Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Pharm Dev Technol ; : 1-8, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32009511

RESUMO

Piperine (Pip) has been widely studied for its multiple activities such as antidepressant, anti-epileptic, and so forth. However, the poor water solubility coupled with low bioavailability may inevitably hinder the application of Pip in the clinical setting. In this study, a formulation strategy was proposed to spontaneously resolve the low bioavailability and dose dividing issue of Pip. The matrix pellets (Pip-SR-pellets) consisting of Pip solid dispersion (Pip-SD) and hydroxypropylmethyl cellulose-K100 were developed to achieve an increased and sustained release profile in vitro. The Pip-SR-pellets were compacted into fast disintegrating tablets (FDTs) with a blend of excipients comprising lactose, MCC, LS-HPC, and CMS-Na. The Pip-SD was characterized by solubility study and XRD. The evaluation of the cross-sectional morphology of the Pip-FDTs via scanning electron microscope proved that Pip-SR-pellets maintained its structural integrity during compression and were uniformly distributed in the Pip-FDTs. The release profile of Pip-SR-pellets was highly consistent with the Pip-FDTs. In vivo pharmacokinetics study demonstrated that the relative bioavailability of Pip-SR-pellets was approximately 2.70-fold higher than that of the pure drug, and 1.62-fold compared with that of Pip-SD. This work therefore showed a potential industrialized method could be applied to formulate poorly water-soluble drug that has dose-dividing requirement.

2.
Food Chem Toxicol ; 137: 111126, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31954714

RESUMO

Syringic acid (SA), a natural polyphenol found in fruits and vegetables, is claimed to show notable hepatoprotection. Nevertheless, low solubility and bioavailability hamper the application of SA. This study aimed to investigate the potential of TPGS/F127/F68 mixed polymeric micelles as a sustained and liver-targeting nanocarrier for SA. Herein, the prepared SA-loaded TPGS/F127/F68 mixed polymeric micelles (SA-TPGS-Ms) were spherically-shaped and homogeneously-distributed nanoparticles with high entrapment efficiency (94.67 ± 2.05%) and sustained release. Besides, in-vitro cell culture studies revealed that SA-TPGS-Ms substantially promoted cellular uptake with excellent biocompatibility. After oral administration, SA-TPGS-Ms demonstrated an increased bioavailability (2.3-fold) and delayed in-vivo elimination compared with the free SA. Furthermore, the alleviation of oxidative stress and amelioration of hepatic injury in CCl4-induced hepatotoxicity mice further demonstrated the excellent hepatoprotection of SA-TPGS-Ms. Collectively, SA-TPGS-Ms could be a promising nanocarrier for the utilization of SA in functional foods, with enhanced bioavailability and hepatoprotection.

3.
Int J Pharm ; 575: 118980, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31899320

RESUMO

Cardiac glycosides (CGs) have been used to treat cancer for hundreds of years. However, the narrow therapeutic window and system toxicity have hindered their wide clinical applications. Herein, the small molecule prodrug strategy and nanotechnology were integrated into one drug delivery system with enhanced therapeutic effect. Using periplocymarin (PPM) as a target agent, we designed a novel redox-responsive prodrug conjugated with linoleic acid (PPM-ss-LA), which was capable of self-assembling independent of exogenous excipients. This prodrug could co-assemble with DSPE2k to form PEGylated prodrug nanoparticles (PPM-ss-LA/DSPE2k-NPs) with enhanced colloidal stability and blood circulation. Compared with free PPM, PPM-ss-LA/DSPE2k-NPs retained high anti-proliferative activity and showed increased cell uptake and therapeutic efficacy. Furthermore, the PPM-ss-LA/DSPE2k-NPs acquired a greatly enhancement of 50% lethal dose (LD50) in mice and reduced system toxicity compared with the free drug. Overall, the on-demand release of nanoprodrug delivery system could improve the therapeutic window and anticancer efficacy of CGs.

4.
Int J Pharm ; 572: 118735, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31705971

RESUMO

Myricitrin has many pharmacological effects, such as anti-inflammation, liver protection and anti-oxidation. However, its clinical application is limited by poor solubility and low oral bioavailability. The preparation of myricitrin-loaded proliposomes (MPs) was achieved via the combination of thin-film dispersion technique and freeze-drying method. The in vitro release of MPs compared with free myricitrin was measured in different dissolution media while the pharmacokinetic study was also conducted in rats. Moreover, the uric acid-lowering activity of MPs was investigated in the hyperuricemic rat model. The prepared myricitrin appeared to be spherical. Notably, compared with the free myricitrin, the cumulative release in vitro and in vivo oral bioavailability of MPs were markedly increased. Besides, the MPs could significantly lower the serum uric acid level as well as ameliorate liver and kidney damage in hyperuricemic rats compared with the model group. Therefore, the present work supports the fact that MPs improved the oral bioavailability of myricitrin for the prospect of clinical application.

5.
AAPS PharmSciTech ; 20(7): 284, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31407165

RESUMO

This report aimed to formulate self-micro-emulsifying (SMEDDS) controlled-release pellets delivery system to improve aqueous solubility and in vivo availability of eugenol, a main constituent of clove oil with multiple pharmacological activities. The optimal formulation of eugenol-SMEDDS was eugenol: ethyl oleate: cremophor EL: 1, 2-propylene glycol at the ratio of 5:5:12:8. The SMEDDS were observed under transmission electron microscopy (TEM), and the size distribution was measured with dynamic laser light scatting (DLS). The particle size, index of dispersity (PDI), and zeta potential (Z-potential) were 68.8 ± 0.1 nm, 0.285 ± 0.031, and - 11.62 ± 0.63 mV, respectively. Eugenol-SMEDDS exhibited substantial increased in vitro dissolution compared with the free eugenol. The eugenol-SMEDDS sustained-release pellets (eugenol-SMEDDS-SR pellets) comprising of eugenol-SMEDDS, hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (MCC), and ethyl cellulose (EC) coats were obtained via extrusion spheronization technique. Consequently, the obtained pellets observed under scanning electron microscopy (SEM) showed spherical shape with smooth surface, desirable drug loading capacity (7.18 ± 0.17%), greater stability, and controlled release. Meanwhile, the oral test showed that bioavailability of eugenol in pellets was highly improved 23.6-fold to the free eugenol. Overall, these results suggested that the improvement of the oral bioavailability of eugenol-SMEDDS-SR could be due to the successful incorporation of the drug into SMEDDS.


Assuntos
Eugenol/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Celulose/análogos & derivados , Celulose/química , Química Farmacêutica/métodos , Preparações de Ação Retardada , Cães , Emulsões/química , Eugenol/administração & dosagem , Eugenol/química , Derivados da Hipromelose/química , Tamanho da Partícula , Polietilenoglicóis/química
6.
Fitoterapia ; 138: 104348, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31470062

RESUMO

Gastrodigenin rhamnopyranoside (GR) is a hepatoprotective compound that exists in Moringa oleifera seeds. However, the UPLC-MS/MS method for the determination of GR (in-vitro/in-vivo) is lacking clarification. Herein, this study established the UPLC-MS/MS technique, which was effective and sensitive for the investigation of the pharmacokinetics and biodistribution of GR in rats and mice. The separation was achieved with a Shim-pack XR-ODS III C18 column (2.0 × 75 mm, 1.6 µm) at 40 °C, while the mobile phase (Acetonitrile/0.1% Formic acid =12:82, v/v) was at an eluting rate of 0.2 mL/min. The Multiple Reaction Monitoring (MRM) was selected for quantification, i.e., m/z [M + HCOO]- 314.9 → 269 for GR and m/z [M + HCOO] - 182.85 → 137 for Tyrosol as the internal standard. The calibration curves were linearly ranged from 10 to 2500 ng/mL (r ≥ 0.999) with a lower-limit-of-quantification (LLOQ) of 10 ng/mL in the various biological samples (plasma, liver, heart, lung, spleen, brain, kidney). The intra- and inter-day precision was within 5%, while accuracy ranged from -11.4% - 8.33%. Recovery and matrix effect were with 80.32 to 101.31% and 90.36 to 103.76%, respectively, in a reasonable range. After oral and intravenous administration, GR was detected within 3 h but decreased rapidly in plasma, indicating fast elimination. Also, GR was quickly distributed in the various tissues, particularly in the kidney and spleen. The results demonstrated that the established UPLC-MS/MS method was highly linear, precise and accurate with the potential to be used for the quantitative analysis of GR in-vivo.


Assuntos
Glicosídeos/farmacocinética , Moringa/química , Sementes/química , Animais , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
7.
J Microencapsul ; 36(5): 500-512, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31347417

RESUMO

Aims: The aim was to improve the absorption and bioavailability of [6]-shogaol with ß-cyclodextrin (ß-CD) prior to in vitro and in vivo evaluation. Methods: [6]-Shogaol/ß-CDs inclusion complexes (6-S-ß-CDs) were developed using saturated aqueous solution method and characterised with appropriate techniques. The absorption and bioavailability potential of [6]-shogaol was evaluated via in vivo pharmacokinetics and in situ intestinal perfusion. Results: The results of characterisation showed that 6-S-ß-CDs (drug loading, 7.15%) were successfully formulated. In vitro release study indicated significantly improved [6]-shogaol release. Pharmacokinetic parameters such as Cmax, AUC0-36 h, and oral relative bioavailability (about 685.36%) were substantially enhanced. The in situ intestinal perfusion study revealed that [6]-shogaol was markedly absorbed via passive diffusion in the intestinal segments, and duodenum followed by ileum and jejunum. Conclusions: Cyclodextrin inclusion technology could enhance the intestinal absorption and oral bioavailability of hydrophobic drugs like [6]-shogaol.


Assuntos
Catecóis/administração & dosagem , Catecóis/farmacocinética , Portadores de Fármacos/química , Absorção Intestinal , beta-Ciclodextrinas/química , Animais , Disponibilidade Biológica , Gengibre/química , Mucosa Intestinal/metabolismo , Masculino , Ratos Sprague-Dawley
8.
AAPS PharmSciTech ; 20(5): 218, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31187334

RESUMO

The aim of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) for enhancement of the oral bioavailability of isoliquiritigenin (ISL) as well as evaluate its in vivo anti-hyperuricemic effect in rats. The ISL-loaded self-microemulsifying drug delivery system (ISL-SMEDDS) was comprised of ethyl oleate (EO, oil phase), Tween 80 (surfactant), and PEG 400 (co-surfactant). The ISL-SMEDDS exhibited an acceptable narrow size distribution (44.78 ± 0.35 nm), negative zeta potential (- 10.67 ± 0.86 mV), and high encapsulation efficiency (98.17 ± 0.24%). The in vitro release study indicated that the release rates of the formulation were obviously higher in different release media (HCl, pH 1.2; PBS, pH 6.8; double-distilled water, pH 7.0) compared with the ISL solution. The oral bioavailability of the ISL-SMEDDS was enhanced by 4.71 times in comparison with the free ISL solution. More importantly, ISL-SMEDDS significantly reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in the model rats. Collectively, the prepared ISL-SMEDDS proved to be potential carriers for enhancing the solubility and oral bioavailability of ISL, as well as ameliorating its anti-hyperuricemic effect.


Assuntos
Chalconas/administração & dosagem , Chalconas/sangue , Sistemas de Liberação de Medicamentos/métodos , Hiperuricemia/sangue , Hiperuricemia/tratamento farmacológico , Administração Oral , Animais , Disponibilidade Biológica , Emulsões , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/sangue , Masculino , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/metabolismo , Ratos , Ratos Sprague-Dawley , Solubilidade , Tensoativos/administração & dosagem , Tensoativos/metabolismo
9.
J Pharm Pharmacol ; 71(8): 1324-1338, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31168820

RESUMO

OBJECTIVES: Cuminaldehyde self-emulsified nanoemulsion (CuA-SEN) was prepared and optimised to improve its oral bioavailability and antihepatotoxicity. METHODS: Cuminaldehyde self-emulsified nanoemulsion was developed through the self-nanoemulsification method using Box-Behnken Design (BBD) tool while appropriate physicochemical indices were evaluated. The optimised CuA-SEN was characterised via droplet size (DS), morphology, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, in-vitro release, and pharmacokinetic studies while its antihepatotoxicity was evaluated. KEY FINDINGS: Cuminaldehyde self-emulsified nanoemulsion with acceptable characteristics (mean DS-48.83 ± 1.06 nm; PDI-0.232 ± 0.140; ZP-29.92 ± 1.66 mV; EE-91.51 ± 0.44%; and drug-loading capacity (DL)-9.77 ± 0.75%) was formulated. In-vitro drug release of CuA-SEN significantly increased with an oral relative bioavailability of 171.02%. Oral administration of CuA-SEN to CCl4 -induced hepatotoxicity mice markedly increased the levels of superoxide dismutase, glutathione and catalase in serum. Also, CuA-SEN reduced the levels of tumour necrosis factor-alpha and interleukin-6 in both serum and liver tissues while aspartate aminotransferase, alanine aminotransferase and malonaldehyde levels were significantly decreased. CONCLUSIONS: These findings showed that the improved bioavailability of cuminaldehyde via SEN provided an effective approach for enhancing antioxidation, anti-inflammation and antihepatotoxicity of the drug.


Assuntos
Benzaldeídos/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Emulsões/farmacologia , Nanoestruturas/administração & dosagem , Animais , Benzaldeídos/sangue , Benzaldeídos/farmacocinética , Disponibilidade Biológica , Tetracloreto de Carbono/efeitos adversos , Catalase/sangue , /farmacocinética , Liberação Controlada de Fármacos/efeitos dos fármacos , Emulsões/farmacocinética , Glutationa/sangue , Masculino , Camundongos , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/sangue
10.
Food Chem Toxicol ; 131: 110531, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31136780

RESUMO

1-O-(4-hydroxymethylphenyl)-α-L-rhamnopyranoside (MPG) is a phenolic glycoside that exists in Moringa oleifera seeds with various health benefits, whereas its hepatoprotective effect is lacking clarification. Herein, MPG was isolated from Moringa oleifera seeds, and its hepatoprotection against CCl4-induced hepatotoxicity in L02 cells and ICR mice was investigated. Toxicity studies showed that MPG did not induce significant changes in organ coefficients and histological analysis, as well as exhibited no cytotoxicity. In vitro studies indicated that MPG substantially increased cell viability and intracellular SOD activities, and significantly inhibited LDH leakage in CCl4-treated cells. In vivo studies demonstrated that MPG significantly alleviated CCl4-induced hepatotoxicity in mice, as indicated by diagnostic indicators of hepatic injury, as well as the histopathological analysis. Moreover, MPG reduced the lipid peroxidation levels and regulated the inflammatory cytokines. Notably, MPG substantially suppressed the significant elevation of ROS production in hepatocytes of mice intoxicated with CCl4. Moreover, TUNEL assay demonstrated that MPG obviously inhibited hepatic apoptosis induced by CCl4. Altogether, these results suggested that MPG has excellent liver-protecting effects against hepatocytotoxicity induced by CCl4 in mice and L02 cells, which can be further developed as a valuable functional food additive or drug for the treatment of hepatic injury.


Assuntos
Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glicosídeos/farmacologia , Moringa oleifera/química , Sementes/química , Administração Oral , Animais , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Antioxidantes/toxicidade , Tetracloreto de Carbono/toxicidade , Linhagem Celular , Citocinas/metabolismo , Feminino , Glicosídeos/administração & dosagem , Glicosídeos/isolamento & purificação , Glicosídeos/toxicidade , Fígado/patologia , Masculino , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos
11.
J Microencapsul ; 36(3): 278-290, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31117852

RESUMO

This study was designed to investigate the bioavailability and targeting of myricetrin-loaded ternary micelles modified with and without TPGS. The particle diameters of myricetrin-loaded micelles and myricetrin-loaded-TPGS micelle were 30.93 ± 1.34 nm and 26.42 ± 0.89 nm, respectively, while their respective encapsulation efficiencies (m/m, %) were 83.3 ± 1.08 and 93.8 ± 1.18. The release rate of myricetrin in the micellar system clearly exceeded the free myricetrin in the three media (pH 6.8 phosphate buffer, pH 1.2 HCl solution and double distilled water). In vivo studies displayed that the bioavailability of myricetrin mixed micelles was remarkably improved than the free drug after oral administration. Moreover, the results of tissue distribution showed that myricetrin-loaded-TPGS micelles accumulated well in the liver tissue. Based on these results, it was speculated that myricetrin-loaded-TPGS micelles might act as a promising carrier for liver targeting with improved hepatic concentration of myricetrin compared with the myricetrin-loaded micelles.


Assuntos
Antioxidantes/administração & dosagem , Portadores de Fármacos/química , Flavonoides/administração & dosagem , Micelas , Vitamina E/química , Animais , Antioxidantes/farmacocinética , Disponibilidade Biológica , Flavonoides/farmacocinética , Masculino , Ratos Sprague-Dawley , Distribuição Tecidual
12.
Drug Dev Ind Pharm ; 45(8): 1265-1276, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30990749

RESUMO

The prevalence of hyperuricemia is relatively high worldwide, and a great number of patients are suffering from its complications. 6-shogaol, an alkylphenol compound purified from the root of ginger (Zingiber officinale Roscoe), has been proved to possess diverse pharmacological activities. However, its poor aqueous solubility usually leads to low bioavailability, and further clinical applications will be greatly discounted. The current study aimed to formulate a 6-shogaol-loaded-Self Microemulsifying Drug Delivery System (SMEDDS) to amend low aqueous solubility and bioavailability orally, as well as, potentiate the hyperuricemic activity of the 6-shogaol. SMEDDS was developed with central composite design established on a two system components viz., 18.62% W/W ethyl oleate (oil phase) and ratio of tween 80 (surfactant) to PEG 400 (co-surfactant) (1.73:1, W/W). Based on quadratic model, the navigation of the design space could generate spherically-shaped and homogenous droplets with respective mean particle diameter, polydispersity and of 20.00 ± 0.26 nm and 0.18 ± 0.02. The 6-shogaol-SMEDDS showed significant elevation of cumulative release compared with the free 6-shogaol and more importantly a 571.18% increment in the relative oral bioavailability of the drug. The predominant accumulation of 6-shogaol-SMEDDS in the liver suggested hepatic-targeting potentiality of the drug. Oral administration of 6-shogaol-SMEDDS in hyperuricemic rats also significantly decreased uric acid level and xanthine oxidase activity. Histological studies confirmed formulation groups indeed could provide better protection of kidney than free drug groups. Collectively, these findings indicated that the SMEDDS hold much promise in enhancing the oral delivery and therapeutic efficacy of 6-shogaol.


Assuntos
Catecóis/administração & dosagem , Catecóis/química , Emulsões/administração & dosagem , Emulsões/química , Hiperuricemia/tratamento farmacológico , Administração Oral , Animais , Disponibilidade Biológica , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Masculino , Camundongos , Tamanho da Partícula , Polietilenoglicóis/química , Ratos , Ratos Sprague-Dawley , Solubilidade/efeitos dos fármacos , Tensoativos/química
13.
Pharmaceutics ; 11(3)2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30845761

RESUMO

:6-shogaol is a promising anti-cancer and anti-inflammatory agent. However, the treatment effectiveness of 6-shogaol is limited by poor water solubility, poor oral absorption and rapid metabolism. Herein, 6-shogaol loaded in micelles (SMs) were designed to improve 6-shogaol's solubility and bioavailability. The micelles of a PEG derivative of linoleic acid (mPEG2k-LA) were prepared by the nanoprecipitation method with a particle size of 76.8 nm, and entrapment of 81.6 %. Intriguingly, SMs showed a slower release in phosphate buffer saline (PBS) (pH = 7.4) compared to free 6-shogaol while its oral bioavailability increased by 3.2⁻fold in vivo. More importantly, the in vitro cytotoxic effect in HepG2 cells of SMs was significantly higher than free 6-shogaol. Furthermore, SMs could significantly improve the tissue distribution of 6-shogaol, especially liver and brain. Finally, SMs showed a better hepatoprotective effect against carbon tetrachloride (CCl4)-induced hepatic injury in vivo than free 6-shogaol. These results suggest that the novel micelles could potentiate the activities of 6-shogaol in cancer treatment and hepatoprotection.

14.
Int J Pharm ; 563: 53-62, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30890449

RESUMO

Isoliquiritigenin (ISL) has a great variety of pharmacological effects especially liver cancer therapy, but its poor solubility, bioavailability and liver targeting have limited its clinical use. In order to solve the aforementioned shortcomings, the TPGS-modified proliposomes loaded with ISL (ISL-TPGS-PLP) was prepared in this study. ISL-TPGS-PLP was fabricated via thin-film dispersion method and was characterized by the appearance, particle size, zeta potential and morphology. HPLC was used to evaluate entrapment efficiency (EE), in vitro release and stability of ISL-TPGS-PLP single or combined while appropriate physicochemical parameters were measured with DLS. Meanwhile, the pharmacokinetics and tissue distribution were also studied after oral administration. The results demonstrated that ISL-TPGS-PLP had a mean size of 23.8 ±â€¯0.9 nm, high EE of 97.33 ±â€¯0.40%. More importantly, nearly 90% ISL was released from ISL-TPGS-PLP within 24 h while only 50% was released from ISL suspension. In the pharmacokinetics study, the area under the curve (AUC0-24h) of ISL-TPGS-PLP was 1.53 times higher than that of ISL suspension. The Tissue distribution study showed that the ISL released from ISL-TPGS-PLP was higher in the liver than the free ISL suspension. Altogether, ISL-TPGS-PLP could ameliorate the ISL solubility, bioavailability and liver targeting ability, suggesting that ISL-TPGS-PLP could serve as a promising nanocarrier for liver cancer therapy.


Assuntos
Chalconas , Vitamina E , Administração Oral , Animais , Chalconas/administração & dosagem , Chalconas/química , Chalconas/farmacocinética , Composição de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Lipossomos , Fígado/metabolismo , Camundongos Endogâmicos ICR , Tamanho da Partícula , Ratos Sprague-Dawley , Solubilidade , Distribuição Tecidual , Vitamina E/administração & dosagem , Vitamina E/química , Vitamina E/farmacocinética
15.
AAPS PharmSciTech ; 20(4): 153, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30915610

RESUMO

The current investigation aimed at formulating self-microemulsifying drug delivery system (SMEDDS) to ameliorate oral bioavailability of a hydrophobic functional ingredient, limonene. Solubility test, compatibility test, and pseudo-ternary phase diagrams (PTPD) were adopted to screen the optimal compositions of limonene-SMEDDS (L-SMEDDS). The characteristics of this system assessed in vitro, mainly included determination of particle size distribution, observation of morphology via transmission electron microscopy (TEM), testing of drug release in different dissolution media, and evaluation of stability. The oral bioavailability study in vivo of the formulated limonene was performed in rats with the free limonene as the reference. Compared with the free limonene, the distribution study of L-SMEDDS was conducted in Kunming mice after oral administration. The optimized SMEDDS (ethyl oleate, 14.2%; Cremophor EL, 28.6%; isopropanol, 28.6%; and loaded limonene, 28.6%) under the TEM (about 100 nm) was spherical with no significant variations in size/appearance for 30 days at 4, 25, and 60°C. In comparison with free limonene, higher than 89.0% of limonene was released from SMEDDS within 10 min in different dissolution media. An in vivo study showed a 3.71-fold improved oral bioavailability of the formulated limonene compared to the free limonene. The tissue distribution results showed that limonene predominantly accumulated in the various tissues for the L-SMEDDS compared with the free limonene. Hence, L-SMEDDS could remarkably improve the concentration of limonene in the various organs. These findings hinted that the oral bioavailability of limonene could be improved via an effectual delivery system like SMEDDS.


Assuntos
Sistemas de Liberação de Medicamentos , Limoneno/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Liberação Controlada de Fármacos , Emulsões , Limoneno/química , Limoneno/farmacocinética , Masculino , Camundongos , Ratos , Ratos Sprague-Dawley , Solubilidade
16.
AAPS PharmSciTech ; 20(3): 98, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30719694

RESUMO

In this study, syringic acid-loaded TPGS liposome (SA-TPGS-Ls) was successfully prepared to improve oral bioavailability of syringic acid (SA). SA is a natural and notable antioxidant activity compound with its limited bioavailability ascribable to its poor aqueous solubility and fast elimination. Recently, TPGS has become a perfect molecular biomaterial in developing several carrier systems with sustained, controlled, and targeted the drug delivery. SA-TPGS-Ls was prepared via thin-film dispersion method and characterized in terms of particle size, stability, morphology, and encapsulation efficiency (EE). The results showed that SA-TPGS-Ls had regular spherical-shaped nanoparticles with EE of 96.48 ± 0.76%. The pharmacokinetic studies demonstrated a delayed MRT and prolonged t1/2, while relative oral bioavailability increased by 2.8 times. Tissue distribution showed that SA-TPGS-Ls maintained liver drug concentration while delayed elimination was also observed in the kidney. In CCl4-induced hepatotoxicity study, the activities of hepatic T-AOC, GSH-Px, CAT, GSH, and SOD were greatly elevated, while serum biological markers ALT, AST, and AKP were reduced after treatment of mice with SA-TPGS-Ls. Histopathological studies confirmed that SA-TPGS-Ls could remarkably improve the status of hepatic tissues. Collectively, SA-TPGS-Ls significantly improved the drug encapsulation efficiency, stability coupled with bioavailability of SA, hence increasing in vivo antioxidant activity of the drug.


Assuntos
Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Ácido Gálico/análogos & derivados , Lipossomos , Vitamina E/administração & dosagem , Vitamina E/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Intoxicação por Tetracloreto de Carbono/enzimologia , Intoxicação por Tetracloreto de Carbono/metabolismo , Ácido Gálico/administração & dosagem , Ácido Gálico/farmacocinética , Meia-Vida , Masculino , Camundongos , Nanopartículas , Tamanho da Partícula , Polietilenoglicóis , Ratos , Ratos Sprague-Dawley , Solubilidade , Distribuição Tecidual
17.
Drug Dev Ind Pharm ; 45(8): 1224-1232, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30681382

RESUMO

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.


Assuntos
Chalconas/química , Chalconas/farmacocinética , Polietilenos/química , Polímeros/química , Polipropilenos/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Disponibilidade Biológica , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Masculino , Micelas , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Solubilidade/efeitos dos fármacos
18.
Int J Pharm ; 555: 270-279, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30471374

RESUMO

The anti-tumor efficacy of curcumin can be markedly improved by nano-drug self-delivery systems with high drug loading capacity and smart stimulus-triggered drug release in tumor cells. Herein, a type of novel, glutathione (GSH)-responsive, PEGylated prodrug nano-micelles (PPNMs) was prepared by self-assembly of curcumin-s-s-vitamin E/mPEG2k-DSPE mixture. The PPNMs (entrapment efficiency: 96.7%) was acceptably stable in water with a mean particle size of 29.84 nm. Compared with curcumin-loaded mPEG2k-DSPE nano-micelles (CUR-NMs), PPNMs showed a higher drug loading (1.68% vs 27.3%) and remarkably improved the chemical stability of curcumin in phosphate buffer saline (PBS) (pH = 7.4), 10% FBS culture medium, and rat plasma. In vitro release study showed that PPNMs could redox responsively control the release of curcumin from the prodrug. Moreover, PPNMs showed a cytotoxicity in HepG2 cells similar to that of the free curcumin; however, when the HepG2 cells were pretreated with 1 mM GSH, PPNMs displayed a markedly enhanced cytotoxicity and cellular uptake than the free curcumin. After intravenous injection, PPNMs showed an increased half-life in blood circulation (10.6-fold) and bioavailability (107-fold) compared with the free curcumin injection. Altogether, the prodrug nano-micelles represent a promising preparation for sustained and controlled delivery of curcumin with enhanced antitumor activity.


Assuntos
Antineoplásicos/administração & dosagem , Curcumina/administração & dosagem , Sistemas de Liberação de Medicamentos , Nanopartículas , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Disponibilidade Biológica , Curcumina/farmacocinética , Curcumina/farmacologia , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Glutationa/metabolismo , Células Hep G2 , Humanos , Masculino , Micelas , Oxirredução , Tamanho da Partícula , Polietilenoglicóis/química , Pró-Fármacos , Ratos , Ratos Sprague-Dawley
19.
Drug Dev Res ; 80(2): 230-245, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30414214

RESUMO

Punicic acid of pomegranate oil (PAP) has gained heightened interest due to several health benefits, such as anticarcinogenic, antidiabetic, and antiatherosclerotic properties. However, these bioactivities have been hampered by chemical instability, poor water solubility, rapid metabolism, and low bioavailability of PAP. Therefore, this study was aimed at optimizing the liposomal formulation of Triacylglycerol-bound punicic acid with its regioisomers (TPAR) for improved oral bioavailability and increased hepatoprotection through antioxidation and anti-inflammation. Herein, the optimized TPAR nanoliposome (TPAR-NL) was developed using thin-film dispersion method and subsequently characterized with appropriate indices. The optimized TPAR-NL produced fairly stable spherical nanoparticles (˂ 200 nm) with encapsulation efficiency (%EE) of 85.77%, as well as enhanced in vitro release and improved oral bioavailability. The TPAR-NL exhibited profound antihepatotoxic effect in mice pretreated with carbon tetrachloride (CCl4 ) via reduction of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels compared with free TPAR. The TPAR-loaded liposome also significantly reduced oxidative stress by increasing superoxide dismutase and glutathione levels while lowering malonaldehyde concentration compared with the free TPAR. The TPAR-LNF further exhibited remarkable anti-inflammatory activity compared with the free drug via inhibition of interleukin-6 and tumor necrosis factor-alpha generation. Thus, the developed nanoliposomes potentiated the antihepatotoxic activity of TPAR via antioxidation and anti-inflammation.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Ácidos Linolênicos/administração & dosagem , Nanopartículas/administração & dosagem , Triglicerídeos/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Antioxidantes/química , Antioxidantes/farmacocinética , Disponibilidade Biológica , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/patologia , Liberação Controlada de Fármacos , Ácidos Linolênicos/química , Ácidos Linolênicos/farmacocinética , Lipossomos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos Endogâmicos ICR , Nanopartículas/química , Ratos Sprague-Dawley , Triglicerídeos/química , Triglicerídeos/farmacocinética
20.
Int J Biol Macromol ; 123: 801-809, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30445085

RESUMO

In this present study, we investigated the anti-hyperuricemic and anti-gouty arthritis effect of a puried water-soluble polysaccharide (LJP-1) obtained from Lonicera japonica. A series of characterization of the purified polysaccharide were carried out in this paper. Monosaccharide analysis showed that LJP-1 composed of glucuronic acid, glucose, galactose, arabinose, and xylose at the ratio of 2.43:1:2.09:1.95:1.96, respectively. The estimated molecular weight of LJP-1 was 17.5 kDa. LJP-1 belonged to pyranose and possessed α- and ß -glycosidic configurations. Congo red test showed that LJP-1 had a spatial triple helix structure. In pharmacodynamic experiments, the anti-hyperuricemic activity of LJP-1 was studied using hyperuricemic SD rat model induced via potassium oxonate and hypoxanthine. The result showed that LJP-1 could obviously decrease the serum uric acid level and suppress xanthine oxidase (XOD) activity. Moreover, in the gouty arthritis model established by sodium urate crystals, the degree of swelling of the ankle joint, IL-1ß, IL-6, TNF-α and COX-2-related inflammatory factors levels in murine serum all declined. Taken together, these results demonstrated that LJP-1 has anti-gouty arthritis effect. Therefore, LJP-1 could serve as a promising candidate for developing novel natural anti-gouty agent.


Assuntos
Artrite Gotosa/tratamento farmacológico , Hiperuricemia/tratamento farmacológico , Lonicera/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Animais , Modelos Animais de Doenças , Inflamação/patologia , Espectroscopia de Ressonância Magnética , Masculino , Peso Molecular , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA