Biomedical subjects

S S Feng

Publications and source records attributed to S S Feng.

12 recordsLinked to original sources

PubMed2003

A novel controlled release formulation for the anticancer drug paclitaxel (Taxol): PLGA nanoparticles containing vitamin E TPGS.

Paclitaxel (Taxol) is one of the best antineoplastic drugs found from nature in the past decades. Like many other anticancer drugs, there are difficulties in its clinical administration due to its poor solubility. Therefore an adjuvant called Cremophor EL has to be employed, but this has been found to cause serious side-effects. However, nanoparticles of biodegradable polymers can provide an ideal solution to the adjuvant problem and realise a controlled and targeted delivery of the drug with better efficacy and fewer side-effects. The present research proposes a novel formulation for fabrication of nanoparticles of biodegradable polymers containing d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) to replace the current method of clinical administration and, with further modification, to provide an innovative solution for oral chemotherapy. In the modified solvent extraction/evaporation technique employed in this research, the emulsifier/stabiliser/additive and the matrix material can play a key role in determining the morphological, physicochemical and pharmaceutical properties of the produced nanoparticles. We found that vitamin E TPGS could be a novel surfactant as well as a matrix material when blended with other biodegradable polymers. The nanoparticles composed of various formulations and manufactured under various conditions were characterised by laser light scattering (LLS) for size and size distribution, scanning electron microscopy (SEM) and atomic force microscopy (AFM) for morphological properties, X-ray photoelectron spectroscopy (XPS) for surface chemistry and differential scanning calorimetry (DSC) for thermogram properties. The drug encapsulation efficiency (EE) and the drug release kinetics under in vitro conditions were measured by high performance liquid chromatography (HPLC). It was concluded that vitamin E TPGS has great advantages for the manufacture of polymeric nanoparticles for controlled release of paclitaxel and other anti-cancer drugs. Nanoparticles of nanometer size with narrow distribution can be obtained. A drug encapsulation efficiency as high as 100% can be achieved and the release kinetics can be controlled.

Antineoplastic Agents, Phytogenic↗

PubMed2002

Vitamin E TPGS used as emulsifier in the solvent evaporation/extraction technique for fabrication of polymeric nanospheres for controlled release of paclitaxel (Taxol).

The D-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) was applied in the present investigation as surfactant stabiliser to fabricate paclitaxel-loaded PLGA nanospheres in the solvent evaporation/extraction technique with successful achievement. Laser light scattering system (LLS), scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) were employed to characterise the nanopsheres fabricated in various recipes under various preparation conditions for size and size distribution, surface morphology, thermogram property and surface chemistry. Encapsulation efficiency and in vitro release was measured by the high-performance liquid chromatography (HPLC). The outcomes were discussed with respect to the development of polymeric nanospheres delivery system of the anticancer drug, paclitaxel (Taxol((R))). The produced nanospheres were found in fine spherical shape with smooth surfaces and without aggregation or adhesion. There was no significant difference in morphology between the vitamin E TPGS emulsified and PVA emulsified PLGA nanospheres. However, it was found that, in comparison with the traditional chemical emulsifier PVA, the TPGS could significantly improve the encapsulation efficiency of the drug in the PLGA nanospheres, which could be as high as 100%. The size of the vitamin E TPGS emulsified nanospheres ranged from 300 to 800 nm and the size distribution was narrow with polydispersity of 0.005-0.045. XPS investigation demonstrated that there were residual surfactant molecules remained on the surface although the TPGS could be washed out relatively thoroughly in the process of nanospheres formation. This finding was also confirmed by FTIR-PAS investigation of the nanospheres. The in vitro release indicated that the release property of paclitaxel from the nanospheres strongly depends on the emulsifier type employed in the fabrication. Our research shows that vitamin E TPGS could be an ideal and effective emulsifier.

Antineoplastic Agents, Phytogenic↗

PubMed2001

Fabrication, characterization and in vitro release of paclitaxel (Taxol) loaded poly (lactic-co-glycolic acid) microspheres prepared by spray drying technique with lipid/cholesterol emulsifiers.

Spray dry technique was applied to produce paclitaxel loaded microspheres of biodegradable poly (lactic-co-glycolic acid) (PLGA) as an alternative delivery system. Various emulsifiers such as L-alpha-dipalmitoyl-phosphatidylcholine (DPPC), cholesterol, polyvinyl alcohol (PVA), gelatin were incorporated in order to achieve high encapsulating efficiency of paclitaxel in the microspheres and desired properties for a sustained release. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) showed that the surface of the microspheres with high ratio of lipid was spherical and smooth. Those made with other emulsifiers had rougher surface with pores. Incorporation of lipid, cholesterol or gelatin can significantly increase the drug content in the microspheres. The differential scanning calorimetry (DSC) result indicated that the paclitaxel trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. The zeta potential of the microspheres was negative in general and was strongly influenced by the type of the emulsifiers used in fabrication. The system formulated with cholesterol was most stable. The release profiles of various formulations with PVA, gelatin as well as low ratio of DPPC showed almost zero-order release kinetics in the first 3 weeks after an initial burst less than 5% in the first day. The release rate then gradually decreased. The microspheres fabricated with high ratio of DPPC exhibited large initial burst. When cholesterol was combined together with DPPC as an emulsifier, the release became faster.

Antineoplastic Agents, Phytogenic↗

PubMed2001

Halofantrine-phospholipid interactions: monolayer studies.

The antimalarial agent halofantrine penetrates dipalmitolylphosphatidylcholine (DPPC) monolayers resulting in an increase in surface pressure and an expansion in area occupied by the lipid components of the monolayer. This phenomenon is observed at concentrations (0.05-0.2 microm) of halofantrine that have no surface activity. Penetration increases with drug concentration and is greatest at low initial surface pressures of the monolayer. A critical surface pressure of the DPPC monolayer has been determined from constant area and constant pressure conditions. The magnitude of these values support the hypothesis that halofantrine readily penetrates the DPPC monolayers. The presence of cholesterol in the DPPC monolayer hampers penetration and a lower critical surface pressure is obtained under such conditions. Even then, a slower rate of penetration is observed only in monolayers maintained at high initial surface pressures (10, 15 mN/m), corresponding to the liquid condensed phase of the monolayer, and not at low surface pressures (2.5, 5.0 mN/m). These results help to give a better understanding of the dynamics of the halofantrine-phospholipid interaction as well as the pharmacodynamic character of the drug.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2000

Identification of novel regions of allelic loss from a genomewide scan of esophageal squamous-cell carcinoma in a high-risk Chinese population.

Esophageal cancer is one of the most common fatal cancers worldwide. Deletions of genomic regions are thought to be important in esophageal carcinogenesis. We conducted a genomewide scan for regions of allelic loss using microdissected DNA from 11 esophageal squamous-cell carcinoma patients with a family history of upper gastrointestinal tract cancer from a high-risk region in north central China. Allelic patterns of 366 fluorescently labeled microsatellite markers distributed at 10-cM intervals over the 22 autosomal chromosomes were examined. We identified 14 regions with very high frequency (>/= 75%) loss of heterozygosity (LOH), including broad regions encompassing whole chromosome arms (on 3p, 5q, 9p, 9q, and 13q), regions of intermediate size (on 2q, 4p, 11p, and 15q), and more discrete regions identified by very high frequency LOH for a single marker (on 4q, 6q, 8p, 14q, and 17p). Among these 14 regions were 7 not previously described in esophageal squamous-cell carcinoma as having very high frequency LOH (on 2q, 4p, 4q, 6q, 8p, 14q, and 15q). The very high frequency LOH regions identified here may point to major susceptibility genes, including potential tumor suppressor genes and inherited gene loci, which will assist in understanding the molecular events involved in esophageal carcinogenesis and may help in the development of markers for genetic susceptibility testing and screening for the early detection of this cancer. Genes Chromosomes Cancer 27:217-228, 2000. Published 2000 Wiley-Liss, Inc.

Adult↗

PubMed2000

Study of synthesis and cardiovascular activity of some furoxan derivatives as potential NO-donors.

A series of hybrid molecules incorporating the furoxan and nicorandil moieties were designed as potential NO donors with cardiovascular and cerebrovascular activities. Thirty-six target molecules were successfully synthesized by conventional methods and characterized by infrared spectroscopy, 1H-NMR spectroscopy and high resolution mass spectra. The compounds were tested for their effects on KCl-induced contraction of rabbit thoracic aorta whose endothelium was denuded. Eight compounds were found to reduce KCl-induced contraction by more than 30% at 10 microM. All except one of these compounds are characterized by the presence of electron withdrawing groups in the phenyl ring attached via an amide or ester linkage to the furoxan moiety. The nature of the terminal carbonyl linkage (ester or amide) and the length or type of the alkyl chain bridging the two carbonyl functions have little effect on the activity. One of the active compounds, N-(4-methoxy-benzoyl)-N'-[3-methylfuroxanyl-4-carbonyl)piperazine (17i) was tested for hypotensive effects on anaesthesized rats at 1.5 mg/kg, and found to demonstrate a gradual and sustained hypotensive effect. The results suggest that the furoxan-nicorandil derivatives are a useful lead in the design of NO-donor compounds for hypertension.

Animals↗

PubMed2000

Nanospheres of biodegradable polymers: a system for clinical administration of an anticancer drug paclitaxel (Taxol).

INTRODUCTION: Paclitaxel is a natural antineoplastic drug. It has been approved by the Food and Drug Administration (FDA) for the treatment of various cancers, especially ovarian and breast cancers with the best effect over other anticancer agents. Due to its high hydrophobicity however, an excipient such as Cremophor EL has to be used, which causes additional serious side effects. This study was intended to investigate the feasibility to apply nanospheres of biodegradable polymers as an alternative system to achieve best results with least side effects. MATERIALS AND METHODS: FDA-approved biodegradable polymers such as poly(D, L-lactic-co-glycolic acid) (PLGA) and poly(D, L-lactic acid) (PLA) were used to fabricate paclitaxel-loaded nanospheres by the solvent extraction/evaporation technique. The nanospheres fabricated in various conditions were characterised by laser light scattering for size and size distribution, scanning electron microscopy (SEM) and atomic force microscopy (AFM) for surface morphology, X-ray photoelectron spectroscopy (XPS) for the chemical structure of the surface. The drug encapsulation efficiency (EE) and the in vitro release kinetics were measured by HPLC. RESULTS: The products ranged from 300 nm to 700 nm with low polydispersity. The in vitro drug release can last more than 6 months at an approximately constant rate after an initial burst. The release kinetics can be fully controlled by the material used and the fabrication conditions. CONCLUSIONS: Nanospheres of biodegradable polymers can be an ideal carrier for pacitaxel to eliminate the side effects caused by the excipient currently used in clinical administration. The technique developed can also be applied to other anticancer drugs.

Antineoplastic Agents, Phytogenic↗

PubMed1995

Effects of chain unsaturation on the equation of state for lipid monolayers at the air-water interface.

An equation of state for lipid monolayers at the air-water interface is presented, which takes into account the effects of the conformation and the number and position of double bonds of the hydrocarbon chains. The total Hamiltonian of the monolayer is assumed to consist of three terms. Two of them are calculated exactly within the limitations of the formulation. These are the two-dimensional entropy of mixing of the lipid and water molecules at the surface and the conformational entropy of the chains using a model available from the literature. These two terms give rise to positive surface pressure. The third term, which includes all energies that are not amenable to calculation, was obtained as the difference between the sum of the two calculated terms and experimental data and is found to represent an approximately area-independent tension. The effects of chain unsaturation on the equation of state were modeled in the present theory in two ways; the chain bend caused by cis double bonds increases the minimal molecular area, and the double bond linkage on a chain decreases the degrees of freedom of the chain. Calculations revealed that the former is highly significant whereas the latter is negligible. The deduced equation of state reproduces experimental data with appropriate values for three parameters, which represent the collapse area, the overlap of adjacent chains, and the combined effects of the intra- and intermolecular interactions other than the surface mixing entropy and the chain conformational energy.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1990

The dynamics of shear disaggregation of red blood cells in a flow channel.

Red blood cell (RBC) rouleaux were formed in a flow channel in the presence of 2 g/dl dextran (molecular weight 76,000). The partial separation of RBC rouleau doublets adhering to the floor of the flow channel in response to small oscillatory shear stresses was observed experimentally. Theoretical analyses on displacement and drag force were performed to determine whether the motion of the cell involves membrane rotation (i.e., rolling) or sliding. From the experimental data and the results of theoretical analyses, it is concluded that, under the conditions of the experiments, the RBCs in a doublet separate from each other by rolling, rather than sliding of the sheared cell.

Biomechanical Phenomena↗

PubMed1990

[Clinicopathologic studies of 100 cases of lymph node metastasis in cardiac carcinoma].

The specimens of 100 cases of carcinoma of the gastric cardiac were studied after curative resection between 1985 and 1988. A total of 2213 lymph nodes were obtained, which were then divided into 23 group and 3 station in accordance with the Japanese staging system for esophageal and gastric carcinoma. Our data were as follow: (1) Eighty eight out of the hundred had lymph nodes metastasis, giving a metastatic rate of 88%: (2) 647 of 2213 lymph nodes were positive for metastasis. The degree of metastasis was 29.2%. The degree of metastasis of station 1,2,3 were 32%, 32.82%, and 14.65% respectively. That of group 1,2,3,4,7 and 110 were 42.5%, 32%, 36%, 11%, 39%, and 20.5% respectively. The lymph nodes of group 12, 14, 15, 16 and 17 were not involved; (3) The extent of lymph nodes metastasis of cardiac carcinoma were closely related the bulk of carcinoma, gross appearance, depth of infiltration and histological type (P less than 0.05). The authors consider that abdominal lymph node metastasis were of importance for cardiac carcinoma. The group 7 should be cleaned first. Lymph nodes dissection would be started from the level of inferior pulmonary vein and ended at the pylorus region.

Adenocarcinoma↗

PubMed1989

Velocity distribution on the membrane of a tank-treading red blood cell.

The kinematics of an area-conserving tank-treading disk-shaped red blood cell membrane is studied using the stream function method suggested by Secomb and Skalak (Q. Jl Mech. appl. Math. 35, Pt 2, 233-247, 1982). Two simple area-conserving velocity fields are superimposed to satisfy the continuity condition at the curved edges of the disk. A differential equation for the trajectory of any material point of the membrane is derived. The requirement of synchrony of the cycle for all membrane points leads to an integral equation which determines a magnitude function. An approximate solution is made possible by assuming small trajectory deflections.

Biomechanical Phenomena↗

PubMedDate not supplied

Release of paclitaxel from polylactide-co-glycolide (PLGA) microparticles and discs under irradiation.

Paclitaxel is a promising anti-cancer drug as well as a radiosensitizer for chemotherapy and radiotherapy applications. Because of the poor solubility of paclitaxel in water and most pharmaceutical reagents, it is usually formulated with an adjuvant called Cremophor EL, which causes severe side effects. This work develops new dosage forms of paclitaxel for controlled release application, which do not require the adjuvant and, thus, can avoid its associated side effects. Paclitaxel was encapsulated into the PLGA matrix with various additives such as polyethylene glycol (PEG), isopropyl myristate (IPM) and d-alpha tocopheryl polyethylene glycol (Vitamin E TPGS). These additives were used to enhance the release rate of paclitaxel from the polymer matrix. Spray-drying and an hydraulic press were used to prepare paclitaxel-PLGA microspheres and discs. The microspheres and discs were given different irradiation doses to investigate their effects on the surface morphology (characterized by SEM, AFM and XPS) and in vitro release properties. There seems to be a small effect of the ionizing radiation on various formulations. Although the irradiation did not cause observable changes on the morphology of the polymer matrix, the release rate can be enhanced by a few per cent. It was found that PEG has the highest enhancement effect for release rate among all the additives investigated in this study.

Antineoplastic Agents, Phytogenic↗