A lectin mediated delivery system for the intravesical treatment of bladder diseases using poly-(L)-glutamic acid as polymeric backbone.

Abstract

In this study, we present a targeted drug delivery system to improve intravesical therapy of bladder diseases. The drug delivery system consists of wheat germ agglutinin (WGA) to facilitate specific interaction with the surface of bladder cells and α-poly-(L)-glutamic acid (PGA) as polymeric backbone to increase the number of drug molecules per targeting moiety. Additionally, fluorescein cadaverine was coupled to PGA to visualise and track the delivery system. Using 5637 single cells and cell monolayers, the optimised F-PGA-WGA delivery system, with an approximate molecular weight of 670kDa, could convince with its promising cytoadhesive as well as cytoinvasive potential. Using the competitive inhibitor N, N', N″-triacetylchitotriose a specificity of the carbohydrate-mediated interaction between the cell and the delivery system of up to 98% was determined. F-PGA alone did not show any interaction with the cells. Moreover, a high drug loading of 77 molecules of the model drug Dansylcadaverine per backbone was achieved. Microscopic analysis further confirmed binding and uptake of the cytoadhesive polymer even after additional loading with the model drug. Combining the auspicious targeting properties of WGA with the high drug loading possibilities of the backbone might finally lead to an enhanced efficacy when used for intravesical therapy.

• Authors: Christina Apfelthaler, Patrick Gassenbauer, Sandra Weisse, Franz Gabor, Michael Wirth
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 111 Pg. 376-382 (Jan 01 2018) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 29030178 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Biocompatible Materials
• Wheat Germ Agglutinins
• Polyglutamic Acid
• monodansylcadaverine
• Cadaverine

Topics

• Antineoplastic Agents (administration & dosage, chemistry, pharmacokinetics)
• Biocompatible Materials
• Biological Transport
• Cadaverine (administration & dosage, analogs & derivatives, chemistry, pharmacokinetics)
• Cell Line, Tumor
• Drug Delivery Systems
• Humans
• Polyglutamic Acid (chemistry)
• Urinary Bladder Diseases (drug therapy)
• Urothelium (cytology)
• Wheat Germ Agglutinins (chemistry)