Characteristics of novel polymer based on pseudo-polyamino acids GluLa-DPG-PEG600: binding of albumin, biocompatibility, biodistribution and potential crossing the blood-brain barrier in rats

B. O. Chekh Chekh, M. V. Ferens, D. D. Ostapiv, V. Y. Samaryk, S. M. Varvarenko, V. V. Vlizlo
2017 Ukrainian Biochemical Journal  
the aim of our work was to study biological properties of the polymer based on pseudo-polyamino acids GluLa-DPG-PEG600, its ability to bind albumin, as well as its localization in rat body and influence on physio logical and functional state of rat kidneys and liver. We have found the ability of Glula-DpG-peG600 to bind bovine serum albumin (BSa) using electrophoresis in 5% polyacrylamide gel. Structural and functional state of the liver and kidneys of rats after injections of polymer were
more » ... f polymer were investigated by histological analysis of organs and determination the activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase and content of cholesterol and creatinine in blood. Our results showed little toxic effect of GluLa-DPG-PEG600 on rat body. Using fluorescent microscopy we have studied polymer in complex with BSa distribution in rat body: after intravenous injection polymer are localized in kidneys and spleen, and after intramuscular -in liver and brain. It has been shown that polymer passed through the blood-brain barrier and are localized in the immune organ -spleen, indicating Glula-DpG-peG600 as a potential drug transporter. k e y w o r d s: polymer based on pseudo-polyamino acids, drug transporter, adjuvant, liver and kidneys of rats. N owadays, one of the main task for phar macy is development a novel polymeric compounds for drug delivery and other biomedical purposes [1]. It has been developed poly mers based on amino acids with good biocompati bility like hydrogel based on poly γ-glutamic acid (γ-PGA) and ε-polylysine (ε-PL) or able to adsorb rare earth elements like sodium alginate hydrogel linked with poly-γ-glutamate [2, 3]. Scientists also developed specific polymers for drug delivery, for example lysinebased hydrogels for the oral delivery which are pHsensitive or safe detoxifying agent like poly(γ-glutamic acid) [4, 5] . We develop and research polymers based on pseudopolyamino acids which, like polymers based on amino acids, have good bio compatibility but are more stable for degradation. Pseudo-polyamino acids -class of polymeric compounds based on natural amino acids. Their structure doesn't contain peptide bonds, ones can be changed to urethane, ester, anhydrite and other chemical bonds [6] . Drug delivery systems based on pseudopolyamino acids with ester bonds are re spectable for research and developing. Pseudo-poly amino acids based on glycine, asparagine, arginine and lysine in complex with lactic acid are biodegra dable and have advanced cell adhesion [7] [8] [9] . Pseu dopolyamino acids based on tyrosine in complexes with ZnO can be used in anticancer therapy [10, 11] . The main advantages of this class of polymers as drug transporters are their biodegradability and prolonged time of degradation that correlates with releasing of drugs active components (for example, polymers based on glycine and lactic acid are de composed for about 10 weeks) [7, 8] . Polymer Glu La-DPG-PEG600 based on glutamic acid with ester bonds was developed. Therefore, the main purpose
doi:10.15407/ubj89.04.013 fatcat:mm4uyzgozjbb5cwnxejcsmr4vq