among others, [8][9][10] for the release of encapsulated drug from monolithic fibers or core-shell fibers, [11][12][13] relying in general on solute diffusion, polymeric matrix swelling, and degradation. Alternatively, electrospun fibers were designed to achieve controlled release upon specific stimuli such as pH when using polyelectrolytes, [14,15] or thermal when using thermo-responsive polymers (TPs) with a lower critical solution temperature (LCST) such as poly(N-isopropylacrylamide) (PNIPAAm) with a phase transition temperature at around 32 °C. [16] In this work, we demonstrate a temperature-controlled release of model nanoparticles from pores of potential transdermal nonwoven patch. The transdermal delivery of drugs and bioactive molecules has lot of implications not only for the local skin disease therapy but also for systemic delivery of drugs. [17] Till now, nano-sized carrier systems such as micelles, polymeric nanoparticles, or liposomes are the main skin-delivery systems to facilitate drug delivery by topical application. [18,19] Nano-carriers may facilitate transportation and/ or allow creating depots of drugs in the skin for a sustained or stimuli-induced release using external triggers based on temperature, pH, light, magnetic field, ultrasound, or electrical. [18,20] The patch in our work is made of a thermoresponsive electrospun fibrous matrix with a LCST-type phase transition temperature at 45 °C for a controlled release above the body temperature, which is not possible with PNIPAAm. Nanoparticles are encapsulated in the inter-fiber pores surrounded by a medium. When raising the ambient temperature above the LCST, the fibrous matrix shrink and as a result the encapsulated medium with the suspended particles is released to the immediate environment where the fibrous patch is applied onto the skin surface (Scheme 1).At first, we demonstrate the synthesis, characterization, and preparation of electrospun fibers of an LCST-type poly(methylacrylamide-co-N-tert-butylacrylamide-co-4-acryloylbenzophenone) P(MAAm-NtbAAm-ABP) copolymer. The copolymer was successfully electrospun to form a nano-fibrous matrix, which exhibits thermo-initiated, LCST-based shrinkage in aqueous media. Then, for the demonstration of the temperature-triggered-release, the fibrous matrix was uploaded at room temperature with nano-carriers (fluorescently labeled carboxylated latex nanoparticles, 200 nm in diameter) and in situ release while heating was monitored using real-time fluorescence microscopy. The thermo-responsive fibrous matrix demonstrated controlled nano-carriers release due to rapid and reversible swelling and shrinking, in aqueous media.
Nonwoven DepotsA novel thermoresponsive fibrous matrix as controlled release depots upon heating is described. The matrix is composed of electrospun fibers of a lower critical solution temperature (LCST)-type poly(methacrylamide-co-N-tert-butylacrylamide-co-4-acryloylbenzophenone) P(MAAm-NtbAAm-ABP) copolymer. Spherical particles, simulating depots of drugs, are embedded with liquid...