Niclosamide (NICLO) is a recognized antiparasitic drug being repositioned for Helicobacter pylori. The present work aimed to formulate NICLO nanocrystals (NICLO-NCRs) to produce a higher dissolution rate of the active ingredient and to incorporate these nanosystems into a floating solid dosage form to release them into the stomach slowly. For this purpose, NICLO-NCRs were produced by wet-milling and included in a floating Gelucire l3D printed tablet by semi-solid extrusion, applying the Melting solidification printing process (MESO-PP) methodology. The results obtained in TGA, DSC, XRD and FT-IR analysis showed no physicochemical interactions or modifications in the crystallinity of NICLO-NCR after inclusion in Gelucire 50/13 ink. This method allowed the incorporation of NICLO-NCRs in a concentration of up to 25% w/w. It achieved a controlled release of NCRs in a simulated gastric medium. Moreover, the presence of NICLO-NCRs after redispersion of the printlets was observed by STEM. Additionally, no effects on the cell viability of the NCRs were demonstrated in the GES-1 cell line. Finally, gastroretention was demonstrated for 180 min in dogs. These findings show the potential of the MESO-PP technique in obtaining slow-release gastro-retentive oral solid dosage forms loaded with nanocrystals of a poorly soluble drug, an ideal system for treating gastric pathologies such as H. pylori.

Localized disorders, even though originally confined to a specific body part, can progress into potentially life-threatening systemic disorders if treated inappropriately. Local treatment is often highly challenging due to poor penetration of therapeutic agents from their vehicles into the affected body site. Systemic treatment on the other hand often comes with unspecific side effects. The skin is the largest organ of the body, and conditions such as wounds and bacterial or fungal infections disrupt its natural barrier properties, important for the homeostasis of the human body. Advanced drug delivery systems for treating these conditions could greatly improve the treatment outcome and patient compliance. Other parts of the body that are of interest regarding localized treatment are, for example, the eyes along with mucosal tissues which are present in the vagina and lungs. Rather than focusing on specific diseases or parts of the body, this review provides an overview of the different drug delivery platforms that have been employed for enhanced local treatment. The following systems will be discussed: nanoparticle-based systems, such as nanocrystals, polymeric, lipidic, and inorganic nanoparticles, and nanogels; cyclodextrin inclusion complexes; and several devices like microarray patches, wound dressings, and films.

Domperidone (DOM) is a drug commonly used to treat nausea and vomiting, as well as gastrointestinal disorders. However, its low solubility and extensive metabolism pose significant administration challenges. In this study, we aimed to improve DOM solubility and avoid its metabolism by developing nanocrystals (NC) of DOM through a 3D printing technology—melting solidification printing process (MESO-PP)—to be delivered via a solid dosage form (SDF) that can be administered sublingually. We obtained DOM-NCs using the wet milling process and designed an ultra-rapid release ink (composed of PEG 1500, propylene glycol, sodium starch glycolate, croscarmellose sodium, and sodium citrate) for the 3D printing process. The results demonstrated an increase in the saturation solubility of DOM in both water and simulated saliva without any physicochemical changes in the ink as observed by DSC, TGA, DRX, and FT-IR. The combination of nanotechnology and 3D printing technology enabled us to produce a rapidly disintegrating SDF with an improved drug-release profile. This study demonstrates the potential of developing sublingual dosage forms for drugs with low aqueous solubility using nanotechnology and 3D printing technology, providing a feasible solution to the challenges associated with the administration of drugs with low solubility and extensive metabolism in pharmacology.

Nanocrystals (NCs) combined with microneedles (MNs) represent an emerging drug delivery platform with significant potential to overcome challenges in the administration of poorly-water soluble drugs. This next generation delivery approach increases the surface area and dissolution rate of drugs via the production of NCs, overcoming the skin barrier in a minimally invasive manner, afforded by the MN technology. This focused review summarizes the research from the past eight years on the development of NC-loaded MN systems. It discusses the formulation strategies, characterization, and therapeutic benefits reported in the literature, highlighting controlled dissolution and sustained release capabilities. The review also addresses critical challenges related to clinical translation, such as validation of therapeutic efficacy and broadening clinical applications. NC - MN systems have shown promise in self-administered and long-acting therapies. Yet, stability issues, manufacturing reproducibility, and regulatory uncertainty still remain barriers to translation. Progress in scalable manufacturing and regulatory engagement is encouraging, but robust in vivo data and standardized characterization are needed. Continued interdisciplinary work and collaboration across academia, industry, and regulatory agencies will be vital to realize the clinical potential of this platform.

Aim: Benznidazole (BNZ), a class-II drug, is the primary treatment for Chagas disease, but its low aqueous solubility presents challenges in formulation and efficacy. Nanosuspensions (NS) could potentially address these issues. Methods: BNZ-NS were prepared using a simple, organic solvents-free nano-milling approach. Physicochemical characterizations were conducted on both NS and lyophilized solid-state BNZ-nanocrystals (NC). Results: BNZ-NS exhibited particle size <500 nm, an acceptable polydispersity index (0.23), high Z-potential, and physical stability for at least 90 days. BNZ-NC showed tenfold higher solubility than pure BNZ. Dissolution assays revealed rapid BNZ-NS dissolution. BNZ-NC demonstrated biocompatibility on an eukaryotic cell and enhanced BNZ efficacy against trypomastigotes of Trypanosoma cruzi. Conclusion: BNZ-NS offers a promising alternative, overcoming limitations associated with BNZ for optimized pharmacotherapy.