Synthon Approach in Crystal Engineering to Modulate Physicochemical Properties in Organic Salts of Chlorpropamide.

The formulation of drug with improved bioavailability is always challenging and indispensable in the field of pharmaceutics. The control of intermolecular interactions via crystal engineering approach and solid-state molecular recognition results in the formation of active drug molecules with modulated pharmacological benefits. Therefore, with the aim to improve the solubility and dissolution rate of the drug chlorpropamide (CPA), the mechanochemical liquid-assisted grinding (LAG) of the drug with several pharmaceutically accepted excipients was performed. This contributed to the discovery of six novel solid phases, namely salts, salt cocrystals and salt cocrystal hydrate─the salt of CPA with 3, 4-diaminopyridine (DAP); salt and salt cocrystal (SC) polymorph (Z″=3) with 1, 4-diazabicyclo [2.2.2] octane (DABCO); a salt, SC polymorph (Z″=9), and a SC hydrate (Z″=9) with piperazine (PIP). The formation of these salts and salt cocrystals are mainly guided by the strong hydrogen bonds with tunable strength having high electrostatic contribution. This attractive interaction brings the donor and the acceptor atoms close to each other for a facile proton transfer. Furthermore, the conformational constraints on the drug molecules, provided by the excipients via strong and directional hydrogen bonds, are quite impressive as this leads to the identification and characterization of "new conformational isomers" for the CPA molecules. The new crystalline phases exhibit enhanced intrinsic dissolution rate in comparison to that of the pure drug, the magnitude being 7, 131, and 120 folds for CPADAP, CPADABCO_II, and CPAPIP_III, respectively. Furthermore, it is interesting to note that the order of solubility is enhanced by 2.7-, 3-, and 7-fold, respectively, for the abovementioned salts. This also mirrors the trends in the magnitude of the binding energy, the higher magnitude being reflected in the lower solubility. Additionally, the in vivo experiments performed in SD rats results in the enhancement of the magnitude of the pharmacokinetic properties, when compared to the pristine drug. The concentration of the drug in CPADABCO_II and CPAPIP_III formulations exhibits 6- and 4-fold increments, respectively. Indeed, these results corroborate to the trends observed in the structural characterization, intermolecular energy calculations, solubility, and in vitro dissolution assessments.

Biocompatible polymer-coated magneto-fluorescent super nanoparticles for the homing of mesenchymal stem cells.

Stem cell plays an important role in the clinical field. However, the effective delivery of stem cells to the targeted site relies on the efficient homing of the cells to the site of injury. In view of that, fluorescent magnetic nanoparticles stick out due to their wide range of enabling functions including cellular homing and tracking. The present study unravels the synthesis of polymer-coated biocompatible and fluorescent magnetic nanoparticles (FMNPs) by a single-step hydrothermal synthesis method. Importantly, the facile method developed the biological super nanoparticles consisting of the magnetic core, which is surrounded by the fluorescent nanodot-decorated polymeric shell. The synthesized particles showed an amorphous nature, and superparamagnetic properties, with efficient fluorescence properties of emission at the blue range (Ì´ 410 nm). The FMNP labeling showed the mesenchymal stem cell (MSC) homing to the desired site in the presence of an external magnetic field. The in-house synthesized nanoparticles showed significant cytocompatibility and hemocompatibility in vitro as well as in vivo conditions owing to their surface coating. This unprecedented work advances the efficient internalization of FMNPs in MSCs and their enhanced migration potential provides a breakthrough in stem cell delivery for therapeutic applications. STATEMENT OF SIGNIFICANCE: The bi-modal fluorescent magnetic nanoparticles hold a promising role in the biomedical field for mesenchymal stem cell homing and tracking. Hence, in this study, for the first time, we have synthesized the fluorescent magnetic nanoparticle with polymer coating via an easy single-step method. The nanoparticle with a polymer coat enhanced the biocompatibility and effortless internalization of the nanoparticle into mesenchymal stem cells without hampering the native stem cell properties. Furthermore, the enhanced migration potential of such magnetized stem cells and their homing at the target site by applying an external magnetic field opened up avenues for the smart delivery of mesenchymal stem cells at complex sites such as retina for the tissue regeneration.