Growth mechanisms of amorphous nanoparticles in solution and during heat drying.

The purpose of this study was twofold: to identify the growth mechanisms of amorphous nanoparticles in solution and during the drying process at high temperatures, and to guide the process condition and stabilizer selection for amorphous nanoparticle formulations. In contrast to nanocrystals that are mostly mechanically robust, amorphous nanoparticles tend to undergo deformation under stress. As a result, development of a stable formulation and evaluation of the drying process for re-dispersible amorphous nanoparticles presents considerable challenges. Although amorphous nanoparticles have stability issues, they have several pros in terms of production, high monodispersity, and diverse applications in drug delivery. In this study, amorphous nanoparticles were prepared via liquid-liquid phase separation, and their growth mechanisms were investigated both in solution and during the drying process. In solution, particles were found to be susceptible to flocculation, crystallization, coalescence, and Ostwald ripening, with coalescence being a preliminary step providing the driving force for Ostwald ripening. However, during the heat drying process, coalescence and crystallization were found to be the primary mechanisms for particle growth, with Ostwald ripening being negligible due to reduced molecular mobility. The glass transition temperature (Tg) of these amorphous nanoparticles was found to be a crucial factor both in solution and during the drying process. At temperatures < Tg, particles remained in a rigid, glassy state thereby inhibiting coalescence, whereas at or above Tg, particles transition from glassy to rubbery state, making them more susceptible to deformation and coalescence. The mechanistic understanding of particle growth from this study can also be extended to the stabilization of other types of soft nanoparticles.

Complex oiling-out behavior of procaine with stable and metastable liquid phases.

During the crystallization of a solute from solvent(s), spontaneous liquid-liquid phase separation (LLPS) might occur, under certain conditions. This phenomenon, colloquially referred to as "oiling-out" in the pharmaceutical industry, often leads to undesired outcomes, including undesired particle properties, encrustation, ineffective impurity rejection, and excessively long process time. Therefore, it is critical to understand the thermodynamic driving force and phase boundaries of this phenomenon, such that rational strategies can be developed to avoid oiling-out or minimize its negative impact. In this study, we systematically evaluated the oiling-out behavior of procaine, a low melting point drug, in the solvent systems heptane, and ethanol-heptane as a function of temperature and solvent composition. In the procaine-heptane binary system, we observed a region where the LLPS is metastable with respect to crystallization, which is most commonly observed in the crystallization of modern active pharmaceutical ingredients (APIs); however, we also identified a region of the phase diagram where the LLPS is stable with respect to crystallization, and therefore will persist indefinitely. In the procaine-ethanol-heptane ternary system we identified five different regions, including a homogeneous liquid (L) region, two solid-liquid (SLI and SLII) regions, a liquid-liquid (LILII) region, and a solid-liquid-liquid (SLILII) region. The binary and ternary phase diagrams were also predicted using a state-of-the-art thermodynamic model: the SAFT-γ-Mie equation of state, and the results were compared with experimental data. Our findings highlight the complexity of oiling-out behavior. This work also represents a combined modeling and experimental platform to identify phase boundaries that will enable rational selection of strategies to crystallize active pharmaceutical ingredients with oiling-out risks.

Enhanced delivery of the phototherapeutic nanoparticles via hepatocyte overload.

Phototherapeutic nanoparticles (NPs) were prepared with methylene blue (MB), indocyanine green (ICG), and Solutol through self-assembly. Generation of reactive oxygen species and elevation of temperature were observed that verify the photodynamic/photothermal effects of the NPs. Morphology and size distribution of the NPs were examined by transmittance electron microscopy and dynamic light scattering. The biodistribution of the NPs and their antitumor efficacy were examined using tumor-bearing mice to understand the phototherapeutic effect of the NPs on tumors. To enhance targetability with enhanced therapeutic efficacy, empty NPs (Solutol nanoparticles without MB and ICG) at different concentrations were injected along with the phototherapeutic NPs. Enhanced delivery of the phototherapeutic NPs at the tumor site was examined based on hepatocyte overload.

Influence of Panax ginseng formulation on skin microbiota: A randomized, split face comparative clinical study.

Background: Skin microbiota is important for maintenance of skin homeostasis; however, its disturbance may cause an increase in pathogenic microorganisms. Therefore, we aimed to develop a red ginseng formulation that can selectively promote beneficial bacteria. Methods: The effects of red ginseng formulation on microorganism growth were analyzed by comparing the growth rates of Staphylococcus aureus, S. epidermidis, and Cutibacterium acnes. Various preservatives mixed with red ginseng formulation were evaluated to determine the ideal composition for selective growth promotion of S. epidermidis. Red ginseng formulation with selected preservative was loaded into a biocompatible polymer mixture and applied to the faces of 20 female subjects in the clinical trial to observe changes in the skin microbiome. Results: Red ginseng formulation promoted the growth of S. aureus and S. epidermidis compared to fructooligosaccharide. When 1,2-hexanediol was applied with red ginseng formulation, only S. epidermidis showed selective growth. The analysis of the release rates of ginsenoside-Rg1 and -Re revealed that the exact content of Pluronic F-127 was around 11%. The application of hydrogel resulted in a decrease in C. acnes in all subjects. In subjects with low levels of S. epidermidis, the distribution of S. epidermidis was significantly increased with the application of hydrogel formulation and total microbial species of subjects decreased by 50% during the clinical trial. Conclusion: We confirmed that red ginseng formulation with 1,2-hexanediol can help maintain skin homeostasis through improvement of skin microbiome.

Pluronics: Intelligent building units for targeted cancer therapy and molecular imaging.

Pluronics are triblock copolymers, in which two hydrophilic poly (ethylene oxide) (PEO) blocks are connected via a hydrophobic poly propylene oxide (PPO) block. Because of their low molecular weight and high content of PEO, Pluronics have demonstrated the micellization phenomenon, which is dependent on temperature and/or concentration. With an understanding of micellization phenomenon in more detail, information on the morphology, micelle core radius, aggregation behavior with critical micelle concentration (CMC) and critical micelle temperature (CMT) and so on has been revealed. Based on this acquired information, various studies have been performed for biomedical applications such as drug delivery systems, tissue regeneration scaffolders, and biosurfactants. This review discusses the delivery of small molecules and macromolecules using Pluronic-based NPs and their composites.

Paenibacillus swuensis sp. nov., a bacterium isolated from soil.

Strain DY6(T), a Gram-positive endospore-forming motile rod-shaped bacterium, was isolated from soil in South Korea and characterized to determine its taxonomic position. Phylogenetic analyses based on the 16S rRNA gene sequence of strain DY6(T) revealed that strain DY6(T) belongs to the genus Paenibacillus in the family Paenibacillaceae in the class Bacilli. The highest degree of sequence similarities of strain DY6(T) were found with Paenibacillus gansuensis B518(T) (97.9%), P. chitinolyticus IFO 15660(T) (95.3%), P. chinjuensis WN9T (94.7%), and P. rigui WPCB173(T) (94.7%). Chemotaxonomic data revealed that the predominant fatty acids were anteiso-C(15:0) (38.7%) and C(16:0) (18.0%). A complex polar lipid profile consisted of major amounts of diphosphatidylglycerol, phosphatidylethanolamine, and phosphatidylglycerol. The predominant respiratory quinone was MK-7. Based on these phylogenetic, chemotaxonomic, and phenotypic data, strain DY6(T) (=KCTC 33026(T) =JCM 18491(T)) should be classified as a type strain of a novel species, for which the name Paenibacillus swuensis sp. nov. is proposed.