Biomedical subjects

Youxin Li

Publications and source records attributed to Youxin Li.

5 recordsLinked to original sources

PubMed2006

Pharmacokinetics of huperzine A in dogs following single intravenous and oral administrations.

The pharmacokinetics of huperzine A in dogs after single intravenous and oral administrations was investigated. Concentrations of huperzine A were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were calculated by non-compartmental methods. After single intravenous administration, the Cmax, T1/2, AUC0-t, AUC0-infinity, CL, Vd and Vss were 5.55 +/- 1.61 microg/L, 5.02 +/- 0.31 h, 16.04 +/- 5.24, 16.49 +/- 5.29 microgh/L, 0.66 +/- 0.19 L/h/kg, 4.76 +/- 1.46, and 3.93 +/- 1.54 L/kg, respectively. After single oral administration, the Cmax, Tmax, T1/2, AUC0-t, AUC0-infinity and oral bioavailability were 2.60 +/- 0.60 microg/L, 1.25 +/- 0.50 h, 5.71 +/- 2.25 h, 12.90 +/- 3.19, 13.78 +/- 3.24 microgh/L, and 94.4 +/- 36.5%, respectively. In conclusion, huperzine A had a rapid and nearly complete oral absorption and was extensively distributed into tissues after drug administration in dogs.

Administration, Oral↗

PubMed2003

In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis.

A comparative in vitro cytotoxicity study with different water-soluble, cationic macromolecules which have been described as gene delivery systems was performed. Cytotoxicity in L929 mouse fibroblasts was monitored using the MTT assay and the release of the cytosolic enzyme lactate dehydrogenase (LDH). Microscopic observations were carried out as indicators for cell viability. Furthermore, hemolysis of erythrocytes was quantified spectrophotometrically. To determine the nature of cell death induced by the polycations, the nuclear morphology after DAPI staining and the inhibition of the toxic effects by the caspase inhibitor zVAD.fmk were investigated. All assays yielded comparable results and allowed the following ranking of the polymers with regard to cytotoxicity: Poly(ethylenimine)=poly(L-lysine)>poly(diallyl-dimethyl-ammonium chloride)>diethylaminoethyl-dextran>poly(vinyl pyridinium bromide)>Starburst dendrimer>cationized albumin>native albumin. The magnitude of the cytotoxic effects of all polymers were found to be time- and concentration dependent. The molecular weight as well as the cationic charge density of the polycations were confirmed as key parameters for the interaction with the cell membranes and consequently, the cell damage. Evaluating the nature of cell death induced by poly(ethylenimine), we did not detect any indication for apoptosis suggesting that the polymer induced a necrotic cell reaction. Cell nuclei retained their size, chromatin was homogenously distributed and cell membranes lost their integrity very rapidly at an early stage. Furthermore, the broad spectrum caspase inhibitor zVAD.fmk did not inhibit poly(ethylenimine)-induced cell damage. Insights into the structure-toxicity relationship are necessary to optimize the cytotoxicity and biocompatibility of non-viral gene delivery systems.

Animals↗

PubMed2002

ABA-triblock copolymers from biodegradable polyester A-blocks and hydrophilic poly(ethylene oxide) B-blocks as a candidate for in situ forming hydrogel delivery systems for proteins.

Hydrogels are very attractive delivery systems for hydrophilic macromolecules such as proteins and DNA because they provide a protective environment and allow control of diffusion by adjusting cross-link densities. Physically cross-linked hydrogels generated by rapid swelling upon exposure to an aqueous environment can be obtained from ABA triblock copolymers containing hydrophobic polyester A-blocks and hydrophilic polyether B-blocks. They provide an attractive alternative to chemically cross-linked systems since they allow incorporation of macromolecular drug substances under mild process conditions. Moreover, they show controlled degradation behavior and excellent biocompatibility. In this review the synthesis and characterization of ABA triblock copolymers from polyester hard segments and poly(ethylene oxide) [PEO] soft segments as well as their biological and degradation properties will be discussed. Their use as biodegradable drug delivery devices in the form of implants, micro- and nanospheres has attracted considerable interest especially for proteins and may provide an alternative to poly(lactide-co-glycolide).

Animals↗

PubMed2002

Synthesis and characterization of poly(DL-lactide)-grafted gelatins as bioabsorbable amphiphilic polymers.

A series of poly(DL-lactide) grafted gelatins, as new bioabsorbable amphiphilic polymers useful in parenteral drug delivery systems and in tissue engineering, were synthesized by the ring opening polymerization of DL-lactide onto a fractionated gelatin with the molecular weight of 1.02 x 10(5). Using tin(II) bis(2-ethylhexanoate) as catalyst, the bulk copolymerization at 140 degrees C and solution copolymerization in dimethylsulfoxide (DMSO) at 80 degrees C were firstly performed in the presence of gelatin. The results showed that the solution copolymerization in DMSO could afford the expected copolymers but the bulk copolymerization would result in an insoluble crosslinked product. The number of grafting sites on gelatin chain could be adjusted by the partial trimethylsilylation of side hydroxy, amino and carboxylic groups in gelatin. The solution copolymerization of DL-lactide on the partially protected gelatin in DMSO was also successful in providing copolymers with different molecular weights. The synthesized copolymers were characterized on the basis of elemental analysis, IR, 1H-NMR and thermal analysis. The IR and 1H-NMR data of these produced copolymers suggested that polylactide branches could be grafted onto gelatin via the side groups such as hydroxyl and amino groups in the solution copolymerization as well as carboxylic groups in bulk copolymerization. The molecular weights of the copolymers could be calculated from the difference of nitrogen contents between a copolymer and free gelatin. The results indicated that molecular weight of the copolymers and those of polylactide branches were increased with the feeding ratio of DL-lactide to gelatin in the copolymerization. However, because of the steric hindrance of some grafting sites on gelatin and the transesterifications of the propagating polylactide branches on gelatin with possibly formed homo-polymeric polylactide chains, the finally formed polylactide branches on gelatin were not very large and the highest average molecular weight of a polylactide branch was not over 4500 in any solution copolymerizations. The results from the thermal analysis of some copolymers, including thermogravimetry and differential scanning calorimetry, showed that the absorbed water in the samples could be lost at a temperature range below 150 degrees C and melting point decreased with increase of polylactide branches in the poly(DL-lactide)-grafted gelatins.

Absorbable Implants↗

PubMedDate not supplied

Copolymers of ethylene imine and N-(2-hydroxyethyl)-ethylene imine as tools to study effects of polymer structure on physicochemical and biological properties of DNA complexes.

A series of five poly[(ethylene imine)-co-N-(2-hydroxyethyl-ethylene imine)] copolymers with similar molecular weights and different degrees of branching was established to study structure-function relationship with regard to physicochemical and biological properties as gene delivery systems. Copolymers were synthesized by acid-catalyzed ring-opening copolymerization of aziridine and N-(2-hydroxyethyl)-aziridine in aqueous solution and characterized by GPC-MALLS, (1)H- and (13)C NMR, IR, potentiometric titration, and ion exchange chromatography. Complexation of DNA was determined by agarose gel electrophoresis, and complex sizes were quantitated by PCS. Cytotoxicity of the copolymers in fibroblasts was assessed by MTT-assay, LDH-assay, and hemolysis. The transfection efficiency was determined using the reporter plasmid pGL3 in 3T3 mouse fibroblasts. The copolymers obtained by solution polymerization had relatively low molecular weights of about 2000 Da, and the degree of branching increased with increasing ethylene imine ratio. The pK(a) as well as the buffer capacity increased proportional to the number of primary and secondary amines. Higher branched polymers showed stronger complexation and condensation of DNA, formed smaller polymer/DNA complexes, and induced the expression of plasmids to a higher extent than less branched polymers. In vitro cytotoxic effects and the hemolysis of erythrocytes decreased with decreased branching. Our results indicate that the basicity and degree of protonation of the polymers depending on their amount of primary and secondary amines seem to be important factors both for their transfection efficiency and for their cytotoxicity in gene transfer.

3T3 Cells↗