Polyamide-Montmorillonite Nanocomposites as a Drug Delivery System: Preparation, Release of 1,3,4-Oxa(thia)diazoles, and Antimicrobial Activity Nehal Salahuddin, 1 Ahmed Elbarbary, 1 Nanis G. Allam, 2 Ayat F. Hashim 3 1 Department of Chemistry, Faculty of Science, Tanta University, Tanta 31527, Egypt 2 Department of Botany, Faculty of Science, Tanta University, Tanta 31527, Egypt 3 Plant Pathology Research Institute, Agricultural Research Center, Giza, Egypt Correspondence to: N. Salahuddin (E - mail: salahuddin.nehal@yahoo.com) ABSTRACT: New microbicidal polyamides were prepared by the reaction of 5-phenyl-1,3,4,-oxadiazole-2-thiol, 5-phenyl-1,3,4-oxadia- zole-2-amine, and 5-(4-chlorophenyl)21,3,4-thiadiazole-2-thiol with ethyl chloroformate followed by polycondensation with polyoxy- propylenetriamine (Jeffamine T 403 ). The polyamides were modified to yield amine hydrochloride. The intercalation of polyamides into montmorillonite (MMT) was achieved through an ion exchange process between sodium cations in MMT and amine hydro- chloride in the polyamides. The structure of the resulting materials was characterized with elemental analysis, proton nuclear mag- netic resonance, Fourier transform infrared-spectroscopy, X-ray diffraction, thermogravimetric analysis, and transmission electron microscope. The release behavior of 1,3,4-oxa(thia)diazoles was investigated in buffered aqueous solution at different pH values (2.3, 5.8, and 7.4). A slow release was recorded from the nanocomposites whereas; the release reaches almost 90% from polyamides. The in vitro antimicrobial activity of the polyamides and nanocomposites was studied against Gram-negative bacteria, Gram-positive bac- teria, Yeast and the filamentous fungi by well diffusion method. The polymers showed good or moderate antimicrobial activities. However, nanocomposites showed no antimicrobial effect. Furthermore, in vivo study showed that nanocomposites had good antimi- crobial activity. V C 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41177. KEYWORDS: clay; drug delivery systems; nanocomposites; polyamides Received 9 February 2014; accepted 16 June 2014 DOI: 10.1002/app.41177 INTRODUCTION 1,3,4-Oxa(thia)diazoles derivatives exhibit a wide range of biolog- ical activities including antibacterial, 1 antitubercular, 2 vasodiala- tory, 3 antifungal, 4 cytotoxic, 5 anti-inflammatory and analgesic, 6,7 hypolipidemic, 8 anticancer, 9 and ulcerogenic activities. 10 A variety of polymers have been used for medical care including preventing medicine, clinical inspections, and surgical treatments of diseases. 11,12 Numerous polymer biomaterials have been employed for such medical purposes because they have accepta- ble biocompatibility, biodegradability, and absorbability. 13 These polymer materials can act as drug carriers by controlling the release rate of drug initially loaded in application for drug deliv- ery systems. 14 Delivery of drugs dosage for optimal lengths of time will make them more effective and more powerful. Aliphatic polyamide microcapsules were synthesized by the process of interfacial polymerization. 15 This system showed the potential to liberate the incorporated model drug effectively by the process of diffusion through the polyamide microcapsule membrane. Self- regulating reservoir system was prepared with hydrophilic ali- phatic polyamide microcapsules containing succinyl- amidophenyl glucopyranoside insulin (SAPG-insulin) and cross linked concanavalin A (Con A) enclosed in a pouch polymeric membrane. The in vitro data demonstrated rapid diffusion of both glucose and SAPG-insulin across the microcapsule mem- brane with a short lag time for exchange. 16 The efficiency of the hollow polyamide fibers in releasing glycerin trinitrate in order to reduce blood pressure with minimal dermal toxicity was explored. The results showed that the quantity of glycerin trini- trate released per minute within the polyamide hollow fibers was sufficient to reduce blood pressure significantly while it did not show considerable dermal toxicity. 17 Montmorillonite clay mineral (Na-MMT) is one of the smectite group, composed of an alumina octahedral sheet sandwiched Additional Supporting Information may be found in the online version of this article. V C 2014 Wiley Periodicals, Inc. WWW.MATERIALSVIEWS.COM J. APPL. POLYM. SCI. 2014, DOI: 10.1002/APP.41177 41177 (1 of 14)