Bioresponsive Hybrid Nanofibers Enable Controlled Drug Delivery through Glass Transition Switching at Physiological Temperature

Abstract

To avoid excessive usage of antibiotics and antimicrobial agents, smart wound dressings permitting controlled drug release for treatment of bacterial infections are highly desired. In search of a sensitive stimulus to activate drug release under physiological conditions, we found that the glass transition temperature (T g ) of a polymer or polymer blend can be an ideal parameter because a thermal stimulus can regulate drug release at the physiological temperature of 37 °C. A well-tuned T g for a controlled drug release from fibers at 37 °C was achieved by varying the blending ratio of Eudragit® RS 100 and poly(methyl methacrylate). Octenidine, an antimicrobial agent often used in wound treatment, was encapsulated into the polymer blend during the electrospinning process and evaluated for its controlled release based on modulation of temperature. The thermal switch of the nanofibrous membranes can be turned "on" at physiological temperature (37 °C) and "off" at room temperature (25 °C), conferring a controlled release of octenidine. It was found that octenidine can be released in an amount at least 8.5 times higher (25 mg•L −1 ) during the "on" stage compared to the "off" stage after 24 h, which was regulated by the wet T g (34.8−36.5 °C). The "on"/"off" switch for controlled drug release can moreover be repeated at least 5 times. Furthermore, the fabricated nanofibrous membranes displayed a distinctive antibacterial activity, causing a log3 reduction of the viable cells for both Gram negative and positive pathogens at 37 °C, when the thermal switch was "on". This study forms the groundwork for a treatment concept where no external stimulus is needed for the release of antimicrobials at physiological conditions, and will help reduce the overuse of antibiotics by allowing controlled drug release.

Advanced antifouling and antibacterial hydrogels enabled by controlled thermo-responses of a biocompatible polymer composite

“…The cumulative release of OCT from Hydrogel 4:6, 5:5, 6:4, and 7:3 was assessed as reported [4] by UVvis in PBS buffer at 30 °C and 37 °C, respectively, to simulate the temperatures of normal skin and infected wounds (Figure 2a and Tables S1&S2). Hydrogel 4:6 allowed an OCT release at 30 °C of 4.84 ± 0.34 and 5.07 ± 0.44 mg•L -1, respectively, for a release time of 120 and 600 minutes, and at 37 °C of 5.12 ± 0.42 and 5.24 ± 0.77 mg•L -1 .…”

Comprehensive Characterization of PVDF Nanofibers at Macro- and Nanolevel

“…Nowadays, nanofibers development, production and their properties characterization are of high interest among scientists [ 1 , 2 , 3 , 4 , 5 , 6 ], health doctors [ 4 , 7 , 8 , 9 ], and even between general public thanks to coronavirus pandemic situation (causing COVID-19 illness) and use of nanofibers in face masks [ 10 , 11 ] to prevent health of each individual. Another great use of fibers can be for energy harvesting or as sensors from fiber mats as the fibers are from piezoelectric material.…”

Nanofiber Carriers of Therapeutic Load: Current Trends

“…Such a decrease in Tg can result in increased drug release and can serve as a base for design of stimuli-sensitive drug release under physiological conditions. An Eudragit ® RS 100, a copolymer of poly(ethyl acrylate, methyl-methacrylate and chlorotrimethyl-ammonioethyl methacrylate) and poly(methylmethacrylate) (PMMA) blend was tuned to release loaded molecules as a response to thermal stimuli when nanofiber membranes were exposed to physiological temperature [ 104 , 105 ]. Glass transition temperature of 34.8–36.5 °C in water environment (“wet” Tg) enabled the release of antimicrobial Octenidine that was 8.5-times higher in the “on” state than under the “off” conditions (25 °C), and could be repeated over five cycles [ 104 ].…”

“…An Eudragit ® RS 100, a copolymer of poly(ethyl acrylate, methyl-methacrylate and chlorotrimethyl-ammonioethyl methacrylate) and poly(methylmethacrylate) (PMMA) blend was tuned to release loaded molecules as a response to thermal stimuli when nanofiber membranes were exposed to physiological temperature [ 104 , 105 ]. Glass transition temperature of 34.8–36.5 °C in water environment (“wet” Tg) enabled the release of antimicrobial Octenidine that was 8.5-times higher in the “on” state than under the “off” conditions (25 °C), and could be repeated over five cycles [ 104 ]. In the infected areas where the wound temperature is higher than the temperature of surrounding healthy skin, such tunable nanofiber wound dressings are ideal depots for on-demand release of therapeutic agents for wound healing.…”