Scheme 1. A) Preparation of DTF-FFP NPs. B) Upon accumulation at the bacterial inflammatory site, both fluorescence and photosensitization of DTF-FFP NPs were activated by HClO microenvironment produced by phagocyte to effectively image and ablate the bacteria inside invaded phagocytes.
The malignancy of colorectal cancer (CRC) is connected with inflammation and tumor-associated macrophages (TAMs), but effective therapeutics for CRC are limited. To integrate therapeutic targeting with tumor microenvironment (TME) reprogramming, here we develop biocompatible, non-covalent channel-type nanoparticles (CNPs) that are fabricated through host-guest complexation and self-assemble of mannose-modified γ-cyclodextrin (M-γ-CD) with Regorafenib (RG), RG@M-γ-CD CNPs. In addition to its carrier role, M-γ-CD serves as a targeting device and participates in TME regulation. RG@M-γ-CD CNPs attenuate inflammation and inhibit TAM activation by targeting macrophages. They also improve RG’s anti-tumor effect by potentiating kinase suppression. In vivo application shows that the channel-type formulation optimizes the pharmacokinetics and bio-distribution of RG. In colitis-associated cancer and CT26 mouse models, RG@M-γ-CD is proven to be a targeted, safe and effective anti-tumor nanomedicine that suppresses tumor cell proliferation, lesions neovascularization, and remodels TME. These findings indicate RG@M-γ-CD CNPs as a potential strategy for CRC treatment.
The dissolution rate is the rate-limiting step for Biopharmaceutics Classification System (BCS) class II drugs to enhance their in vivo pharmacokinetic behaviors. There are some factors affecting the dissolution rate, such as polymorphism, particle size, and crystal habit. In this study, to improve the dissolution rate and enhance the in vivo pharmacokinetics of sorafenib tosylate (Sor-Tos), a BCS class II drug, two crystal habits of Sor-Tos were prepared. A plate-shaped crystal habit (ST-A) and a needle-shaped crystal habit (ST-B) were harvested by recrystallization from acetone (ACN) and n-butanol (BuOH), respectively. The surface chemistry of the two crystal habits was determined by powder X-ray diffraction (PXRD) data, molecular modeling, and face indexation analysis, and confirmed by X-ray photoelectron spectroscopy (XPS) data. The results showed that ST-B had a larger hydrophilic surface than ST-A, and subsequently a higher dissolution rate and a substantial enhancement of the in vivo pharmacokinetic performance of ST-B.
Two new co-crystals, Ticagrelor with Nicotinamide, have been prepared with improved solubility. Because Ticalegor has a poor solubility and dissolution rate, a novel co-crystallization method with structurally homogenous crystalline material, an active pharmaceutical ingredient (API), and co-former indefinite stoichiometric amount has been made to improve Ticagrelor’s solubility. The co-crystal of Ticagrelor (TICA) with Nicotinamide (NCA) was prepared in ratio (1:1) and confirmed by FTIR, DSC, and XRD characterization. Furthermore, the single crystal structure of TICA-NCA hydrate was analyzed. The solubility of co-crystals was investigated in pH 2 acidic medium, which was a significant improvement as compared to the solubility of a free drug. The in vitro dissolution rate of co-crystal was larger than that of the commercial product.
Drugs with poor biopharmaceutical performance are the main obstacle to the development and design of medicinal preparations. The anisotropic surface chemistry of different surfaces on the crystal influences its physical and chemical properties, such as solubility, tableting, etc. In this study, the antisolvent crystallization and rapid-cooling crystallization were carried out to tune the crystal habits of ticagrelor (TICA) form II. Different crystal habits of ticagrelor (TICA) form II (TICA-A, TICA-B, TICA-C, TICA-D, and TICA-E) were prepared and evaluated for solubility. The single-crystal diffraction (SXRD) indicated that TICA form II belongs to the triclinic P1 space group with four TICA molecules in the asymmetric unit. The TICA molecules are generated through intermolecular hydrogen bonds along the (010) direction, forming an infinite molecular chain, which are further stacked by hydrogen bonds between hydroxyethoxy side chains, forming molecular circles composed of six TICA molecules along bc directions. Thus, in the case of TICA form II, hydrogen bonds drive growth along one axis (b-axis), which results in the formation of mostly needle-shape crystals. Morphology and face indexation reveals that (001), (010) and (01-1) are the main crystal planes. Powder diffractions showed that five habits have the same crystal structure and different relative intensity of diffraction peak. The solubility of the obtained crystals showed the crystal habits affect their solubility. This work is helpful for studying the mechanism of crystal habit modification and its effect on solubility.Crystals 2019, 9, 556 2 of 15 such as crystal habit, polymorphism and reduction of the particle size [15][16][17][18][19][20]. There have been many studies demonstrating the effect of polymorphism on oral bioavailability and/or dissolution rate [21]. However, the dissolution rate not only differs for different polymorphisms, but also, for different crystal habits [22], which has received scant attention. Meanwhile, crystal habits also influence stability, flowability, suspension, packing, density, compaction, etc. [23][24][25][26][27]. Thus, optimizing crystal properties by modification of the crystal habit of a drug seems to offer an alternative approach to changing the bioavailability of drugs. The relative growth rate of each surface determines the overall shape of the crystal. The growth rate of the crystal surface will be controlled by a combination of structure-related factors, such as dislocations and intermolecular bonds, and by exterior factors such as solvents, rate of agitation, additives, temperature, etc. [28][29][30][31][32][33][34][35].This study aims to systematically investigate how crystal behavior affects the ticagrelor's solubility. TICA form II (TICA-II) with different crystal habits were prepared by controlling the crystallization process. To systematically investigate the relationship between crystal habit and orientation of the molecules of TICA form II in the crystal lattice, single crystals were obtained, and the cr...
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