Hydroxypropyl methylcellulose (HPMC) propels self-emulsifying drug delivery systems (SEDDS) to achieve the supersaturated state in gastrointestinal tract, which possesses important significance to enhance oral absorption for poorly water-soluble drugs. This study investigated capacities and mechanisms of HPMC with different viscosities (K4M, K15M and K100M) to inhibit drug precipitation of SEDDS in the simulated gastrointestinal tract environment in vitro. The results showed that HPMC inhibited drug precipitation during the dispersion of SEDDS under gastric conditions by inhibiting the formation of crystal nucleus and the growth of crystals. HPMC had evident effects on the rate of SEDDS lipolysis and benefited the distribution of drug molecules across into the aqueous phase and the decrease of drug sediment. The mechanisms were related to the formed network of HPMC and its viscosities and molecular weight. These results offered a reference for selecting appropriate type of HPMC as the precipitation inhibitor of supersaturatable SEDDS.
Caprylates ; chemistry ; Chemical Precipitation ; drug effects ; Crystallization ; Drug Delivery Systems ; methods ; Emulsifying Agents ; chemistry ; Emulsions ; Ethylene Glycols ; chemistry ; Glycerides ; chemistry ; Hypromellose Derivatives ; administration & dosage ; chemistry ; pharmacology ; Indomethacin ; administration & dosage ; chemistry ; Lipolysis ; drug effects ; Molecular Weight ; Polyethylene Glycols ; chemistry ; Viscosity

Total paeony glycoside (TPG) is extracted and purified from a traditional Chinese herbal medicine. It has many biological and pharmacological activities. However, there are few dosage forms of TPG in the market because of its low bioavailability. Self-microemulsifying drug delivery system (SMEDDS) is a vital tool in solving low bioavailability of poor absorption drugs. So the objective of this study is to develop a new TPG-SMEDDS for the oral delivery of poorly soluble TPG. Through the construction of pseudo-ternary phase diagrams, the optimum prescription was obtained, which consisted of 18.70% TPG, 16.27% ethyl oleate as oil, 43.34% Cremophor RH40 as surfactant and 21.73% Transcutol P as cosurfactant. The characterizations of TPG-SMEDDS including morphological characterization, droplet size, zeta-potential, emulsification time, and dissolution study of TPG-SMEDDS were evaluated. The results showed that TPG-SMEDDS is stable and its release rate is high in four different media (0.1 mol x L(-1) HCl, pH 6.8 PBS, pH 7.4 PBS, and water). The relative bioavailability of SMEDDS was dramatically enhanced in an average of 1.52-fold that of TPG-suspension. It is concluded that the bioavailability of TPG is enhanced greatly by SMEDDS.
Administration, Oral ; Animals ; Biological Availability ; Drug Delivery Systems ; Drug Stability ; Emulsions ; Ethylene Glycols ; chemistry ; Glycosides ; administration & dosage ; chemistry ; isolation & purification ; pharmacokinetics ; Oleic Acids ; chemistry ; Paeonia ; chemistry ; Particle Size ; Pharmaceutical Vehicles ; chemistry ; Plants, Medicinal ; chemistry ; Polyethylene Glycols ; chemistry ; Rats ; Solubility

OBJECTIVETo investigate the effects of labrasol, solutol HS 15 and transcutol P on the corneal permeability of mangiferin in vitro.

METHODThe effects of three penetration enhancers on the corneal permeability of mangiferin were investigated in vitro by using isolated rabbit corneas.

RESULTThe apparent Papp enhancements were increased 1.80, 3.27, 3.41 and 4.76-folds with Lab at 1.0%, 1.5%, 2.0% and 3.0% (P < 0.01), respectively. The apparent Papp increased 1.98 and 3.07-folds with Sol at 0.2% and 0.4% (P < 0.01), respectively, but reduced with 0.010%-0.03% Trans.

CONCLUSIONThe Papp value of mangiferin is significantly enhanced by 1.0%-3.0% Lab, 0.2% and 0.4% Sol, however the Papp value of mangiferin is reduced by 0.01%-0.03% Trans.

Animals ; Cornea ; drug effects ; metabolism ; Drug Carriers ; chemistry ; Ethylene Glycols ; chemistry ; Glycerides ; In Vitro Techniques ; Organic Chemicals ; chemistry ; Permeability ; Plant Extracts ; pharmacokinetics ; Polyethylene Glycols ; chemistry ; Rabbits ; Stearic Acids ; chemistry ; Xanthones ; pharmacokinetics

This study aimed to investigate the independent and interactive influences of apolipoprotein E (APOE) epsilon4 and beta-amyloid (Abeta) on multiple cognitive domains in a large group of cognitively normal (CN) individuals and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Participants were included if clinical and cognitive assessments, amyloid imaging, and APOE genotype were all available from the Alzheimer's Disease Neuroimaging Initiative database (CN = 324, MCI = 502, AD = 182). Individuals with one or two copies of epsilon4 were designated as APOE epsilon4 carriers (epsilon4+); individuals with no epsilon4 were designated as APOE epsilon4 non-carriers (epsilon4-). Based on mean florbetapir standard uptake value ratios, participants were classified as Abeta burden-positive (Abeta+) or Abeta burden-negative (Abeta-). In MCI, APOE epsilon4 effects were predominantly observed on frontal executive function, with epsilon4+ participants exhibiting poorer performances; Abeta positivity had no influence on this effect. Abeta effects were observed on global cognition, memory, and visuospatial ability, with Abeta+ participants exhibiting poorer performances. Measures of frontal executive function were not influenced by Abeta. Interactive effects of APOE epsilon4+ and Abeta were observed on global cognition and verbal recognition memory. Abeta, not APOE epsilon4+, influenced clinical severity and functional status. The influences of APOE epsilon4+ and Abeta on cognitive function were minimal in CN and AD. In conclusion, we provide further evidence of both independent and interactive influences of APOE epsilon4+ and Abeta on cognitive function in MCI, with APOE epsilon4+ and Abeta showing dissociable effects on executive and non-executive functions, respectively.
Aged ; Aged, 80 and over ; Alzheimer Disease/genetics/pathology ; Amyloid beta-Peptides/*metabolism ; Aniline Compounds/chemistry ; Apolipoprotein E4/*genetics ; Brain/radiography ; Cognition ; Databases, Factual ; Demography ; Ethylene Glycols/chemistry ; Female ; Genotype ; Humans ; Male ; Mild Cognitive Impairment/genetics/*pathology ; Positron-Emission Tomography

The aim of this study is to prepare self-microemulsifying drug delivery system (SMEDDS) of the mixture of paeonol (Pae) and borneol (Bor). Solubility test, ternary phase diagrams and simplex lattice method were employed to screen and optimize the formulation of the mixture of Pae and Bor-loaded SMEDDS. After formed into microemulsions, the particle diameter (PD) was determined and a TEM was employed to observe the microemulsions' morphology. The contents of Pae and Bor were determined by gas chromatography. As a result, while ethyl oleate (EO) as the oil phase, cremophor EL35 (EL35) as surfactant and Transcutol HP (HP) as cosurfactant, the range of the microemulsion on the ternary phase diagram was larger than other combinations. And at a ratio of 20:45:35, the microemulsions' PD was about 34 nm and the polydispersity index (PI) was about 0.2. There were 16% of Pae, 2% of Bor, 16% of EO, 37% of EL35 and 29% of HP in the prepared SMEDDS. The preparation process of the Pae and Bor-loaded SMEDDS based on Xingbi Fang is simple and feasible. This study provides a reference for the researches on the related traditional Chinese medicine and the related components.
Acetophenones ; administration & dosage ; toxicity ; Administration, Intranasal ; Animals ; Bornanes ; administration & dosage ; toxicity ; Bufonidae ; Cilia ; drug effects ; Drug Combinations ; Drug Delivery Systems ; methods ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Emulsions ; Ethylene Glycols ; chemistry ; Female ; Male ; Nasal Mucosa ; drug effects ; Oleic Acids ; chemistry ; Particle Size ; Polyethylene Glycols ; chemistry ; Solubility ; Surface-Active Agents ; chemistry

The aim of this paper is to compare the cytotoxicity and cellular uptake efficiency of three kinds of poly(b-benzyl-L-amino) block-poly(ethylene glycol) nanoparticles (PXA-PEG-NPs) using Calu-3 cells, and select one as a nasal drug delivery vector for curcumin (Cur). Poly(gamma-benzyl-L-glutamate) block-poly(ethylene glycol) nanoparticles (PBLG-PEG-NPs), poly(gamma-benzyl-L-lysine) block-poly(ethyleneglycol) nanoparticles (PZLL-PEG-NPs) and poly(gamma-benzyl-L-aspartate) block-poly(ethylene glycol) nanoparticles (PBLA-PEG-NPs) were prepared by emulsion-solvent evaporation method. MTT assays were used to evaluate the cytotoxicity of PXA-PEG-NPs against Calu-3 cells. The cellular uptake of nanoparticles was visualized by an inverted fluorescence microscope and quantified by a flow cytometer. The results indicated that even at high concentration of 2 mg x mL(-1) the three nanoparticles had no cytotoxicity on Calu-3 cells. Compared to the curcumin solution, the three curcumin-loaded PXA-PEG-NPs showed significantly higher cellular uptake efficiency on Calu-3 cells (at equal concentration of curcumin with 5 microg x mL(-1) Cur solution), PBLG-PEG-NPs group was the highest. The cellular uptake increased with incubation time, and has positive correlation with nanoparticle concentration. In brief, PXA-PEG-NPs are conducive to delivery Cur into cells, and PBLG-PEG-NPs might be provided as a good nasal drug delivery carrier.
Adenocarcinoma ; metabolism ; pathology ; Administration, Intranasal ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; metabolism ; Aspartic Acid ; chemistry ; toxicity ; Cell Line, Tumor ; Cell Survival ; drug effects ; Curcumin ; administration & dosage ; metabolism ; Drug Carriers ; Ethylene Glycol ; chemistry ; toxicity ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Lysine ; chemistry ; toxicity ; Nanoparticles ; Particle Size ; Polyethylene Glycols ; chemistry ; toxicity ; Polyglutamic Acid ; analogs & derivatives ; chemistry ; toxicity