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Recently, various innovative technologies have been developed for the enhanced delivery of biologics as attractive formulation targets including polymeric micro and nanoparticles. Combined with personalized medicine, this area can offer a great opportunity for the improvement of therapeutics efficiency and the treatment outcome. Herein, a novel manufacturing method has been introduced to produce protein-loaded chitosan particles with controlled size. This method is based on an additive manufacturing technology that allows for the designing and production of personalized particulate based therapeutic formulations with a precise control over the shape, size, and potentially the geometry. Sprayed multi adsorbed-droplet reposing technology (SMART) consists of the high-pressure extrusion of an ink with a well determined composition using a pneumatic 3D bioprinting approach and flash freezing the extrudate at the printing bed, optionally followed by freeze drying. In the present study, we attempted to manufacture trypsin-loaded chitosan particles using SMART. The ink and products were thoroughly characterized by dynamic light scattering, rheometer, Scanning Electron Microscopy (SEM), and Fourier Transform Infra-Red (FTIR) and Circular Dichroism (CD) spectroscopy. These characterizations confirmed the shape morphology as well as the protein integrity over the process. Further, the effect of various factors on the production were investigated. Our results showed that the concentration of the carrier, chitosan, and the lyoprotectant concentration as well as the extrusion pressure have a significant effect on the particle size. According to CD spectra, SMART ensured Trypsin's secondary structure remained intact regardless of the ink composition and pressure. However, our study revealed that the presence of 5% (w/v) lyoprotectant is essential to maintain the trypsin's proteolytic activity. This study demonstrates, for the first time, the viability of SMART as a single-step efficient process to produce biologics-based stable formulations with a precise control over the particulate morphology which can further be expanded across numerous therapeutic modalities including vaccines and cell/gene therapies. [ABSTRACT FROM AUTHOR]

[Display omitted] Production of amorphous solid dispersions (ASDs) is an effective strategy to promote the solubility and bioavailability of poorly water soluble medicinal substances. In general, ASD is manufactured using a variety of classic and modern techniques, most of which rely on either melting or solvent evaporation. This proof-of-concept study is the first ever to introduce electromagnetic drop-on-demand (DoD) technique as an alternative solvent evaporation-based method for producing ASDs. Herein 3D printing of ASDs for three drug-polymer combinations (efavirenz-Eudragit L100-55, lumefantrine-hydroxypropyl methylcellulose acetate succinate, and favipiravir-polyacrylic acid) was investigated to ascertain the reliability of this technique. Polarized light microscopy, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and Fourier Transform Infrared (FTIR) spectroscopy results supported the formation of ASDs for the three drugs by means of DoD 3D printing, which significantly increases the equilibrium solubility of efavirenz from 0.03 ± 0.04 µg/ml to 21.18 ± 4.20 µg/ml, and the equilibrium solubility of lumefantrine from 1.26 ± 1.60 µg/ml to 20.21 ± 6.91 µg/ml. Overall, the reported findings show how this new electromagnetic DoD technology can have a potential to become a cutting-edge 3D printing solvent-evaporation technique for on-demand and continuous manufacturing of ASDs for a variety of drugs. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing is a promising approach for the stabilization and delivery of non-living biologics. This versatile tool builds complex structures and customized resolutions, and has significant potential in various industries, especially pharmaceutics and biopharmaceutics. Biologics have become increasingly prevalent in the field of medicine due to their diverse applications and benefits. Stability is the main attribute that must be achieved during the development of biologic formulations. 3D printing could help to stabilize biologics by entrapment, support binding, or crosslinking. Furthermore, gene fragments could be transited into cells during co-printing, when the pores on the membrane are enlarged. This review provides: (i) an introduction to 3D printing technologies and biologics, covering genetic elements, therapeutic proteins, antibodies, and bacteriophages; (ii) an overview of the applications of 3D printing of biologics, including regenerative medicine, gene therapy, and personalized treatments; (iii) information on how 3D printing could help to stabilize and deliver biologics; and (iv) discussion on regulations, challenges, and future directions, including microneedle vaccines, novel 3D printing technologies and artificial-intelligence-facilitated research and product development. Overall, the 3D printing of biologics holds great promise for enhancing human health by providing extended longevity and enhanced quality of life, making it an exciting area in the rapidly evolving field of biomedicine. [ABSTRACT FROM AUTHOR]

Conventional oral dosage forms may not always be optimal especially for those patients suffering from dysphasia or difficulty swallowing. Development of suitable oral thin films (OTFs), therefore, can be an excellent alternative to conventional dosage forms for these patient groups. Hence, the main objective of the current investigation is to develop oral thin film (OTF) formulations using novel solvent-free approaches, including additive manufacturing (AM), hot-melt extrusion, and melt casting. AM, popularly recognized as 3D printing, has been widely utilized for on-demand and personalized formulation development in the pharmaceutical industry. Additionally, in general active pharmaceutical ingredients (APIs) are dissolved or dispersed in polymeric matrices to form amorphous solid dispersions (ASDs). In this study, acetaminophen (APAP) was selected as the model drug, and Klucel™ hydroxypropyl cellulose (HPC) E5 and Soluplus® were used as carrier matrices to form the OTFs. Amorphous OTFs were successfully manufactured by hot-melt extrusion and 3D printing technologies followed by comprehensive studies on the physico-chemical properties of the drug and developed OTFs. Advanced physico-chemical characterizations revealed the presence of amorphous drug in both HME and 3D printed films whereas some crystalline traces were visible in solvent and melt cast films. Moreover, advanced surface analysis conducted by Raman mapping confirmed a more homogenous distribution of amorphous drugs in 3D printed films compared to those prepared by other methods. A series of mathematical models were also used to describe drug release mechanisms from the developed OTFs. Moreover, the in vitro dissolution studies of the 3D printed films demonstrated an improved drug release performance compared to the melt cast or extruded films. This study suggested that HME combined with 3D printing can potentially improve the physical properties of formulations and produce OTFs with preferred qualities such as faster dissolution rate of drugs. [ABSTRACT FROM AUTHOR]

• Additive manufacturing is quickly gaining momentum in the fight against cancer. • Major applications in cancer diagnostics, delivery vehicles and in vitro cancer models are discussed. • Stimuli-responsive shape-shifting robots ensure localized cancer-site-mediated delivery. • Regulatory and cost-related challenges limit widespread adoption. 3D printing has emerged as a powerful tool demonstrating effectiveness in early screening and targeted delivery for various types of tumors. Although the applications of additive manufacturing for cancer are widespread, the issues of scaling up, quality control and specificity remain. This review presents a comprehensive analysis of the current landscape of use of additive manufacturing in cancer diagnostics and treatment. Furthermore, it proceeds to elucidate the prominent current and future applications of 4D- and 5D-printed micro-swimmers in cancer treatment with particular emphasis on the significant progress made in magnetic, biological and light-based propulsion microrobots. Lastly, the current limitations and future research directions are enumerated. In summary, this paper serves as a comprehensive exploration of the remarkable contributions of additive manufacturing to the diagnosis and treatment of cancer. [ABSTRACT FROM AUTHOR]