Particle Design of Drugs via Spherical Crystallization: A Review from Fundamental Aspects to Technology Development

In the pharmaceutical industry, the production process of most active pharmaceutical ingredients involves at least one crystallization step. Design of drug spheres via various spherical crystallization technologies can impart crystals with certain superior attributes including high flowability and compressibility as well as excellent mechanical properties. Some new spherical crystallization approaches and design principles have been proposed in recent years. This review aims to review the up-to-date design principles and preparation technologies of drug spheres, providing a guide for design, preparation, and performance evaluation of the drug spheres. Herein, we review the mechanisms and design principles of the spherical crystallization first, and subsequently various technologies reported in the literature are reviewed with the critical process parameters being analyzed. Lastly, the challenges facing the development of spherical crystallization for drugs are discussed

Direct Molten Polymerization Synthesis of Highly Active Samarium Manganese Perovskites with Different Morphologies for VOC Removal

A morphology-controlled molten polymerization route was developed to synthesize SmMnO3 (SMO) perovskite catalysts with netlike (SMO-N), granular-like (SMO-G), and bulk (SMO-B) structures. The SMO perovskites were formed directly by a molten polymerization method, and their morphologies were controlled by using the derivative polymers as templates. Among all catalysts, the porous SMO-N exhibited the highest activity, over which the toluene, benzene, and o-xylene were completely oxidized to CO2 at 240, 270, and 300 °C, respectively, which was comparable to that of typical noble-metal catalysts. The apparent activation energies of toluene over SMO-N (56.4 kJ·mol–1) was much lower than that of SMO-G (70.8 kJ·mol–1) and SMO-B (90.1 kJ·mol–1). Based on the results of scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and H2 temperature-programmed reduction characterization, we deduce that the excellent removal efficiency of volatile organic compounds (VOCs) over SMO-N catalyst was attributable to the special structure, high surface Mn4+/Mn3+ and Olatt/Oads molar ratios, and strong reducibility. Due to the high activity, low cost, and simple preparation strategy, the SMO catalyst is a promising catalyst for VOC removal

Silver(I) Promoted the C4–H Bond Phosphonation of 1‑Naphthylamine Derivatives with H‑Phosphonates

A simple and efficient protocol for silver-promoted direct C–H phosphonation of 1-naphthylamine derivatives with H-phosphonates was described. This reaction proceeded smoothly for 1-naphthylamine derivatives at the C4 site, providing a facile and efficient route to 4-phosphonated 1-naphthylamine derivatives. This phosphonation could tolerate a diverse type of functional groups at the pyridinyl and naphthyl moieties. Further functionalization of the phosphonated product was also explored at the C2 and C8 sites, such as fluoridation, methylation, methoxylation, and amination. In addition, DFT studies of the reaction intermediate showed that the most electrophilic reactive site is at the C4 site in the naphthyl ring

Highly Efficient Hydrogel Encapsulation of Hydrophobic Drugs via an Organic Solvent-Free Process Based on Oiling-Out Crystallization and a Mechanism Study

Hydrogel encapsulation of hydrophobic drugs is challenging because the hydrophilic nature of hydrogel is highly likely to result in a low loading efficiency (LE), and complex encapsulation procedures are usually inevitable in the previously reported encapsulation approaches. The objective of this study is to develop a highly efficient and ecofriendly technique for embedding hydrophobic drugs in hydrogels and provide a good guide to instruct the process design. Through the combination of oiling-out crystallization and ionotropic gelation, drug-loaded hydrogel beads were prepared via an organic solvent-free method, achieving an impressive LE of 83.3%. Apart from encapsulation of a single drug, this technique also allows the incorporation of dual drugs in the hydrogel matrix via a simple heating–cooling operation. The hydrogel encapsulation of multicomponent drug microparticles is expected to realize combination therapy, thus offering another promising way to reduce the drug dosage and minimize potential side effects. Furthermore, the oiling-out behavior was investigated using dissipative particle dynamics and density functional theory, enabling the establishment of a theoretical foundation for the design of encapsulation processes. Although ibuprofen and indomethacin were used as representative drugs in this research, this innovative technology can be effectively extended to a wide range of hydrophobic drugs

Site-Selective in Situ Growth-Induced Self-Assembly of Protein–Polymer Conjugates into pH-Responsive Micelles for Tumor Microenvironment Triggered Fluorescence Imaging

Self-assembly of site-selective protein–polymer conjugates into stimuli-responsive micelles is interesting owing to their potential biomedical applications, ranging from molecular imaging to drug delivery, but remains a significant challenge. Herein we report a method of site-selective in situ growth-induced self-assembly (SIGS) to synthesize site-specific human serum albumin-poly­(2-(diisopropylamino)­ethyl methacrylate) (HSA-PDPA) conjugates that can in situ self-assemble into pH-responsive micelles with tunable morphologies. Indocyanine green (ICG) was selectively loaded into the core of sphere-like HSA-PDPA micelles to form pH-responsive fluorescence nanoprobes. The nanoprobes rapidly dissociated into protonated individual unimers at a transition pH of around 6.5, that is the extracellular pH of tumors, which resulted in a sharp fluorescence increase and markedly enhanced cellular uptake. In a tumor-bearing mouse model, they exhibited greatly enhanced tumor fluorescence imaging as compared to ICG alone and pH-nonresponsive nanoprobes. These findings suggest that pH-responsive and site-selective protein–polymer conjugate micelles synthesized by SIGS are promising as a new class of tumor microenvironment-responsive nanocarriers for enhanced tumor imaging and therapy

Combination of Merocel sponge with Lipopolysaccharide to establish rat rhinosinusitis model

Abstract Objective The study aimed to investigate the feasibility of establishing rhinosinusitis model in rats combinated with Lipopolysaccharide (LPS) and merocel sponge. Methods SD (Sprague Dawley) rats that underwent nasal obstruction using Merocel sponge packing, rats with LPS instillation alone, and rats with both nasal obstruction and LPS instillation were used to establish rat models of rhinosinusitis. After the models were established, the nasal symptoms of rats were recorded, the histopathological examination and Transmission Electron Microscopy (TME) of the sinus tissue were performed and the levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6) in the blood were also analyzed. The expressions of Aquaporin-5 (AQP5), Occludin, Toll-Like Receptor-4 (TLR4), Medullary differentiation factor 88 (MyD88) and phosphorylated (p)-p65 protein were detected by Western blot to evaluate the effect and mechanism of the experimental models. Results We found that compared with the control group and LPS group, the sinusitis symptom scores in the Merocel sponge combined with LPS group were significantly increased; the respiratory epithelia of the maxillary sinus were degenerated, cilia were detached, and even inflammatory cell infiltration occurred; the levels of TNF-α and IL-6 were increased; the expression of AQP5 and Occludin protein was decreased; and the expressions of TLR4, MyD88, and p-p65 protein were increased. Conclusion For the first time, we successfully established a rat rhinosinusitis model using Merocel sponge with LPS and explored the possible mechanism of LPS action.</div

Magnetically Actuated Peanut Colloid Motors for Cell Manipulation and Patterning

We report a magnetically actuated peanut-shaped hematite colloid motor that can not only move in a rolling or wobbling mode in fluids but also perform single cell manipulation and patterning in a noncontact way. The peanut motor in a rolling mode can reach a maximal velocity of 10.6 μm s^–1 under a rotating magnetic field of 130 Hz and 6.3 mT and achieve a more precisely controllable motion in predefined tracks. While in a wobbling mode, the motor reaches a maximal velocity of 14.5 μm s^–1 under a conical rotating magnetic field of 80 Hz and 6.3 mT and can climb over steep slopes to adapt the motor for more complex environments. The fluid flow simulation results reveal that the difference between two movement modes mostly comes from the distribution discrepancy of the flow fields near the motors. Through the integration of the rolling and wobbling movement, these peanut motors can autonomously transport and release cells to a predefined site and thus form complex cell patterns without a physical contact. Such magnetically actuated peanut colloid motors afford a biofriendly technique for manipulation and patterning of cells, cell measurements, and intracellular communication investigations