A nonionic microemulsion co-loaded with atorvastatin and quercetin: Simultaneous spectroscopic analysis and payload release kinetics.

In this study, we have co-loadedatorvastatin (ATR) and quercetin (QCT) in a nonionic microemulsion. After developing a derivative ratio spectrophotometric technique for simultaneous analysis of ATR and QCT, pseudoternary phase diagram was constructed utilizing1:4 d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and ethanol as surfactant and cosurfactant, respectively. Oleic acid was used as oil phase. Structural characterization of the formulation was carried out along a water dilution line created in monophasic region. Characterizations at these dilution points were performed using dynamic light scattering and polarized light microscopy. The average hydrodynamic size of the optimized formulation was found to be 18.9 nm and it did not change upon loading of ATR and QCT. In vitro release was assessed for the formulations loaded with different ratios of ATR and QCT, and the data were fitted to different mathematical models. Interestingly, we noticed differences in release kinetics during changes in dose ratios, particularly for QCT. Higuchi kinetics, observed at equal dose, shifted to Korsmeyer-Peppas model at higher QCT-ATR ratio (2:1 and 4:1). This difference is attributable to the ability of QCT molecules of overwhelming the interface at higher concentrations. Altogether, our observations highlight that the ratio of payloads should be selected carefully in order to avoid unpredictable release patterns.

Sugar-based Cryoprotectants Stabilize Liposomal Vesicles by Exhibiting a Cholesterol-like Effect.

Liposomal vesicles tend to fuse and aggregate during lyophilization. To avoid these events, cryoprotectants are added to the dispersion before lyophilization. Herein, we have compared the effect of three commonly used cryoprotectants (mannitol, MTL; trehalose, THL; and ß-cyclodextrin, ß-CD) upon structural characteristics of liposomes. The formulation was prepared using ethanol injection method, and cryoprotectants were tested at three dose levels (2, 6, and 10 mM). We have elucidated their effect on soy lecithin (SL) liposomes formulated with and without cholesterol (CHL). Characterizations were performed using scattering, thermal, and spectroscopic techniques. CHL molecules interacted hydrophobically with the SL bilayer. In spite of triggering a noticeable increase in the hydrodynamic diameter (about 30 nm), CHL promoted the stabilization of vesicles. Hydrogen bonding interactions were verified by the shift in -OH stretching over 3300-3500 cm-1. This manifested in an increased phase transition temperature (Tm) of SL liposomes. Tm increased further upon incorporation of cryoprotectants, particularly with ß-CD. Enthalpic changes were indicative of an affinity interaction between phospholipids and cryoprotectants, regardless of the presence of CHL. ß-CD showed concentration-dependent changes in the energetics of this interaction. The affinity of cryoprotectant-liposome interaction has been ranked as ß-CD ≫ THL > MNT.

Effect of stoichiometry upon the characteristics of quercetin-arginine cocrystals formulated through solution crystallization.

OBJECTIVE: The aim of this study is to demonstrate the effect of stoichiometry upon characteristics of quercetin-arginine (QCT-Arg) cocrystals. SIGNIFICANCE: Quercetin (QCT) is a most abundant flavonoid in vegetables and fruits and has been widely used as an antioxidant. However, its oral bioavailability remains low due to poor aqueous solubility. We illustrate that QCT-Arg cocrystals formulated through an optimized stoichiometry can be a useful approach for its solubilization. METHOD: Cocrystals were prepared using solvent evaporation method. Characterizations were performed through microscopic, spectroscopic, and thermal techniques. The stoichiometry was confirmed from the binary phase diagram which was prepared using thermograms derived from differential scanning calorimetric experiments. RESULT: Cocrystal formation was accompanied by the conversion of isotropic phase into anisotropic one. Thread-like cocrystals were formed, regardless of QCT-Arg stoichiometry and solvent's polarity. Spectral analyses suggested that cocrystal structure was held together by hydrogen bonding between QCT and Arg. We ruled out the existence of eutectic mixture based on the observation of two eutectic points in the binary phase diagram. CONCLUSION: Morphology of cocrystals remained unaffected by the solvent type, stoichiometry and the presence of surfactant. We noticed that the cocrystals could improve the aqueous solubility of QCT.

Recent Updates on Applications of Lipid-Based Nanoparticles for Site- Specific Drug Delivery.

BACKGROUND: Site-specific drug delivery is a widespread and demanding area nowadays. Lipid-based nanoparticulate drug delivery systems have shown promising effects for targeting drugs among lymphatic systems, brain tissues, lungs, and skin. Recently, lipid nanoparticles have been used for targeting the brain via the mucosal route for local therapeutic effects. Lipid nanoparticles (LNPs) can help in enhancing the efficacy and lowering the toxicities of anticancer drugs to treat the tumors, particularly in lymph after metastases of tumors. LNPs contain a nonpolar core that can improve the absorption of lipophilic drugs into the lymph node and treat tumors. Cellular uptake of drugs can also be enhanced using LNPs and therefore, LNPs are the ideal carrier for treating intracellular infections, such as leishmaniasis, tuberculosis and parasitic infection in the brain, etc. Furthermore, specific surface modifications with molecules like mannose, or PEG could improve the macrophage uptake and hence effectively eradicate parasites hiding in macrophages. METHODS: An electronic literature search was conducted to update the advancements in the field of site-specific drug delivery utilizing lipid-based nanoparticles. A search of the Scopus database (https://www.scopus.com/home.uri) was conducted using the following keywords: lipid-based nanoparticles; site-specific delivery. CONCLUSION: Solid lipid nanoparticles have shown site-specific targeted delivery to various organs including the liver, oral mucosa, brain, epidermis, pulmonary and lymphatic systems. These lipidbased systems showed improved bioavailability as well as reduced side effects. Therefore, the focus of this article is to review the recent research studies on LNPs for site-specific or targeting drug delivery.