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Oral mucositis in the oral cavity, caused by radiation therapy and chemotherapy, requires personalized care and therapy due to variations in the lesions of patients. In the present study, we fabricated a model of personalized oral film containing an ibuprofen/lidocaine ionic liquid (IL) for patients with oral mucositis using a pressure-assisted microsyringe-type 3D printer at room temperature. The film contained a Eudragit polymer (L100, EPO, or RSPO) to make the film solid, and the printer ink was composed of organo ink (organic solvent to dissolve both drugs and the Eudragit polymer). The viscosity of the printer ink was assessed to investigate its extrudability. The contact angle and the surface tension at the interface between each liquid printer ink and a solid polypropylene sheet were measured to determine the retention of the ink in 3D printing. The physical properties of IL-loaded Eudragit-based dry films were examined by X-ray diffraction and differential scanning calorimetry. Dissolution tests indicated that IL-loaded films containing a Eudragit polymer exhibited different drug release rates in phosphate buffer (pH 6.8; Eudragit L100 > IL alone > Eudragit EPO > Eudragit RSPO). These results provide useful information for the specific fabrication of IL-loaded polymer-based films using organo inks and pressure-assisted microsyringe-type 3D printers.

Oral leukoplakia, which presents as white lesions in the oral cavity, including on the tongue, is precancerous in nature. Conservative treatment is preferable, since surgical removal can markedly reduce the patient’s quality of life. In the present study, we focused on the flavonoid apigenin as a potential compound for preventing carcinogenesis, and an apigenin-loaded mucoadhesive oral film was prepared using a three-dimensional (3D) bioprinter (semi-solid extrusion-type 3D printer). Apigenin-loaded printer inks are composed of pharmaceutical excipients (HPMC, CARBOPOL, and Poloxamer), water, and ethanol to dissolve apigenin, and the appropriate viscosity of printer ink after adjusting the ratios allowed for the successful 3D printing of the film. After drying the 3D-printed object, the resulting film was characterized. The chemopreventive effect of the apigenin-loaded film was evaluated using an experimental rat model that had been exposed to 4-nitroquinoline 1-oxide (4NQO) to induce oral carcinogenesis. Treatment with the apigenin-loaded film showed a remarkable chemopreventive effect based on an analysis of the specimen by immunohistostaining. These results suggest that the apigenin-loaded mucoadhesive film may help prevent carcinogenesis. This successful preparation of apigenin-loaded films by a 3D printer provides useful information for automatically fabricating other tailored films (with individual doses and shapes) for patients with oral leukoplakia in a future clinical setting.

3D printing technology has been applied to various fields and its medical applications are expanding. Here, we fabricated implantable 3D bio-printed hydrogel patches containing a nanomedicine as a future tailored cancer treatment. The patches were prepared using a semi-solid extrusion-type 3D bioprinter, a hydrogel-based printer ink, and UV-LED exposure. We focused on the composition of the printer ink and semi-synthesized fish gelatin methacryloyl (F-GelMA), derived from cold fish gelatin, as the main component. The low viscosity of F-GelMA due to its low melting point was remarkably improved by the addition of carboxymethyl cellulose sodium (CMC), a pharmaceutical excipient. PEGylated liposomal doxorubicin (DOX), as a model nanomedicine, was incorporated into the hydrogel and liposome stability after photo-polymerization was evaluated. The addition of CMC inhibited particle size increase. Three types of 3D-designed patches (cylinder, torus, gridlines) were produced using a 3D bioprinter. Drug release was dependent on the shape of the 3D-printed patches and UV-LED exposure time. The current study provides useful information for the preparation of 3D printed nanomedicine-based objects.

The cocrystal formation of pharmaceuticals can improve the various physical properties of drugs, such as solubility, without the need for chemical modification of the drug substances. In the present study, we prepared cocrystals of cilostazol and additive coformers (derivatives of hydroxybenzoic acid) using a spray drying method. Based on the preparation of the cocrystals of cilostazol and the coformers as reported previously, the characteristics of the cilostazol cocrystals prepared using solvent evaporation, slurry, and spray drying methods were compared. The physical characterization revealed that the spray drying method successfully produced cilostazol–4-hydroxybenzoic acid and cilostazol–2,4-dihydroxybenzoic acid cocrystals, whereas samples of cocrystals of cilostazol and 2,5-dihydroxybenzoic acid produced via the spray drying process appeared to contain coformer polymorphs. The dissolution of cilostazol was improved using the spray-dried cocrystal samples composed of coformers compared to samples prepared using cilostazol alone or a physical mixture. The present results provide useful information regarding the manufacture of cilostazol cocrystals and pharmaceutical cocrystals via spray drying in large-batch production.

Inhaled formulations are promising for pulmonary and systemic non-pulmonary diseases. Functional engineered particles including drugs and drug-loaded nanocarriers have been anticipated because they can improve drug delivery efficacy against target sites in the lungs or blood. In this review, unique spray nozzles (e.g., four-fluid spray nozzle and two-solution mixing type nozzle) for the preparation of nanocomposite particles which mean microparticles containing drug nanoparticles are described. These nozzles can produce nanocomposite particles in one-step and their spray drying system is suitable for scaling-up. Nanocomposite particles are useful in improving drug absorption and delivery efficacy against alveolar macrophages. In addition, recent studies on several pulmonary diseases (tuberculosis, lung cancer, cystic fibrosis, pneumonia, vaccine and others) and related inhaled formulations were also reviewed.

Dissolution of water-insoluble curcumin at a high concentration (>100 μM) is achieved by femtosecond-laser ablation in an aqueous solution containing cyclodextrin compounds at room temperature. The curcumin solution is freeze-dried to yield an orange powder, which is also highly soluble in water (ca. 1 mM). The dissolved curcumin compound has cytotoxic activity toward lung cancer cells. [ABSTRACT FROM AUTHOR]