Abstract
Background: Poly(hydroxyalkanoates) (PHA) have recently attracted increasing attention due to their biodegradability and high biocompatibility, which makes them suitable for the development of new prolong drug formulations.
Objective: A preclinical toxicology study of paclitaxel biopolymer formulation (PBF) (paclitaxel-loaded poly(3- hydroxybutyrate) (PHB) microparticles) was done in order to assess its safety and to forecast side and toxic effects in a clinical study on patients.
Method: PHB microparticles loaded with antitumor cytostatic drug PTX were obtained by spray-drying method using Nano Spray Dryer B-90. The comprehensive study of cytotoxicity (on bone marrow stem cells), acute and chronic toxicity, allergenic and pyrogenic properties, histological investigation (in mice, rats and rabbits) of obtained PBF was carried out.
Results: The acute toxicity study showed that PBF is much less toxic in equivalent PTX-content doses than PTX in conventional formulation when administered intraperitoneally to mice and rats. However, the chronic toxicity study showed that at intraperitoneal administration PBF has distinct cumulative properties and toxic effects that prevent PBF from clinical testing in current composition.
Conclusion: Thus, the PBF as a prolong drug needs to correct its parameters for further drug formulation development.
Keywords: Anticancer agent, paclitaxel, poly(3-hydroxybutyrate), toxicity, allergenicity, pyrogenicity, adaptive therapy.
Anti-Cancer Agents in Medicinal Chemistry
Title:Preclinical Toxicity of Paclitaxel Biopolymer Formulation
Volume: 17 Issue: 12
Author(s): Nadezhda P. Ermakova, Anton P. Bonartsev*, Anton L. Zernov, Olga I. Konyaeva, Natalia Y. Kulbachevskaya, Irina B. Merkulova, Tatiana V. Abramovac, Vera A. Chaley, Irina I. Zharkova, Sergey G. Yakovlev, Vera. L. Myshkina, Tatiana K. Mahina, Garina A. Bonartseva, Konstantin V. Shaitan and Vladimir M. Bukhman
Affiliation:
- Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow,Russian Federation
Keywords: Anticancer agent, paclitaxel, poly(3-hydroxybutyrate), toxicity, allergenicity, pyrogenicity, adaptive therapy.
Abstract: Background: Poly(hydroxyalkanoates) (PHA) have recently attracted increasing attention due to their biodegradability and high biocompatibility, which makes them suitable for the development of new prolong drug formulations.
Objective: A preclinical toxicology study of paclitaxel biopolymer formulation (PBF) (paclitaxel-loaded poly(3- hydroxybutyrate) (PHB) microparticles) was done in order to assess its safety and to forecast side and toxic effects in a clinical study on patients.
Method: PHB microparticles loaded with antitumor cytostatic drug PTX were obtained by spray-drying method using Nano Spray Dryer B-90. The comprehensive study of cytotoxicity (on bone marrow stem cells), acute and chronic toxicity, allergenic and pyrogenic properties, histological investigation (in mice, rats and rabbits) of obtained PBF was carried out.
Results: The acute toxicity study showed that PBF is much less toxic in equivalent PTX-content doses than PTX in conventional formulation when administered intraperitoneally to mice and rats. However, the chronic toxicity study showed that at intraperitoneal administration PBF has distinct cumulative properties and toxic effects that prevent PBF from clinical testing in current composition.
Conclusion: Thus, the PBF as a prolong drug needs to correct its parameters for further drug formulation development.
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Cite this article as:
Ermakova P. Nadezhda, Bonartsev P. Anton*, Zernov L. Anton, Konyaeva I. Olga, Kulbachevskaya Y. Natalia, Merkulova B. Irina, Abramovac V. Tatiana, Chaley A. Vera, Zharkova I. Irina, Yakovlev G. Sergey, Myshkina L. Vera. , Mahina K. Tatiana, Bonartseva A. Garina, Shaitan V. Konstantin and Bukhman M. Vladimir, Preclinical Toxicity of Paclitaxel Biopolymer Formulation, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (12) . https://dx.doi.org/10.2174/1871520616666160817104529
DOI https://dx.doi.org/10.2174/1871520616666160817104529 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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