Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Drug Deliv ; 28(1): 2415-2426, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34763595

ABSTRACT

Koumine (KME) is an active alkaloid extracted from Gelsemium elegans, and its diverse bioactivities have been studied for decades. However, KME exhibits poor solubility and low oral bioavailability, which hampers its potential therapeutic exploitation. This work aimed to develop optimized inclusion complexes to improve the bioavailability of KME. The KME/hydroxypropyl-ß-cyclodextrin (KME/HP-ß-CD) inclusion complexes were prepared by the solvent evaporation method and later optimized using the Box-Behnken design. The optimal KME/HP-ß-CD was characterized by scanning electron microscopy, Fourier transforms infrared spectroscopy, differential scanning calorimetry, and nuclear magnetic resonance spectroscopy. The physicochemical characterization results revealed that the crystalline state of KME was transformed into an amorphous form, forming KME/HP-ß-CD inclusion complexes. Compared with KME, the solubility and in vitro release rate of KME/HP-ß-CD was significantly enhanced by 52.34- and 1.3-fold, respectively. Further research was performed to investigate the intestinal absorption characteristics and in vivo bioavailability in rats. The optimal KME/HP-ß-CD showed enhanced absorptive permeability and relative bioavailability increased more than two-fold compared to that of raw KME. These results indicate that the optimal KME/HP-ß-CD can be used as an effective drug carrier to improve the solubility, intestinal absorption, and bioavailability of KME.


Subject(s)
2-Hydroxypropyl-beta-cyclodextrin/chemistry , Drug Carriers/chemistry , Indole Alkaloids/administration & dosage , Indole Alkaloids/pharmacokinetics , Administration, Oral , Animals , Area Under Curve , Calorimetry, Differential Scanning , Cell Line, Tumor , Cell Survival , Chemistry, Pharmaceutical , Drug Liberation , Humans , Intestinal Absorption , Male , Microscopy, Electron, Scanning , Random Allocation , Rats , Rats, Sprague-Dawley , Solubility , Spectroscopy, Fourier Transform Infrared
2.
Mol Reprod Dev ; 85(1): 7-16, 2018 01.
Article in English | MEDLINE | ID: mdl-29149484

ABSTRACT

This study sought to identify sources of the reduced fertility of men with type 2 diabetes mellitus. Significant reductions in semen volume, sperm concentration, and total sperm count were observed in diabetic individuals, while transmission electron microscopy revealed that the structure of mitochondria in the tail of sperm from diabetic patients was damaged. Proteins potentially associated with these sperm defects were identified using proteomics. Isobaric tagging for relative and absolute quantitation labeling and high-performance liquid chromatography-tandem mass spectrometry allowed us to identify 357 proteins significantly differentially expressed in diabetic versus control semen (>1.2 or <0.83). According to gene ontology enrichment and pathway analyses, many of these differentially expressed proteins are associated with sperm function, including binding of sperm to the zona pellucida and proteasome function; of particular interest, half of these proteins were related to mitochondrial metabolism. Protein-interaction networks revealed that a decrease in Cystatin C and Dipeptidyl peptidase 4 in the mitochondria may be sources of the decreased motility of sperm from diabetic patients.


Subject(s)
Diabetes Mellitus, Type 2/pathology , Fertility/physiology , Infertility, Male/pathology , Mitochondria/metabolism , Semen Analysis , Sperm Motility/physiology , Adult , Apoptosis Inducing Factor/analysis , Biomarkers/analysis , Chromatography, High Pressure Liquid , Cystatin C/analysis , Diabetes Mellitus, Type 2/etiology , Dipeptidyl Peptidase 4/analysis , Humans , Infertility, Male/complications , Male , Middle Aged , Mitochondrial Proteins/analysis , Sperm Count , Spermatozoa/physiology , Tandem Mass Spectrometry
SELECTION OF CITATIONS
SEARCH DETAIL