Dyshlyuk Lyubov, Sukhikh Stanislav, Noskova Svetlana, Ivanova Svetlana, Prosekov Alexander, Babich Olga
Natural Nutraceutical Biotesting Laboratory, Kemerovo State University, Krasnaya Street 6, 650043 Kemerovo, Russia.
Department of Bionanotechnology, Kemerovo State University, Krasnaya Street 6, 650043 Kemerovo, Russia.
Pharmaceutics. 2021 Mar 13;13(3):383. doi: 10.3390/pharmaceutics13030383.
The kinetics of l-phenylalanine ammonia-lyase (PAL) penetration into the monolayer of liver cells after its release from capsules was studied. The studies showed the absence of the effect of the capsule shell based on plant hydrocolloids on the absorption of l-phenylalanine ammonia-lyase in systems simulating the liver surface. After 120 min of incubation, in all variants of the experiment, from 87.0 to 96.8% of the enzyme penetrates the monolayer of liver cells. The combined analysis of the results concludes that the developed encapsulated form of l-phenylalanine ammonia-lyase is characterized by high efficiency in correcting the disturbed catabolism of phenylalanine in phenylketonuria, which is confirmed by the results of experiments carried out on in vitro model systems. PAL is approved for the treatment of adult patients with phenylketonuria. The encapsulated l-phenylalanine ammonia-lyase form can find therapeutic application in the phenylketonuria treatment after additional in vitro and in vivo studies, in particular, the study of preparation safety indicators. Furthermore, it demonstrated high efficacy in tumor regression and the treatment of tyrosine-related metabolic disorders such as tyrosinemia. Several therapeutically valuable metabolites biosynthesized by PAL via its catalytic action are included in food supplements, antimicrobial peptides, drugs, amino acids, and their derivatives. PAL, with improved pharmacodynamic and pharmacokinetic properties, is a highly effective medical drug.
研究了L-苯丙氨酸解氨酶（PAL）从胶囊释放后渗透到肝细胞单层中的动力学。研究表明，在模拟肝脏表面的系统中，基于植物水胶体的胶囊壳对L-苯丙氨酸解氨酶的吸收没有影响。孵育120分钟后，在所有实验变体中，87.0%至96.8%的酶渗透到肝细胞单层中。对结果的综合分析得出结论，所开发的L-苯丙氨酸解氨酶包封形式在纠正苯丙酮尿症中苯丙氨酸分解代谢紊乱方面具有高效率，这在体外模型系统上进行的实验结果中得到了证实。PAL已被批准用于治疗成年苯丙酮尿症患者。经过额外的体外和体内研究，特别是制剂安全性指标的研究后，包封形式的L-苯丙氨酸解氨酶可在苯丙酮尿症治疗中找到治疗应用。此外，它在肿瘤消退和酪氨酸相关代谢紊乱（如酪氨酸血症）的治疗中显示出高效性。通过PAL的催化作用生物合成的几种具有治疗价值的代谢物包含在食品补充剂、抗菌肽、药物、氨基酸及其衍生物中。具有改善的药效学和药代动力学特性的PAL是一种高效的药物。
