Transdermal drug delivery represents an appealing alternative to conventional drug administration systems. In fact, due to their high patient compliance, the development of dissolvable and biodegradable polymer microneedles has recently attracted great attention. Although stamp-based procedures guarantee high tip resolution and reproducibility, they have long processing times, low levels of system engineering, are a source of possible contaminants, and thermo-sensitive drugs cannot be used in conjunction with them. In this work, a novel stamp-based microneedle fabrication method is proposed. It provides a rapid room-temperature production of multi-compartmental biodegradable polymeric microneedles for controlled intradermal drug release. Solvent casting was carried out for only a few minutes and produced a short dissolvable tip made of polyvinylpyrrolidone (PVP). The rest of the stamp was then filled with degradable poly(lactide-co-glycolide) (PLGA) microparticles (μPs) quickly compacted with a vapor-assisted plasticization. The outcome was an array of microneedles with tunable release. The ability of the resulting microneedles to indent was assessed using pig cadaver skin. Controlled intradermal delivery was demonstrated by loading both the tip and the body of the microneedles with model therapeutics; POXA1b laccase from Pleurotus ostreatus is a commercial enzyme used for the whitening of skin spots. The action and indentation of the enzyme-loaded microneedle action were assessed in an in vitro skin model and this highlighted their ability to control the kinetic release of the encapsulated compound.
Mainly designed and realized as a painless alternative to the hypodermic syringe, microneedle-based devices are currently approaching commercial market placement. The considerable academic and industrial investment in this technology is reflected by a multitude of papers published and patents registered every year, which is also a sign of a field in full fermentation. New materials and innovative methodologies are continuously exploited in search of the best performance at the lowest cost. For these reasons, an updated review, focused predominantly on the last year of scientific production, is a useful guideline in this rapidly changing panorama. This report provides a critical review of microneedle technologies presented in the very recent literature with a particular focus on those closest to the needs of the healthcare field. Although a few devices are already commercial, further effort is still needed to achieve complete clinical translation and therapeutic efficacy competitive with or superior to those of the devices used as standards and adopted by national health systems.
Microneedles (MNs) are an emerging technology in pharmaceutics and biomedicine, and are ready to be commercialized in the world market. However, solid microneedles only allow small doses and time-limited administration rates. Moreover, some well-known and already approved drugs need to be re-formulated when supplied by MNs. Instead, hollow microneedles (HMNs) allow for rapid, painless self-administrable microinjection of drugs in their standard formulation. Furthermore, body fluids can be easily extracted for analysis by a reverse use of HMNs, thus making them perfect for sensing issues and theranostics applications. The fabrication of HMNs usually requires several many-step processes, increasing the costs and consequently decreasing the commercial interest. Photolithography is a well-known fabrication technique in microelectronics and microfluidics that fabricates MNs. In this paper, authors show a proof of concept of a patented, easy and one-shot fabrication of two kinds of HMNs: (1) Symmetric HMNs with a “volcano” shape, made by using a photolithographic mask with an array of transparent symmetric rings; and (2) asymmetric HMNs with an oblique aperture, like standard hypodermic steel needles, made by using an array of transparent asymmetric rings, defined by two circles, which centers are slightly mismatched. Simulation of light propagation, fabrication process, and preliminary results on ink microinjection are presented.
Interstitial fluid (ISF) extraction and analysis are challenges that can be tackled by Hollow MicroNeedles (HMNs) technology, overcoming most of the difficulties associated with in situ detection. Herein, a plasmonic transducer, composed of gold nanoparticles embedded in poly(ethylene glycol) diacrylate (PEGDA) hydrogels, is integrated in the inner cavity of HMNs to detect biomarkers from the ISF‐based point‐of‐care. The wearable HMN‐based patch is used for minimally invasive pierce of the skin. The large swelling capability of the plasmonic transducer allows the uptake of ISF by capillarity. Biotin, as a small model molecule, is efficiently collected in the inner cavity of HMN and its high specificity with the streptavidin is exploited as a validation of the plasmonic nanocomposite functionality embedded within. The recognition of biotin is achieved in dual‐optical mode: the localized surface plasmon resonance (label‐free) and the metal‐enhanced fluorescence (label‐based). Overall, the proposed HMN‐based patch for target sensing in ISF can represent a novel point‐of‐use device for the detection of biomarkers as an alternative to conventional hospital or lab settings to help faster medical decision‐making.
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