fig. 1. A scheme of the five-compartment model of РМС16 pharmacokinetics
Fig. 2. Pharmacokinetic curves built using the model (shown in black) compared with experimental data for the brain, the liver and the heart (Khm = 0.50; Klp = 2; Khp = 0.50; Klm = 6; Khm = 0.50; Ke = 0.077; Kbp = 0.70; Kbm = 0.70; Kism = 0.10; Kisp = 0.10)
Table 1. CZE system calibration: correlation of the internal standard content and optical density values of the identified РМС16 fractions (Rt = 7.0 min)
Note: CZE-analyzed samples comprised S125 aceton-soluble cytosolic pool mixed in a known proportion with NP (1.0–1000.0 ng/mg of the total cytosolic protein). Correlation coefficient r = 0.86; n = 6. NP retention time (effective migration) Rt = 7.0 min. CZE-analyzed sample: S125 aceton-soluble pool mixed in a known proportion with the target compound PMC16–RX (1.0–200.0 ng/mg of protein). Correlation coefficient r = 0.86; n = 6.
Table 2. Permeability of the blood-brain barrier for PMC16-RX and pharmacophore internalization by brain cells
Note: 20 mg of PMC16-RX per 1.0 kg rat body weight intravenously, measured 12 h post-injection.