Fast-dissolving oral films (FDFs) provide an alternative approach to increase consumer acceptance by advantage of rapid dissolution and administration without water. Usually, FDFs require taste-masking agents. However, inclusion of these excipients could make developing the formulation a challenging task. Hence, this work employed fused-deposition modeling three-dimensional printing to produce single-layered FDFs (SLFDFs), or multilayered FDFs (MLFDFs) films, with taste-masking layers being separated from drug layer. Filaments were prepared containing polyethylene oxide (PEO) with ibuprofen or paracetamol as model drugs at 60°C. Also, filaments were produced containing polyvinyl alcohol and paracetamol at 130°C. Furthermore, a filament was prepared containing PEO and strawberry powder for taste-masking layer. FDFs were printed at temperatures of 165°C (PEO) or 190°C (polyvinyl alcohol) with plain or mesh designs. High-performance liquid chromatography and mass spectroscopy analysis indicated active ingredient stability during film preparation process. SLFDFs had thicknesses as small as 197 ± 21 μm, and MLFDFs had thicknesses starting from 298 ± 15 μm. Depending on the formulation and design, mesh SLFDFs presented disintegration time as short as 42 ± 7 s, and this was 48 ± 5 s for mesh MLFDFs. SLFDFs showed drug content uniformity in the range of 106.0%-112.4%. In conclusion, this study provides proof-of-concept for the manufacturing of FDFs by using 3D printing.

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The prevalence of neurological/neurodegenerative diseases, such as Alzheimer's disease is known to be increasing due to an aging population and is anticipated to further grow in the decades ahead. The treatment of brain diseases is challenging partly due to the inaccessibility of therapeutic agents to the brain. An increasingly important observation is that the physiology of the brain alters during many brain diseases, and aging adds even more to the complexity of the disease. There is a notion that the permeability of the blood–brain barrier (BBB) increases with aging or disease, however, the body has a defense mechanism that still retains the separation of the brain from harmful chemicals in the blood. This makes drug delivery to the diseased brain, even more challenging and complex task. Here, the physiological changes to the diseased brain and aged brain are covered in the context of drug delivery to the brain using nanoparticles. Also, recent and novel approaches are discussed for the delivery of therapeutic agents to the diseased brain using nanoparticle based or magnetic resonance imaging guided systems. Furthermore, the complement activation, toxicity, and immunogenicity of brain targeting nanoparticles as well as novel in vitro BBB models are discussed.

With estimated worldwide cost over $1 trillion just for dementia, diseases of the central nervous system pose a major problem to health and healthcare systems, with significant socio-economic implications for sufferers and society at large. In the last two decades, numerous strategies and technologies have been developed and adapted to achieve drug penetration into the brain, evolving alongside our understanding of the physiological barriers between the brain and surrounding tissues. The blood brain barrier (BBB) has been known as the major barrier for drug delivery to the brain. Both invasive and minimally-invasive approaches have been investigated extensively, with the minimallyinvasive approaches to drug delivery being more suitable. Peptide based brain targeting has been explored extensively in the last two decades. In this review paper, we focused on self-assembled peptides, shuttle peptides and nanoparticles drug delivery systems decorated/conjugated with peptides for brain penetration.Abbreviations

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