COMPLEX TECHNOLOGICAL AND BIOLOGICAL RESEARCH OF SOLUTIONS FOR PERITONEAL DIALYSIS

Authors

  • Nataliia Hudz Department of Drug Technology and Biopharmacy, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine, http://orcid.org/0000-0002-2240-0852
  • Raisa Korytniuk Department of Pharmaceutical technology and biopharmacy, Shupyk National Medical Academy of postgraduate education, Kyiv, Ukraine,
  • Liliia Vyshnevska Department of Drug Technology, National Pharmaceutical University, Kharkiv, Ukraine
  • Piotr P. Wieczorek Department of Analytical and Ecological Chemistry, University of Opole, Opole, Poland

DOI:

https://doi.org/10.22159/ijap.2018v10i4.24823

Keywords:

Peritoneal dialysis, Prodution, 5-hydroxymethylfurfural, 3, 4-dideoxyglucoson-3-en, Cell viability, Kidneys cells, Vero cells

Abstract

Objective: The purpose of our work was to conduct technological, analytical, and biological investigations and stability studies of peritoneal dialysis (PD) solutions containing glucose and sodium lactate in single-chamber containers.

Methods: Different formulations of PD solutions were prepared and sterilized at a temperature of 121 °C during 15 m. UV-spectrophotometric determination was performed using purified water as a blank. The spectra of the solutions were run in the range of 220 to 400 nm for the identification of an absorption maximum (λmax) and measuring the absorbance at 228-230 nm and λmaxbefore and after heat sterilization. λmax of the most PD solutions after sterilization was found in the range of 273 to 281 nm. The potentiometric determination was done for pH measuring PD solutions before and after sterilization. Alternative analytical procedure of direct argent metric method was employed for fast measuring content of chloride ions. Viability of Vero cells was evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test, neutral red (NR) uptake assay, and sulforhodamine B (SRB) test.

Results: The results showed that the absorbance of the most laboratory batches of PD solutions augments significantly with increasing an autoclave heating time to the sterilization temperature and time of its cooling after sterilization. The longer these parameters, the higher is the absorbance at 228-230 and 273-281 nm indicating 3,4-dideoxyglucoson-3-en (3,4-DGE) and 5-hydroxymethylfurfural (5-HMF) contents, respectively. Glucose degradation is practically absent at short terms of heating and cooling an autoclave while sterilized samples are preserved sterile. Stability studies showed a significant decrease in the absorbance at 228-230 nm during storage with the achievement of a nadir and the following weak increase; an elevation or decrease in the absorption maximum; a substantial decline in the pH of the solution after sterilization and an insignificant pH decrease during storage. The viability of kidney cells was the highest in the SRB test and the lowest one was in the MTT test.

Conclusion: The influence of sterilization regimes on the quality of conventional PD solutions and their stability during storage were studied. The highest cytotoxicity was detected in the MTT test, and the lowest one was done in the SRB test, indicating the largest vulnerability of mitochondria under the influence of PD solutions compared to the membranes permeability, functioning of kidney cell lysosomes and the ability of cells to synthesize proteins. Our studies could be useful in the context of planning development of PD solutions with the purpose of authorization and domestic manufacture of these solutions in low-and-middle-income countries.

Downloads

Download data is not yet available.

Author Biography

Nataliia Hudz, Department of Drug Technology and Biopharmacy, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine,

Drug technology and biopharmaceutics

References

Elsayed AS, Azab AE. Correlation between chronic kidney diseases and hematological data in Sabratha hospital in Libya. Asian J Pharm Clin Res 2017;10:291-6.

Murali M, Sathyanarayana D, Muthusethupathy M. Assessment of quality of life in chronic kidney disease patients using the kidney disease quality of life-short formtm questionnaire in Indian population: a community-based study. Asian J Pharm Clin Res 2015;8:271-4.

Kaur G, Prinja S, Ramachandran R, Malhotra P, Lal Gupta K, Jha V. Cost of hemodialysis in a public sector tertiary hospital of India. Clin Kidney J 2018;1-8. https://doi.org/10.1093/ ckj/sfx152.

Justo P, Sanz AB, Sanz AB, Egido J, Ortiz A. 3,4-dideoxyglucosone-3-ene induces apoptosis in renal tubular epithelial cells. Diabetes 2005;54:2424-9.

Erixon M, Lindén T, Kjellstrand P, Carlsson O, Ernebrant M, Forsbäck G, et al. PD fluids contain high concentrations of cytotoxic GDPs directly after sterilization. Peritoneal Dial Int 2004;4:392-8.

Erixon M, Wieslander A, Lindén T, Carlsson O, Forsbäck G, Svensson E, et al. Take care in how you store your PD fluids: actual temperature determines the balance between reactive and non-reactive GDPs. Peritoneal Dial Int 2005;25:583-90.

Diaz Buxo J, Sawin DA, Himmele R. PD solutions: new and old. Dial Transplant 2011;40:356-61.

Li P, Kit-Chung J, Mcintyre CW. Inflammation and peritoneal dialysis. Semin Nephrol 2017;37 Suppl 1:54-65.

Hanrahan CT. The challenges of heat sterilization of peritoneal dialysis solutions: is there an alternative? Adv Peritoneal Dial 2012;28:126-30.

Kjellstrand P, Erixon M, Wieslander A, Lindén T, Martinson E. Temperature: the single most important factor for degradation of glucose fluids during storage. Peritoneal Dial Int 2004;24:385–91.

Distler L, Georgieva A, Kenkel I, Huppert J, Pischetsrieder M. Structure-and concentration-specific assessment of the physiological reactivity of α-dicarbonyl glucose degradation products in peritoneal dialysis fluids. Chem Res Toxicol 2014;27:1421-30.

Santamaria B, Ucero AC, Reyero A, Selgas R, Ruiz-Ortega M, Catalan M, et al. 3,4-Dideoxyglucosone-3-ene as a mediator of peritoneal demesothelization. Nephrol Dial Transplant 2008;23:3307-15.

Le Poole CY, Welten AG, Ter Wee Pm, Paauw NJ, Djorai AN, Valentijn RM, et al. A dialysis regimen low in glucose and glucose degradation products results in increased cancer antigen 125 and peritoneal activation. Peritoneal Dial Int 2012;32:305-15.

Blake PG, Jain AK, Yochann S. Biocompatible peritoneal dialysis solutions: many questions but few answers. Kidney Int 2013;84:865-6.

Florento L, Matias R, Tuaño E, Santiago K, dela Cruz F, Tuazon A. Comparison of cytotoxic activity of anticancer drugs against various human tumor cell lines using in vitro cell-based approach. Int J Biomed Sci 2012;8 Suppl 1:76-80.

Shabrina M, Suniarti DF, Amir LR, Idrus E. Toxicity analysis of RGD-chitosan from shrimp shell scaffold membranes toward human dental pulp cells. Int J Appl Pharm 2017;9 Suppl 1:13-6.

Nagalakshmik K, Suiathas S. Nanoencapsulation augments release efficacy and glucose tolerance of 14-deoxy, 11,12-didehydroandrographolide loaded polycaprolactone nanoparticles in streptozotocin-nicotinamide induced type 2 diabetes. Int J Appl Pharm 2017;9 Suppl 6:51-3.

Repetto G, del Peso A, Zurita JL. Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat Protoc 2008;3:1125-31.

Bühl A, Zofel P. SPSS Version 10. Einführung in die moderne Datenanalyseunte Windows, 7, uberarbeitete und erweiterte Auflage, DiaSoft; 2005.

British Pharmacopoeia. London; British Pharmacopoeia Commission; 2009.

Тereshkina ОI, Isayeva IV. Investigation of thermal degradation products of glucose in model solutions. Pharm 1991;6:24-8.

Zhang J, Li J, Tang Y, Xue G. Rapid method for the determination of 5-hydroxymethylfurfural and levulinic acid using a double-wavelenght UV spectroscopy. Sci World J 2013;1-6. http://dx.doi.org/10.1155/2013/506329

Sur SV, Arhypova NN, Zvolynska NN. Rezul'tati chetvertogo raunda programmi proffesional'nogo testirovaniya laboratorii v sisteme Gosudarstvennoi inspektsii po kontrolyu kachestva lekarstvennih sredstv MZ Ukraini. 2. Otsenka rezul'tatov opredeleniya soderzhaniya glyukozi i izmereniya rN v testovih obraztsah rastvora glyukozi 5% dlya infuzii. Provizor 2005;8:29-32.

Akter R, Uddin SJ, Tiralongo J, Grice ID, Tiralongo E. A new cytotoxic steroidal glycoalkaloid from the methanol extract of Blumea lacera leaves. J Pharm Pharm Sci 2015;18 Suppl 4:616-33.

Ammerman NC, Beier-Sexton M, Azad AF. Growth and maintenance of vero cell lines. Curr Protoc Microbiol 2008.

Published

07-07-2018

How to Cite

Hudz, N., Korytniuk, R., Vyshnevska, L., & Wieczorek, P. P. (2018). COMPLEX TECHNOLOGICAL AND BIOLOGICAL RESEARCH OF SOLUTIONS FOR PERITONEAL DIALYSIS. International Journal of Applied Pharmaceutics, 10(4), 59–67. https://doi.org/10.22159/ijap.2018v10i4.24823

Issue

Section

Original Article(s)