Two-Photon Polymerisation 3D Printing of Microneedle Array Templates with Versatile Designs: Application in the Development of Polymeric Drug Delivery Systems.

PURPOSE: To apply a simple and flexible manufacturing technique, two-photon polymerisation (2PP), to the fabrication of microneedle (MN) array templates with high precision and low cost in a short time. METHODS: Seven different MN array templates were produced by 2PP 3D printing, varying needle height (900-1300 µm), shape (conical, pyramidal, cross-shaped and with pedestal), base width (300-500 µm) and interspacing (100-500 µm). Silicone MN array moulds were fabricated from these templates and used to produce dissolving and hydrogel-forming MN arrays. These polymeric MN arrays were evaluated for their insertion in skin models and their ability to deliver model drugs (cabotegravir sodium and ibuprofen sodium) to viable layers of the skin (ex vivo and in vitro) for subsequent controlled release and/or absorption. RESULTS: The various templates obtained with 2PP 3D printing allowed the reproducible fabrication of multiple MN array moulds. The polymeric MN arrays produced were efficiently inserted into two different skin models, with sharp conical and pyramidal needles showing the highest insertion depth values (64-90% of needle height). These results correlated generally with ex vivo and in vitro drug delivery results, where the same designs showed higher drug delivery rates after 24 h of application. CONCLUSION: This work highlights the benefits of using 2PP 3D printing to prototype variable MN array designs in a simple and reproducible manner, for their application in drug delivery.

Bioinspired Multiresonant Acoustic Devices Based on Electrospun Piezoelectric Polymeric Nanofibers.

Cochlear hair cells are critical for the conversion of acoustic into electrical signals and their dysfunction is a primary cause of acquired hearing impairments, which worsen with aging. Piezoelectric materials can reproduce the acoustic-electrical transduction properties of the cochlea and represent promising candidates for future cochlear prostheses. The majority of piezoelectric hearing devices so far developed are based on thin films, which have not managed to simultaneously provide the desired flexibility, high sensitivity, wide frequency selectivity, and biocompatibility. To overcome these issues, we hypothesized that fibrous membranes made up of polymeric piezoelectric biocompatible nanofibers could be employed to mimic the function of the basilar membrane, by selectively vibrating in response to different frequencies of sound and transmitting the resulting electrical impulses to the vestibulocochlear nerve. In this study, poly(vinylidene fluoride-trifluoroethylene) piezoelectric nanofiber-based acoustic circular sensors were designed and fabricated using the electrospinning technique. The performance of the sensors was investigated with particular focus on the identification of the resonance frequencies and acoustic-electrical conversion in fibrous membrane with different size and fiber orientation. The voltage output (1-17 mV) varied in the range of low resonance frequency (100-400 Hz) depending on the diameter of the macroscale sensors and alignment of the fibers. The devices developed can be regarded as a proof-of-concept demonstrating the possibility of using piezoelectric fibers to convert acoustic waves into electrical signals, through possible synergistic effects of piezoelectricity and triboelectricity. The study has paved the way for the development of self-powered nanofibrous implantable auditory sensors.

Ochratoxin A levels in spices and dried nuts consumed in Tunisia.

A total of 112 samples of spices (24 caraway, 20 coriander, 25 curcuma, 20 black pepper and 23 red pepper) and 110 samples of dried nuts (44 almonds, 42 peanuts and 24 pistachio) purchased from popular markets in 24 regions of Tunisia were analyzed for ochratoxin A (OTA) by fluorescence HPLC. The average levels of contamination of OTA found in spice samples were 244, 206, 290, 274 and 203 µg/kg, respectively, for caraway, coriander, curcuma, black pepper and red pepper. Concerning dried nut samples, the average levels were 61, 60 and 89 µg/kg, respectively, for almonds, peanuts and pistachio. Contamination levels were higher than the usual norms (10.0 OTA µg/kg) established by the European Commission in 2005 . This survey is the first to be carried out on the natural occurrence of OTA in the main spices and dried nuts consumed by the Tunisian population.