Shiyuan Liu

Solvent penetration mediated phase transformation for the preparation of aggregated particles with well-defined shape

We report here a unique method for the preparation of aggregated crystals with well-defined shape and size using a solvent penetration-mediated phase transformation. An unusually fast phase transformation of sulfadiazine was observed. The aggregated sulfadiazine crystals are obtained through a water penetration mediated transformation of sulfadiazine N-methyl pyrrolidone solvate. The aggregated particles keep the same shape and size of the parent crystals.

A novel high drug loading mussel-inspired polydopamine hybrid nanoparticle as a pH-sensitive vehicle for drug delivery

A novel high drug loading pH-cleavable polymer hybrid nanoparticle was prepared via doxorubicin (DOX) grafted onto PEGylated, mussel-inspired polydopamine (PDA) and then coated onto hollow silica nanoparticles for drug delivery. A series of characterization shed light on the formation mechanisms of PDA coatings on hollow silica. We hypothesized that dopamine was first absorbed onto the surface of hollow silica and then began self-polymerization. A Dox-containing thiol moiety was fabricated with conjugation between doxorubicin hydrochloride and Mercaptopropionyalkali with a pH-cleavable hydrozone bond. Using a Michael addition reaction, several Dox-containing thiol moieties were grafted onto the surface of the PDA. The drug loading capacity can reach 35.43%. It can minimize the metabolic problem of silica. The released behavior of Dox can be significantly enhanced at endosomal pH compared to physiological pH. After folate modification, nanoparticles can lead to more cellular endocytosis. Meanwhile animal assays showed that more Dox accumulated in tumor tissue, which can enhanced the cytotoxicity to 4T1 cancer cells with a targeting group compared to free DOX and untargeted groups. Meanwhile, the tumor growth was significantly inhibited. This promising material shows a promising future as a drug delivery system.

Revealing the Roles of Solvation in D-mannitol’s Polymorphic Nucleation

There has been much interest in the role of solution chemistry in determining the polymorphic formation of organic crystals. For convenience, the predominantly investigated systems are those that contain distinct building blocks among the polymorphs; in this work, an important drug excipient, D-mannitol (D-man), was selected as a case study, which represents a polymorphic system that only has the same building blocks. By employing the Hirshfeld surface analysis and molecular dynamics (MD) simulations, D-mans crystal packing and the solvation nature in different solvents were studied on the molecular level. The results suggest that there is a direct link between the solution speciation and crystal structure, and two distinct solvation modes were identified along with their impacts on nucleation. This study indicates the significant role of solvation in determining D-mans nucleation and offers new insights into the research on systems that do not have distinct building blocks among the polymorphs.

Polymorphs of daidzein and intermolecular interaction effect on solution crystallization

Daidzein (DAID), known as a phytoestrogen, is an important bioactive flavonoid isolated from soybean and pueraria. However, its poor solubility and low dissolution rate limit its clinical application. With the aim of finding a form with fit-for-purpose physicochemical properties, a comprehensive solid-state screening experiment was performed. As a result, three polymorphs were discovered and the single crystal structure of stable form II was revealed for the first time. Form II was obtained in solvents with high β and π* values, while form III was produced under opposite conditions. To clarify this phenomenon, intermolecular interactions were investigated through single crystal structure analysis, solvent property analysis and computational methods. The results demonstrated that the compact arrangement of DAID and the solvents used played a critical role in solution crystallization. Moreover, the physicochemical properties of these three polymorphs were fully characterized, and the powder dissolution behavior was determined in pure water and pH 1.2 and pH 6.8 buffer solutions. The newly discovered form II exhibited better thermal stability, lower moisture sorption and faster dissolution rate compared with the other forms.