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Myricetin (MYR) was incorporated into pH-sensitive liposomes in order to improve its bioavailability and anti-hyperuricemic activity. The MYR pH-sensitive liposomes (MYR liposomes) were prepared using thin film dispersion method, and assessed by particle size (PS), polydispersed index (PDI), zeta potential (ZP), encapsulation efficiency, drug loading, and in vitro release rate. Pharmacokinetics and anti-hyperuricemic activities were also evaluated. The PS, PDI, ZP, encapsulation efficiency, and drug loading of MYR liposomes were 184.34 ± 1.05 nm, 0.215 ± 0.005, −38.46 ± 0.30 mV, 83.42 ± 1.07%w/w, and 6.20 ± 0.31%w/w, respectively. The release rate of MYR liposomes was higher than free MYR, wherein the cumulative value responded to pH. Besides, the Cmax of MYR liposomes was 4.92 ± 0.20 μg/mL. The level of uric acid in the M-L-H group (200 mg/kg) was reduced by 54.74%w/v in comparison with the model group. MYR liposomes exhibited pH sensitivity and could potentially enhance the oral bioavailability and anti-hyperuricemic efficacy of MYR. [ABSTRACT FROM AUTHOR]

Encapsulation of esculetin into DSPE-MPEG2000 carrier was performed to improve its water solubility and oral bioavailability, as well as enhance its anti-inflammatory effect on a mouse model of ulcerative colitis that was induced with dextran sulphate sodium (DSS). We determined the in-vitro and in-vivo high-performance liquid chromatographic (HPLC) analysis method of esculetin; Esculetin-loaded nanostructure lipid carrier (Esc-NLC) was prepared using a thin-film dispersion method, wherein a particle size analyser was used to measure the particle size (PS) and zeta potential (ZP) of the Esc-NLC, while a transmission electron microscope (TEM) was employed to observe its morphology. Also, HPLC was used to measure its drug loading (DL), encapsulation efficiency (EE) and the in-vitro release of the preparation, as well as investigate the pharmacokinetic parameters. In addition, its anti-colitis effect was evaluated via histopathological examination of HE-stained sections and detection of the concentrations of tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1 beta (β), and IL-6 in serum with ELISA kits. The PS of Esc-NLC was 102.29 ± 0.63 nm with relative standard deviation (RSD) of 1.08% (with poly-dispersity index-PDI of 0.197 ± 0.023), while the ZP was −15.67 ± 1.39 mV with RSD of 1.24%. Solubility of esculetin was improved coupled with prolonged release time. Its pharmacokinetic parameters were compared with that of free esculetin, wherein the maximum concentration of the drug in plasma was increased by 5.5 times. Of note, bioavailability of the drug was increased by 1.7 times, while the half-life was prolonged by 2.4 times. In the anti-colitis efficacy experiment, the mice in Esc and Esc-NLC groups exhibited significantly reduced levels of TNF-α, IL-1β, and IL-6 in their sera comparable to the DSS group. Colon histopathological examination revealed that mice with ulcerative colitis in both Esc and Esc-NLC groups displayed improved inflammation, amid the Esc-NLC groups having the best prophylactic treatment effect. Esc-NLC could ameliorate DSS-induced ulcerative colitis by improving bioavailability, prolonging drug release time and regulating cytokine release. This observation confirmed the potential of Esc-NLC to reduce inflammation in ulcerative colitis, albeit the need for follow-up research to verify the application of this strategy to clinical treatment of ulcerative colitis. [ABSTRACT FROM AUTHOR]

To prepare polyethylene glycol succinate-vitamin E modified pinocembrin (PCB)-loaded liposomes (PCBT-liposomes) and evaluate PCBT-liposomal pharmacokinetics and antihyperglycemic activity. The novel PCBT-liposomes demonstrated a promising application prospect as a nano drug carrier for future research. Thin film dispersion was used to prepare PCBT-liposomes. We measured a series of characterization, followed by in vitro cumulative release, in vivo pharmacokinetic study, and antihyperglycemic activity evaluation. PCBT-liposomes displayed spherical and bilayered nanoparticles with mean particle size (roughly 92 nm), negative zeta potential (about −26.650 mV), high drug encapsulation efficiency (87.32 ± 1.34%) and good storage (at 4 or 25 °C) stability during 48 h after hydration. The cumulative release rate of PCBT-liposomes was markedly higher than free PCB in four different pH media. In vivo investigation showed that PCBT-liposomes could obviously improve oral bioavailability of PCB by 1.96 times, whereas the Cmax, MRT0–t, and T1/2 of PCBT-liposomes were roughly 1.700 ± 0.139 µg·mL−1, 12.695 ± 1.647 h, and 14.244 h, respectively. In terms of biochemical analysis, aspartate amino-transferase (AST), alanine amino-transferase (ALT), interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α) concentrations in serum of diabetic mice were respectively decreased 28.28%, 17.23%, 17.77%, and 8.08% after PCBT-liposomal treatment. These results show PCBT-liposomal preparation as an excellent nano-carrier which has the potential to improve water solubility, bioavailability, and antihyperglycemic activity of PCB, amid broadening the application of PCB in the clinical settings. [ABSTRACT FROM AUTHOR]

Hyperoside (Hyp) self-assembled polymeric micelles (Hyp-PMs) were purposely developed to enhance aqueous solubility, in vivo availability and anti-oxidative effect of Hyp. In preparing Hyp-PMs, we employed the thin film dispersion method with the micelles consisting of TPGs and mPEG2000-PDLLA3000. The particle size, polydispersity index and zeta potential of Hyp-PMs were 67.42 ± 1.44 nm, 0.229 ± 0.015 and −18.67 ± 0.576 mV, respectively, coupled with high encapsulation efficiency （EE）of 90.63 ± 1.45% and drug loading (DL) of 6.97 ± 1.56%. Furthermore, the value of critical micelle concentration (CMC) was quite low, which indicated good stability and improved self-assembly ability of Hyp-PMs. Also, trend of in vitro Hyp release from Hyp-PMs demonstrated enhanced solubility of Hyp. Similarly, in comparison with free Hyp, oral bioavailability of Hyp-PMs was improved (about 8 folds) whilst half-life of Hyp-PMs was extended (about 3 folds). In vitro anti-oxidative effect showed obvious strong scavenging DPPH capability of Hyp-PMs, which may be attributed to its smaller size and better solubility. Altogether, Hyp-PMs may serve as a possible strategy to potentially enhance aqueous solubility, bioavailability and anti-oxidative effect of Hyp, which may play a key role in Hyp application in the pharmaceutical industries. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop licochalcone A-loaded self-microemulsifying drug delivery system (LCA-SMEDDS) to improve bioavailability and anti-hyperuricemic activity of hydrophobic natural compound licochalcone A (LCA). The prepared LCA-SMEDDS was characterised by transmission electron microscopy analysis, particle size, polymer dispersity index (PDI), zeta potential, stability tests and in vitro release analysis. LCA-SMEDDS and free LCA were orally administered to Sprague-Dawley rats to investigate respective bioavailability. The hyperuricaemia rat model was established to evaluate anti-hyperuricemic activity. The particle size, PDI, and zeta potential of LCA-SMEDDS were 25.68 ± 0.79 nm, 0.074 ± 0.024, −14.37 ± 2.17 mV. The oral bioavailability of LCA-SMEDDS was increased 2.36-fold compared with the free LCA. The uric acid level of LCA-SMEDDS group (200 mg/kg) was decreased 60.08% compared with model control group. The developed LCA-SMEDDS could be an outstanding candidate for improving oral bioavailability and anti-hyperuricemic activity of LCA. [ABSTRACT FROM AUTHOR]

6-Gingerol, an active herbal ingredient of ginger has various bioactivities such as anti-neurodegenerative disease, anti-inflammatory and so on. The aim of the present study was to enhance the oral bioavailability and brain distribution of 6-Gingerol via polymeric micelles. A polymeric micelles drug delivery system of 6-Gingerol consisting of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and Poly (ethylene glycol)-poly (ε-caprolactone) (PEG-PCL) was prepared via solvent injection method. The developed 6-Gingerol-loaded TPGS/PEG-PCL micelles (6-GTPMs) were characterized based on particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), drug loading (DL) and in vitro release profile. The pharmacokinetics and tissue distribution studies were also evaluated. The nanoformulation produced a particle size of 73.24 ± 2.84 nm with acceptable PDI (0.129 ± 0.03), zeta potential (−2.74 ± 0.92 mV), DL (4.64%) and EE (79.68%). The in vitro release profile showed that the 6-GTPMs enhanced the solubility of 6-Gingerol, while the pharmaceutical analysis in rats indicated that 6-GTPMs significantly improved the oral bioavailability of 6-Gingerol (about 3 folds) in circulation. The 6-GTPMs exhibited remarkable brain targetability in the tissue distribution analysis. Collectively, a 6-Gingerol polymeric micelle with enhanced oral bioavailability coupled with excellent brain distribution was successfully developed. [ABSTRACT FROM AUTHOR]

Isoliquiritigenin (ISL) possesses a variety of pharmacological activities amid poor solubility in water which has restricted its clinical application. In this study, isoliquiritigenin-loaded F127/P123 polymeric micelles (ISL-FPM) were successfully prepared and evaluated in vitro and in vivo. The particle size, polydispersity index, and zeta potential of the selected formulation were 20.12 ± 0.72 nm, 0.183 ± 0.046, and −38.31 ± 0.33 mV, respectively, coupled with high encapsulation efficiency of 93.76 ± 0.31%. Drug-loading test showed the solubility of ISL after formulating into micelles was 232 times higher than its intrinsic solubility. Moreover, critical micelle concentration (CMC) was tested with fluorescence probe method and turned out to be quite low, which implied high stability of ISL-FPM. Release profile in HCl (pH 1.2), double distilled water, and PBS (pH 7.4) of ISL-FPM reached over 80%, while free ISL was around 40%. Pharmacokinetic research revealed that formulated ISL-FPM significantly increased bioavailability by nearly 2.23-fold compared to free ISL. According to the results of in vitro antioxidant activity, scavenging DPPH activity of ISL was significantly strengthened when it was loaded into polymeric micelles. Altogether, ISL-FPM can act as a promising approach to improve solubility as well as enhance bioavailability and antioxidant activity of ISL. [ABSTRACT FROM AUTHOR]