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A pioneering approach in the domain of transdermal drug delivery systems (TDDS) is introduced by using microneedles (MNs) fabricated from an amorphous solid dispersion comprising only a model drug and an amphiphilic block copolymer to form a drug nanoformulation upon MN dissolution. To maximize drug loading and ensure consistent release, a minimalist formulation that achieves 40 wt% drug loading, which is a significant improvement over existing methods, is developed. Using scanning electron microscopy, the morphology of MNs is examined across a spectrum of drug loading ratios, demonstrating the consistency in structure and integrity. Mechanical testing confirms the MNs' proficiency in effective skin penetration. A comparative study on the formation of polymeric micelles underscores the innovative concept of a “nano‐in‐micro drug delivery system”. The results demonstrate that MNs manufactured from an amorphous solid dispersion of drug and amphiphilic block copolymer with ultra‐high loading enhance the availability and release dynamics of hydrophobic drugs, positioning them as a tool for enhancing TDDS. This study sets a new benchmark in the utilization of polymer‐drug nanoformulations for transdermal applications and underscores the capacity for high drug loading and the creation of adaptable drug delivery mechanisms for the studied amphiphilic block copolymer. [ABSTRACT FROM AUTHOR]

The current situation, heavily influenced by the ongoing pandemic, puts vaccines back into the spotlight. However, the conventional and traditional vaccines present disadvantages, particularly related to immunogenicity, stability, and storage of the final product. Often, such products require the maintenance of a "cold chain," impacting the costs, the availability, and the distribution of vaccines. Here, after a recall of the mode of action of vaccines and the types of vaccines currently available, we analyze the past, present, and future of vaccine formulation. The past focuses on conventional formulations, the present discusses the use of nanoparticles for vaccine delivery and as adjuvants, while the future presents microneedle patches as alternative formulation and administration route. Finally, we compare the advantages and disadvantages of injectable solutions, nanovaccines, and microneedles in terms of efficacy, stability, and patient-friendly design. Different approaches to vaccine formulation development, the conventional vaccine formulations from the past, the current development of lipid nanoparticles as vaccines, and the near future microneedles formulations are discussed in this review. [ABSTRACT FROM AUTHOR]

Work on thermal pools at Poggetti Vecchi in Grosseto, Italy, exposed an up to 3-meter-thick succession of seven sedimentary units. Unit 2 in the lower portion of the succession contained vertebrate bones, mostly of the straight-tusked elephant, Palaeoloxodon antiquus, commingled with stone, bone, and wooden tools. Thermal carbonates overlying Unit 2 are radiometrically dated to the latter part of the middle Pleistocene. This time span indicates that early Neanderthals produced the human artifacts from Poggetti Vecchi. The elephant bones belong to seven individuals of different ages. Sedimentary facies analysis and paleoecological evidence suggest a narrow lacustrine-palustrine embayment affected by water-level fluctuations and, at times, by hydrothermal water. Cyclic lake-level variations were predominantly forced by the rapid climatic fluctuations that occurred at Marine Isotope Stage (MIS) 6–7 transition and throughout the MIS 6. Possibly an abrupt, intense, and protracted cold episode during the onset of MIS 6 led to the sudden death of the elephants, which formed an unexpected food resource for the humans of the area. The Poggetti Vecchi site adds new information on the behavioral plasticity and food procurement strategies that early Neanderthals were able to develop in Italy during the middle to the late Pleistocene transition. [ABSTRACT FROM PUBLISHER]

Geomorphologic, stratigraphic, faunistic, palynological and 14C analyses were carried out in the area of the mouth of the Garigliano River characterized by two strand plains that are referred to the Eutyrrhenian and the Holocene, rimming two depressed zones separated by the Garigliano River channel. This study depicts the palaeoenvironmental evolution over the last 8200 years and the landscape context at the time of Minturnae Roman colony. Between 8200 and 7500 yr BP, a wet zone occurred in the northern zone, whereas in the southern part, a lagoon developed. During the final transgression stage and the beginning of the sea level still stand (7500–5500 yr BP), a freshwater marsh formed in the northern zone, and the width of the southern lagoon decreased. Between 5500 and 3000 yr BP, the coastal barrier changed into a delta cusp, a freshwater marsh also appeared in the southern part and the river wandered between the twin marshes. Because of local uplift, previously unknown in this area, part of the floor of the southern marsh emerged, and after 4000 yr BP, both marshes became coastal ponds with prevailing clastic sedimentation. A progressive increment in anthropic forcing on the land took place after 3000 yr BP. The Marica sanctuary was built (7th century BC), and the Roman colony of Minturnae was developed beginning the 3rd century BC. The shallow depth of the ponds prevented their use as harbours, and saltwork plants can be ruled out based on the faunal and palynological data. The ongoing infilling of both ponds was never completed, and their reclamation is still in progress. [ABSTRACT FROM AUTHOR]