Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
Colloids Surf B Biointerfaces ; 193: 111069, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32371286

ABSTRACT

Cajaninstilbene acid (CSA) exerts wide pharmacological activities, such as anti-inflammation, hypoglycaemic activity, analgesic effect and cognition improvement. However, it underwent severe phase II metabolism mediated by UDP-glucuronosyltransferase (UGT) in the gastrointestinal (GI) tract after oral administration, affecting its oral bioavailability. In the present study, we utilize UGT inhibitory excipient containing self-microemulsion (SME) delivery system to reduce the production of glucuronide metabolites and increase its oral bioavailability. The present results showed that although similar properties in physiochemical, cytotoxicity, cellular uptake, absorption and transport across rat everted gut sacs between SME-1 (inhibitory excipient containing SME) and SME-2 (control SME, without inhibitory excipient), an improved absolute bioavailability of 57.3 % was conferred by SME-1, significantly higher than the value of 35.4 % by SME-2 and 34.0 % by free CSA. Noticeably, the significantly lower AUC value of CSA glucuronide was determined in rats treated with SME-1 than those either treated with SME-2 or free CSA. Thus, the ability of SME-1 to enhance oral bioavailability of CSA is mainly attributed to the inhibition of phase II metabolism in the GI tract.


Subject(s)
Enzyme Inhibitors/pharmacology , Glucuronosyltransferase/antagonists & inhibitors , Salicylates/pharmacology , Stilbenes/pharmacology , Administration, Oral , Animals , Biological Availability , Emulsions/administration & dosage , Emulsions/pharmacology , Enzyme Inhibitors/administration & dosage , Glucuronosyltransferase/metabolism , Humans , Male , Rats , Rats, Wistar , Salicylates/administration & dosage , Stilbenes/administration & dosage , Tumor Cells, Cultured
2.
Int J Pharm ; 572: 118839, 2019 Dec 15.
Article in English | MEDLINE | ID: mdl-31715359

ABSTRACT

This study intended to investigate the in vivo pulmonary fate of intratracheally dosed nanosuspensions of fluticasone propionate (FP). Three FP suspensions, including a microsuspension and two nanosuspensions with different dissolution profiles, were prepared and they exhibited comparable aerodynamic performances after nebulization via a jet nebulizer. Following intratracheal administration to rats, the microsuspension underwent extensive mucociliary clearance, leading to a limited absorption time whereas the nanosuspensions decreased the mucociliary clearance and allowed dissolution rate-limiting and extended pulmonary absorption, resulting in prolonged pulmonary retention and long-acting anti-inflammatory efficacy in a lipopolysaccharide induced lung injury model. Delaying the FP dissolution of a nanosuspension by phospholipid coating increased AUC value in lung tissues to 1.72-fold of a conventional nanosuspension, but led to a decreased pharmacological efficacy. This study demonstrated that inhalable nanosuspensions were a feasible means for the sustained pulmonary delivery of FP and the local anti-inflammatory efficacy was highly dependent on the dissolution profiles.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Fluticasone/administration & dosage , Lung Injury/drug therapy , Nanoparticles , Administration, Inhalation , Animals , Anti-Inflammatory Agents/pharmacokinetics , Anti-Inflammatory Agents/pharmacology , Area Under Curve , Delayed-Action Preparations , Disease Models, Animal , Drug Liberation , Fluticasone/pharmacokinetics , Fluticasone/pharmacology , Lung/metabolism , Male , Mice , Mice, Inbred BALB C , Nebulizers and Vaporizers , Rats , Rats, Wistar , Suspensions , Tissue Distribution
3.
ACS Appl Mater Interfaces ; 11(6): 5821-5833, 2019 Feb 13.
Article in English | MEDLINE | ID: mdl-30645095

ABSTRACT

In this study, we established a long-term three-dimensional (3D) culture system by using integrin ligand modified alginate hydrogels to encapsulate and differentiate neural progenitor cells (NPCs) toward oligodendrocyte (OL) lineage cells. The porosity of the hydrogel was optimized by varying the alginate concentrations and then characterized by scanning electronic microscopy (SEM). The surface plasmon resonance (SPR) test was used to confirm the ligand-integrin interactions indicating adherence between the NPC surfaces and the hydrogels. Following encapsulation in the hydrogels, both mouse and human NPC sphere cultures could be maintained up to 90 days. Mouse NPC spheres were differentiated into viable neurons, astrocytes and mature OLs by day 60 in all groups whereas human NPC spheres were differentiated into neurons and later into GFAP positive astrocytes and O4 positive pre-OL within 90 days. The species difference in the timeline of OL development between mouse and human was reflected in this system. The ligand LXY30 interacting with the α3ß1 integrin receptor was more effective in promoting the differentiation of hNPCs to OL lineage cells compared with the ligand LXW64 interacting with the αvß3 integrin receptor, hyaluronic acid interacting with CD44 receptor or without any ligand. This study is the first to differentiate O4+ pre-OLs from hNPCs in a LXY30-α3ß1 (integrin-ligand) modified alginate 3D hydrogel culture. This 3D platform could serve as a valuable tool in disease modeling, drug discovery, and NPC transplantation.


Subject(s)
Alginates/chemistry , Cell Differentiation/drug effects , Hydrogels/chemistry , Integrin alpha3beta1/metabolism , Ligands , Animals , Cell Culture Techniques , Cell Survival/drug effects , Glial Fibrillary Acidic Protein/metabolism , Humans , Hydrogels/metabolism , Hydrogels/pharmacology , Integrin alpha3beta1/chemistry , Mice , Microscopy, Electron, Scanning , Neural Stem Cells/cytology , Neural Stem Cells/metabolism , Oligodendroglia/cytology , Oligodendroglia/metabolism , Spheroids, Cellular/cytology , Spheroids, Cellular/drug effects , Spheroids, Cellular/metabolism
4.
Eur J Pharm Sci ; 114: 303-309, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29292019

ABSTRACT

Self-microemulsifying (SME) drug delivery system has been developed to increase oral bioavailabilities, and inhibitory excipients are capable of improving oral bioavailability by inhibiting enzyme mediated intestinal metabolism. However, the potential of enzyme inhibitory excipients containing SME in boosting resveratrol bioavailability remains largely uninvestigated. In this study, we set out to prepare SME-1 with UGT inhibitory excipients (excipients without inhibitory activities named SME-2 as control) to increase the bioavailability of RES by inhibiting intestinal metabolism. Results demonstrated that similar physicochemical properties such as size, polydistribution index and in vitro release, cellular uptake and permeability in Caco-2 cells as well as in vivo lymphatic distribution between inhibitory SME-1 and non-inhibitory SME-2 were observed. In vivo study demonstrated that the molar ratios of RES-G/RES were 7.25±0.48 and 5.06±2.42 for free drug and SME-2, respectively, and the molar ratio decreased to 0.36±0.10 in SME-1 group. Pharmacokinetic study confirmed that the inhibitory excipients containing SME demonstrated potential in increasing bioavailability of RES from 6.5% for the free RES and 12.9% for SME-2 to 76.1% in SME-1 through modulating the glucuronidation by UGT inhibitory excipients.


Subject(s)
Excipients/metabolism , Glucuronosyltransferase/antagonists & inhibitors , Glucuronosyltransferase/metabolism , Stilbenes/metabolism , Administration, Oral , Animals , Biological Availability , Caco-2 Cells , Emulsions , Excipients/administration & dosage , Gastrointestinal Absorption/drug effects , Gastrointestinal Absorption/physiology , Humans , Male , Rats , Rats, Wistar , Resveratrol , Stilbenes/administration & dosage
SELECTION OF CITATIONS
SEARCH DETAIL
...