Liposomal formulations for enhanced lymphatic drug delivery

AbstractThe lymphatic system that extends throughout the whole body is one of useful targets for efficient drug delivery. The intestinal lymphatic drug delivery has been actively studied to date because administered drugs can avoid the first-pass metabolism in the liver, resulting in improvement of oral bioavailability. Drugs must be hydrophobic in order to be transported into the intestinal lymphatics because the lipid absorption mechanism in the intestine is involved in the lymphatic delivery. Therefore, various lipid-based drug carrier systems have been recently utilized to increase the transport of drug into the intestinal lymphatics. Lipidic molecules of the lipid-based drug delivery systems stimulate production of chylomicrons in the enterocytes, resulting in an increase in drug transport into lymphatic in the enterocytes. This review summarizes recently reported information on development of liposomal carriers for the intestinal lymphatic delivery and covers important determinants for successful lymphatic delivery

BAY 11-7082 Is a Broad-Spectrum Inhibitor with Anti-Inflammatory Activity against Multiple Targets

BAY 11-7082 (BAY) is an inhibitor of κB kinase (IKK) that has pharmacological activities that include anticancer, neuroprotective, and anti-inflammatory effects. In this study, BAY-pharmacological target pathways were further characterized to determine how this compound simultaneously suppresses various responses. Primary and cancerous (RAW264.7 cells) macrophages were activated by lipopolysaccharide, a ligand of toll-like receptor 4. As reported previously, BAY strongly suppressed the production of nitric oxide, prostaglandin E2, and tumor necrosis factor-α and reduced the translocation of p65, major subunit of nuclear factor-κB, and its upstream signaling events such as phosphorylation of IκBα, IKK, and Akt. In addition, BAY also suppressed the translocation and activation of activator protein-1, interferon regulatory factor-3, and signal transducer and activator of transcription-1 by inhibiting the phosphorylation or activation of extracellular signal-related kinase, p38, TANK-binding protein, and Janus kinase-2. These data strongly suggest that BAY is an inhibitor with multiple targets and could serve as a lead compound in developing strong anti-inflammatory drugs with multiple targets in inflammatory responses

Nanostructured, Self-Assembling Peptide K5 Blocks TNF-α and PGE2 Production by Suppression of the AP-1/p38 Pathway

Nanostructured, self-assembling peptides hold promise for a variety of regenerative medical applications such as 3D cell culture systems, accelerated wound healing, and nerve repair. The aim of this study was to determine whether the self-assembling peptide K5 can be applied as a carrier of anti-inflammatory drugs. First, we examined whether the K5 self-assembling peptide itself can modulate various cellular inflammatory responses. We found that peptide K5 significantly suppressed the release of tumor-necrosis-factor- (TNF-) α and prostaglandin E2 (PGE2) from RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Similarly, there was inhibition of cyclooxygenase- (COX-) 2 mRNA expression assessed by real-time PCR, indicating that the inhibition is at the transcriptional level. In agreement with this finding, peptide K5 suppressed the translocation of the transcription factors activator protein (AP-1) and c-Jun and inhibited upstream inflammatory effectors including mitogen activated protein kinase (MAPK), p38, and mitogen-activated protein kinase kinase 3/6 (MKK 3/6). Whether this peptide exerts its effects via a transmembrane or cytoplasmic receptor is not clear. However, our data strongly suggest that the nanostructured, self-assembling peptide K5 may possess significant anti-inflammatory activity via suppression of the p38/AP-1 pathway

MRI traceability of superparamagnetic iron oxide nanoparticle-embedded chitosan microspheres as an embolic material in rabbit uterus

PURPOSEWe aimed to compare polyvinyl alcohol (PVA) particles with calibrated superparamagnetic iron oxide (SPIO) nanoparticle-loaded chitosan microspheres in a rabbit model, specifically regarding the relative distribution of embolic agents within the uterus based on magnetic resonance imaging (MRI) and pathological evaluation.METHODSTwelve New Zealand white rabbits underwent uterine artery embolization using either standard PVA particles (45–150 µm or 350–500 µm) or calibrated SPIO-embedded chitosan microspheres (45–150 µm or 300–500 µm). MRI and histopathological findings were compared one week after embolization.RESULTSCalibrated SPIO-loaded chitosan microspheres 45–150 µm in size were detected on T2-weighted images. On histological analysis, calibrated SPIO-embedded chitosan microspheres were found in both myometrium and endometrium, whereas PVA particles were found only in the perimyometrium or extrauterine fat pads. A proportional relationship was noted between the calibrated SPIO-embedded chitosan microsphere size and the size of the occluded artery.CONCLUSIONCalibrated SPIO-embedded chitosan microspheres induced greater segmental arterial occlusion than PVA particles and showed great potential as a new embolic material. SPIO-embedded chitosan microspheres can be used to follow distribution of embolic particles through MRI studies

Effects of a Rubus coreanus Miquel supplement on plasma antioxidant capacity in healthy Korean men

Korean raspberry, Rubus coreanus Miquel (RCM), contains high concentrations of phenolic compounds, which prevent oxidative stress. To determine the effect of RCM on antioxidant capacity in humans, we assessed in vivo lipid oxidation and antioxidant enzyme activities from plasma in 15 healthy men. The subjects ingested 30 g of freeze-dried RCM daily for 4 weeks. Blood was taken at baseline and at the end of the study to determine blood lipid profiles, fasting plasma glucose, liver function, lipid peroxidation, and antioxidant enzyme activities. RCM supplementation had no effect on blood lipid or fasting plasma glucose concentrations but decreased alkaline phosphatase activity. RCM supplementation increased glutathione peroxidase activities (P < 0.05) but had no effect on lipid peroxidation. These results suggest that short-term RCM supplementation may offer health benefits by enhancing antioxidant capacity in a healthy population

Hydrotropic Hydrogels Prepared from Polyglycerol Dendrimers: Enhanced Solubilization and Release of Paclitaxel

Polyglycerol dendrimers (PGD) exhibit unique properties such as drug delivery, drug solubilization, bioimaging, and diagnostics. In this study, PGD hydrogels were prepared and evaluated as devices for controlled drug release with good solubilization properties. The PGD hydrogels were prepared by crosslinking using ethylene glycol diglycidylether (EGDGE). The concentrations of EGDGE and PGDs were varied. The hydrogels were swellable in ethanol for loading paclitaxel (PTX). The amount of PTX in the hydrogels increased with the swelling ratio, which is proportional to EGDGE/OH ratio, meaning that heterogeneous crosslinking of PGD made high dense region of PGD molecules in the matrix. The hydrogels remained transparent after loading PTX and standing in water for one day, indicating that PTX was dispersed in the hydrogels without any crystallization in water. The results of FTIR imaging of the PTX-loaded PGD hydrogels revealed good dispersion of PTX in the hydrogel matrix. Sixty percent of the loaded PTX was released in a sink condition within 90 min, suggesting that the solubilized PTX would be useful for controlled release without any precipitation. Polyglycerol dendrimer hydrogels are expected to be applicable for rapid release of poorly water-soluble drugs, e.g., for oral administration

Water quantitatively induces the mucoadhesion of liquid crystalline phases of glyceryl monooleate

The possible role of water in the mucoadhesion phenomenon exhibited by the liquid crystalline phases of glyceryl monooleate was investigated using an in-vitro tensile strength technique. The mucoadhesion of the liquid crystalline phases of glyceryl monooleate was found to occur following uptake of water. The mucoadhesive force of the cubic phase was consistent since it is not capable of taking up additional water. An increase in pre-load period greatly facilitated the mucoadhesion of glyceryl monooleate (0 % w/w initial water content), suggesting that the mucoadhesion is dependent upon the extent of the dehydration of the substrate. A good linear relationship between initial water content of the liquid crystalline phases and mucoadhesive force led to the conclusion that the mucoadhesive force increased with decreasing initial water concentration. Rheological properties of the liquid crystalline phases were also studied to allow a correlation between physical changes and mucoadhesion of the liquid crystalline phases, revealing that higher water concentrations in the liquid crystalline phases led to a more ordered structure that showed less mucoadhesion. The results of this study indicated that the mucoadhesive force of the liquid crystalline phases of glyceryl monooleate is determined by the capability to take up water from a water-rich environment. It may, therefore, be advantageous to use the lamellar phase as a buccal drug carrier as opposed to the relatively less mucoadhesive \ud cubic phase. \u