Phase-equilibrium characteristics of methane hydrate in clay mineral suspensions: Differential scanning calorimetry experiments and density functional theory studies.

The investigation of methane hydrate equilibrium conditions is crucial for comprehending the occurrence of methane hydrate in marine sediments. In this study, the liquid-hydrate-vapor equilibrium condition of methane hydrate in montmorillonite and kaolinite suspensions in the presence of glycine was investigated through differential scanning calorimetry experiments. The results indicated that glycine inhibited the phase equilibrium of methane hydrate. The phase equilibrium conditions of methane hydrate in kaolinite suspension closely resembled those in pure water. In contrast, calcium montmorillonite hindered the phase equilibrium of methane hydrate owing to the presence of Ca2+. The phase equilibrium conditions of methane hydrate in kaolinite suspension with the addition of glycine were similar to those in glycine solution. The inhibitory effect of calcium montmorillonite on the phase equilibrium condition of methane hydrate intensified with the addition of glycine. Furthermore, density functional theory simulations indicated that glycine significantly reduced the binding energy between montmorillonite layers and Ca2+, potentially mitigating the inhibitory effect of Ca2+ on methane hydrate formation under suitable glycine concentrations. The diverse equilibrium conditions of methane hydrate, influenced by the types of clay minerals, salt ions, and organic matters, may play a critical role in the formation and occurrence of natural gas hydrates in marine environments, warranting exploration in future studies.

Quantification of Methane-Induced Asphaltene Precipitation in a Multiple Contact Process.

A unique experiment design is proposed to study the asphaltene precipitation caused by multiple contact processes during gas injection. The newly proposed experiment quantified the asphaltene precipitation at different methane contact steps. Twenty times methane contacts and corresponding asphaltene precipitation states are measured using a light scattering setup under reservoir condition. The amount of the asphaltene precipitation, the composition changes, and the physical properties changes are measured for the 20 times methane contacts. After verifying the asphaltene precipitation in the static experiments, the formation damage caused by the asphaltene precipitation is studied by core flooding tests for three different permeability cases. We found that the primary asphaltene precipitation mechanism in the multiple contact process during methane injection is not the composition change caused by methane extraction. The methane-induced asphaltene stability loss during the multiple contact process is vital. The size and the structure of asphaltene precipitation particles in the crude oil change with the methane contacts. We found that the mechanism of permeability reduction caused by asphaltene precipitation is different depending on the porous media pore throat size and the asphaltene precipitation particle size. Under our experimental condition, the asphaltene precipitation acts as a conformance control method, leading to well-distance optimization considerations in field applications.

An Unsteady-State Productivity Model and Main Influences on Low-Permeability Water-Bearing Gas Reservoirs at Ultrahigh Temperature/High Pressure.

Currently, there is insufficient knowledge on the development of China's low-permeability gas reservoirs under ultrahigh-temperature and high-pressure conditions; furthermore, the actual development process is difficult and has high technical demands. For example, the Ledong block in the South China Sea is a typical gas reservoir characterized using ultrahigh temperature (190 °C), high pressure (90 MPa), high water production, and low permeability (less than 1 mD). However, it is difficult to determine the factors influencing its production capacity, and the application of the traditional production capacity model is problematic because of the production of water. Accordingly, this study, which is based on the seepage theory, considers the influence of water production on the productivity of a single well; this study establishes an evaluation method for a low-permeability water-bearing gas reservoir vertical well (i.e., a highly deviated well) to determine how an unsteady state affects productivity. This method comprehensively considers stress sensitivity, initial pressure gradient, gas-water permeability, formation thickness, absolute permeability, supply radius, discharge radius, and well deviation angles to clarify the main factors affecting the productivity of single wells. Statistical methods are used to calculate and analyze the key influential factors, and this study provides quantitative evaluation methods to understand the productivity (and its influencing factors) of both vertical and highly deviated wells and the law of productivity decline. The model calculates the unblocked flow rate for 18 years as 319 × 104 m3/d. Compared with the actual production unblocked flow rate of 332 × 104 m3/d, the average error is 3.9%, which is within the allowed engineering range. Research shows the following order of factor influence on productivity: produced water-gas volume ratio > permeability > stress sensitivity coefficient > reservoir thickness > start-up pressure gradient > well deviation angle > discharge radius. Water saturation is the main factor affecting the unsteady-state productivity of gas wells in low-permeability gas reservoirs. In this study, with a production time of 100 days, the water saturation increases from 45 to 85%, and the open flow of the gas well decreases significantly from 30.1 × 104 to 1.6 × 104 m3/d, which is a decrease of 94.7%. Moreover, a continuous increase in the stress sensitivity coefficient, start-up pressure gradient, and water saturation caused a leftward shift in the inflow performance relationship curves of the modeled gas wells, whereas their production decreased.

Microscopic Mechanism of Variations in Physical Parameters of Natural Gas Containing CO2 at Ultrahigh Temperature and High Pressure.

Owing to limitations imposed by the experimental requirements, it is difficult to carry out pressure-volume-temperature experiments on CO2-containing natural gas in high-temperature and ultrahigh-pressure gas reservoirs. Relevant research is also insufficient, which has led to a lack of clarity in current understanding of the microscopic mechanism of variations in the deviation factor of high-CO2 natural gas under high-temperature and ultrahigh-pressure conditions. This has greatly limited the development of natural gas reservoirs containing CO2. To reveal the microscopic mechanism of variations in the deviation factor of natural gas containing CO2 as a function of pressure under high-temperature and high-pressure conditions, by physical simulation experiments, the deviation factors of samples of sour natural gas with known CO2 contents from the Ledong gas reservoir were determined. Then, according to the idealized parameters of the physical experiment, a molecular model of natural gas containing CO2 was established using molecular simulation methods. Changes in molecular density, molecular volume, nonbonding interaction energy, potential energy, and kinetic energy during variations in the deviation factor of a CO2-containing natural gas system as a function of pressure under high-temperature and ultrahigh-pressure conditions were quantitatively studied. Using molecular simulation techniques, it was found that the changes in total energy, kinetic energy, and potential energy between molecules are the internal factors that cause variations in the deviation factor of natural gas systems containing CO2 under ultrahigh-temperature and high-pressure conditions. The results show that the increase of carbon dioxide content in natural gas will cause the total energy of natural gas molecules to decrease when the pressure is constant. This means that the higher the CO2 content in natural gas, the easier it will be compressed. This study should lay the foundation for investigating the mechanisms of the occurrence of CO2-containing natural gas, as well as facilitating the exploitation of CO2-containing natural gas.

Investigation of dynamical properties of methane in slit-like quartz pores using molecular simulation.

The dynamical properties of adsorption media confined in micropores play an important role in the adsorptive separation of fluids. However, a problem is that it is difficult to directly use approaches based on experimental measurements. Molecular simulation has been an effective tool for investigating the diffusion of fluids on the microscale in recent years. In this work, the diffusion properties of methane in quartz were mainly investigated from a microscale viewpoint using MD (molecular dynamics) methods, and this paper primarily discusses the influence of parameters such as pressure, temperature, pore size and water content on the diffusion and thermodynamic parameters of methane in slit-like quartz pores. The results demonstrate that the transport ability of quartz pores decreases with an increase in pressure in pores of a fixed size at a certain temperature and increases with an increase in pore size or temperature at a fixed pressure, which is related to changes in the interaction between methane molecules and quartz. In the pressure range used in the simulation, the average isosteric heat of adsorption of methane increases with an increase in pressure and is in the range of 6.52-10.794 kJ mol-1. Therefore, the gas adsorption behavior is classed as physical adsorption because the heat of adsorption is significantly lower than the minimum heat of gas adsorption for chemisorption. The increase in the total adsorption entropy is caused by an increase in temperature due to an increase in internal energy, which brings about a reduction in the interactions between gas molecules and walls of quartz. However, with an increase in pore size the total adsorption entropy increases, for which an explanation may be that in pores of a larger size methane molecules are adsorbed at higher-energy sites and generate a higher isosteric heat, which causes a reduction in interactions between the adsorbate and adsorbent. Regarding the influence of different water contents on the diffusion of methane, it was demonstrated that with an increase in moisture the mobility of methane molecules initially increases and then decreases, which is related to the distance between gas molecules.

First-principles calculation of adsorption of shale gas on CaCO3 (100) surfaces.

BACKGROUND: To demonstrate the adsorption strength of shale gas to calcium carbonate in shale matrix, the adsorption of shale gas on CaCO3 (100) surfaces was studied using the first-principles method, which is based on the density functional theory (DFT). METHODS: The structures and electronic properties of CH4, C2H6, CO2 and N2 molecules were calculated by the generalized gradient approximation (GGA), for a coverage of 1 monolayer (ML). Under the same conditions, the density of states (DOS) of CaCO3 (100) surfaces before and after the adsorption of shale gas molecules at high-symmetry adsorption sites were compared. RESULTS: The results showed that the adsorption energies of CH4, C2H6, CO2 and N2 on CaCO3 (100) surfaces were between 0.2683 eV and -0.7388 eV. When a CH4 molecule was adsorbed at a hollow site and its 2 hydrogen atoms were parallel to the long diagonal (H3) on the CaCO3 (100) surface, it had the most stable adsorption, and the adsorption energy was only -0.4160 eV. The change of adsorption energy of CH4 was no more than 0.0535 eV. Compared with the DOS distribution of CH4 before adsorption, it shifted to the left overall after adsorption. At the same time, the partial density of states (PDOS) curves of CaCO3 (100) surfaces before and after adsorption basically overlapped. CONCLUSIONS: This work showed that the adsorption effect of shale gas on calcium carbonate is very weak, and the adsorption is physisorption at the molecular level.

Lactosaminated mesoporous silica nanoparticles for asialoglycoprotein receptor targeted anticancer drug delivery.

BACKGROUND: Mesoporous silica nanoparticles (MSNs) have several attractive properties as a drug delivery system, such as ordered porous structure, large surface area, controllable particle size as well as interior and exterior dual-functional surfaces. The purpose of this study was to develop novel lactosaminated mesoporous silica nanoparticles (Lac-MSNs) for asialoglycoprotein receptor (ASGPR) targeted anticancer drug delivery. RESULTS: Lac-MSNs with an average diameter of approximately 100 nm were prepared by conjugation of lactose with 3-aminopropyl triethoxysilane modified MSNs. Characterization of Lac-MSNs indicated a huge Brunauer-Emmett-Teller (BET) surface area (1012 m(2)/g), highly ordered 2D hexagonal symmetry, an unique mesoporous structure with average pore size of 3.7 nm. The confocal microscopy and flow cytometric analysis illustrated Lac-MSNs were effectively endocytosed by ASGPR-positive hepatoma cell lines, HepG2 and SMMC7721. In contrast, non-selective endocytosis of Lac-MSNs was found in ASGPR-negative NIH 3T3 cells. The cellular uptake study showed the internalization process was energy-consuming and predominated by clathrin-mediated pathway. Model drug docetaxel (DTX) was loaded in the mesopores of Lac-MSNs by wetness impregnation method. In vitro cytotoxicity assay showed that DTX transported by Lac-MSNs effectively inhibited the growth of HepG2 and SMMC7721 cells in a time- and concentration- dependent manner. CONCLUSIONS: These results demonstrated that Lac-MSNs could be a promising inorganic carrier system for targeted intracellular anti-cancer drug delivery.

Fabrication and characterization of silk fibroin-coated liposomes for ocular drug delivery.

The unique structure and protective mechanisms of the eye result in low bioavailability of ocular drugs. Using a mucoadhesive material is an efficient solution to improve ocular drug therapeutic efficacy. This study was designed to prepare a liposomal formulation coated by a novel adhesive excipient, silk fibroin (SF), for topical ocular drug delivery. The regenerated silk fibroins (SFs) with different dissolving time were coated onto the ibuprofen-loaded liposomes. The morphology, drug encapsulation efficiency, in vitro release and in vitro corneal permeation of SF-coated liposomes (SLs) were investigated in comparison with the conventional liposome. Cellular adhesion and cytotoxicity assay of SF and SLs were tested using human corneal epithelial cells (HCEC). SLs showed sustained drug release and in vitro corneal permeation of ibuprofen as compared to drug solution and conventional liposome. The cellular fluorescence appeared after 7 min of exposure to SF, and the intensity increased sustainedly up to 12h with no detectable cytotoxicity. Higher fluorescence intensity of Nile red in SLs was observed in a short period of 15 min showing a rapid uptake. These favorable properties make SF-coated liposome be a promising ocular drug delivery system.

Formulation and evaluation of novel reverse microemulsions containing salmon calcitonin in hydrofluoroalkane propellants.

To develop reverse microemulsion as a potential strategy for pulmonary delivery of salmon calcitonin (sCT) in HFA134a propellant of pressurized metered dose inhalers (pMDIs), pluronic P85 (P85) was chosen as the most appropriate surfactant to form microemulsions containing sCT. Formulation parameters, including the surfactant and ethanol content, water content, and sCT loading, were optimized to obtain two desired pMDI formulations A and B with clear and transparent appearance, Tyndall effect, good physical stability and aerosolization properties. Aerosolization properties of the optimized pMDIs were assessed by next generation impactor (NGI) and twin-stage impactor (TSI), and the dose of sCT in each stage was assayed by HPLC. The fine particle fraction (FPF) of formulations A and B were both at the range of approximately 28.0-36.0%. Cytotoxicity studies indicated the cell viability determined by MTT assay only slightly dropped when the A549 cells were exposed to the pMDI formulations. Pharmacological study performed on the male Wistar rats showed the intratracheal administration of the microemulsion pMDIs containing sCT exhibited similar but prolonged hypocalcemic activity compared with the intravenous injection of sCT solution. Therefore, such reverse microemulsions are potential for pulmonary delivery of therapeutic peptides using HFA-pMDIs.

Cubic phase nanoparticles for sustained release of ibuprofen: formulation, characterization, and enhanced bioavailability study.

In order to improve the oral bioavailability of ibuprofen, ibuprofen-loaded cubic nanoparticles were prepared as a delivery system for aqueous formulations. The cubic inner structure was verified by cryogenic transmission electron microscopy. With an encapsulation efficiency greater than 85%, the ibuprofen-loaded cubic nanoparticles had a narrow size distribution around a mean size of 238 nm. Differential scanning calorimetry and X-ray diffraction determined that ibuprofen was in an amorphous and molecular form within the lipid matrix. The in vitro release of ibuprofen from cubic nanoparticles was greater than 80% at 24 hours, showing sustained characteristics. The pharmacokinetic study in beagle dogs showed improved absorption of ibuprofen from cubic nanoparticles compared to that of pure ibuprofen, with evidence of a longer half-life and a relative oral bioavailability of 222% (P < 0.05). The ibuprofen-loaded cubic nanoparticles provide a promising carrier candidate with an efficient drug delivery for therapeutic treatment.

Process Investigation of a Novel Compaction Technique With Pellet-Containing Granules.

OBJECTIVE: The purpose of this study was to investigate the influence of the preparing process on the properties of pellet-containing granules and tablets. METHODS: Coated pellets were granulated by centrifugal granulation, and the obtained pellet-containing granules were mixed with cushioning granules and compressed into tablets. Tablets were characterized for a drug release rate as compared with the original coated pellets. RESULTS: The surface roughness and the angle of repose of pellet-containing granules increased with the granulating ratio. Weight and drug content variations in tablets were diminished by granulation, and great improvement in tablet uniformity was achieved even for large pellets. Granulation showed protection for coated films under different compress forces and at even a low content of cushioning granules. CONCLUSIONS: The uniformity of tablets prepared from pellet-containing granules could be significantly improved by the granulation process at a proper granulating ratio. The granulation process could protect the coated pellets during compaction even under high compression forces and with a low content of cushioning granules.

Molecular modeling-based inclusion mechanism and stability studies of doxycycline and hydroxypropyl-ß-cyclodextrin complex for ophthalmic delivery.

The aim of the present study was to prepare a stable complex of doxycycline (Doxy) and hydroxypropyl-ß-cyclodextrin (HPßCD) for ophthalmic delivery and investigate the inclusion mechanism and the inclusion effects on the stability of Doxy. The Doxy/HPßCD complex was prepared by solution stirring and then characterized by scanning electron microscopy and ultraviolet spectroscopy. Based on results of nuclear magnetic resonance, molecular model of Doxy/HPßCD complex was established using computational simulation of PM3 method implemented in Gaussian 03. Stabilities of Doxy/HPßCD complex in both aqueous solution and solid state at 25°C were evaluated by HPLC. Finally, in vitro antibacterial activity of the Doxy/HPßCD complex was evaluated by disk diffusion test. It was found that the stabilities of Doxy/HPßCD complex in both aqueous solution and solid state were improved obviously as compared with Doxy alone. This stability enhancement is consistent with the inclusion mechanism between HPßCD and Doxy, which showed that the unstable site of Doxy molecule at 6-CH3 was protected in the hydrophobic cavity of HPßCD, additionally, the chelation of Mg2+ provided a synergetic protection of the other unstable site of Doxy at 4-N(CH3)2. The antibacterial activity results indicated that Doxy/HPßCD complex might have potential for clinical applications.

Increasing the oral bioavailability of poorly water-soluble carbamazepine using immediate-release pellets supported on SBA-15 mesoporous silica.

BACKGROUND AND METHODS: The aim of this study was to develop an immediate-release pellet formulation with improved drug dissolution and adsorption. Carbamazepine, a poorly water-soluble drug, was adsorbed into mesoporous silica (SBA-15-CBZ) via a wetness impregnation method and then processed by extrusion/spheronization into pellets. Physicochemical characterization of the preparation was carried out by scanning electron microscopy, transmission electron microscopy, nitrogen adsorption, small-angle and wide-angle x-ray diffraction, and differential scanning calorimetry. Flowability and wettability of the drug-loaded silica powder were evaluated by bulk and tapped density and by the angle of repose and contact angle, respectively. The drug-loaded silica powder was formulated into pellets to improve flowability. RESULTS: With maximum drug loading in SBA-15 matrices determined to be 20% wt, in vitro release studies demonstrated that the carbamazepine dissolution rate was notably improved from both the SBA-15 powder and the corresponding pellets as compared with the bulk drug. Correspondingly, the oral bioavailability of SBA-15-CBZ pellets was increased considerably by 1.57-fold in dogs (P < 0.05) compared with fast-release commercial carbamazepine tablets. CONCLUSION: Immediate-release carbamazepine pellets prepared from drug-loaded silica provide a feasible approach for development of a rapidly acting oral formulation for this poorly water-soluble drug and with better absorption.

Formulation and delivery of improved amorphous fenofibrate solid dispersions prepared by thin film freezing.

The objective of this study was to prepare amorphous fenofibrate (FB) solid dispersions using thin film freezing (TFF) and to incorporate the solid dispersions into pharmaceutically acceptable dosage forms. FB solid dispersions prepared with optimized drug/polymer ratios were characterized by modulated differential scanning calorimetry (MDSC), powder X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) specific surface area measurements, Fourier-transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), and supersaturation dissolution testing. Furthermore, a dry granulation technique was used to encapsulate the TFF compositions for in vitro dissolution and in vivo animal pharmacokinetic studies. The results showed that the TFF process produced amorphous, porous, microstructured, and stable solid dispersions with high surface areas. Development of solid oral dosage forms revealed that the performance of the FB containing solid dispersions was not affected by the formulation process, which was confirmed by DSC and XRD. Moreover, an in vivo pharmacokinetic study in rats revealed a significant increase in FB absorption compared to bulk FB. We confirmed that amorphous solid dispersions with large surface areas produced by the TFF process displayed superior dissolution rates and corresponding enhanced bioavailability of the poorly water-soluble drug, FB.

[Improving the dissolution rate of poorly water-soluble resveratrol by the ordered mesoporous silica].

The aim of this study is to synthesize the ordered mesoporous silica (OMS) as drug carrier to improve release property of insoluble drug and investigate the dissolution profile of insoluble drug from the porous carrier. The OMS was obtained by using cetyltrimethyl ammonium bromide as the template and resveratrol was selected as the model drug. The resveratrol-loaded OMS (Res-OMS) were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption-desorption, X-ray diffraction (XRD) and FT-IR spectroscopy. In vitro drug release behavior was also investigated. It was found that the synthesized OMS showed a large surface area, a narrow pore size distribution and an important mesoporosity associated to hexagonally organized channels. Compared with physical mixture and crystalline powder, resveratrol was in amorphous or molecular form after loading into OMS. The release rate ofresveratrol from drug-loaded OMS was significantly increased suggesting the great potential application of OMS for the formulation of poorly soluble drugs.

In vitro and in vivo evaluation of ordered mesoporous silica as a novel adsorbent in liquisolid formulation.

BACKGROUND: A liquisolid technique has been reported to be a new approach to improve the release of poorly water-soluble drugs for oral administration. However, an apparent limitation of this technique is the formulation of a high dose because a large amount of liquid vehicle is needed, which finally results in a low-dose liquisolid formulation. Silica as an absorbent has been used extensively in liquisolid formulations. Although nanoparticle silica can be prepared and used to improve liquid adsorption capacity, loading a high dose of drug into a liquisolid is still a challenge. With the aim of improving adsorption capacity and accordingly achieving high drug loading, ordered mesoporous silica with a high surface area and narrow pore size distribution was synthesized and used in a liquisolid formulation. METHODS: Ordered mesoporous silica was synthesized and its particle size and morphology were tailored by controlling the concentration of cetyltrimethyl ammonium bromide. The ordered mesoporous silica synthesized was characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, small-angle x-ray diffraction, wide angle x-ray diffraction, and nitrogen adsorption-desorption measurements. The liquid adsorption capacity of ordered mesoporous silica was subsequently compared with that of conventional silica materials using PEG400 as the model liquid. Carbamazepine was chosen as a model drug to prepare the liquisolid formulation, with ordered mesoporous silica as the adsorbent material. The preparation was evaluated and compared with commercially available fast-release carbamazepine tablets in vitro and in vivo. RESULTS: Characterization of the ordered mesoporous silica synthesized in this study indicated a huge Brunauer-Emmett-Teller surface area (1030 m(2)/g), an ordered mesoporous structure with a pore size of 2.8 nm, and high adsorption capacity for liquid compared with conventional silica. Compared with fast-release commercial carbamazepine tablets, drug release from the liquisolid capsules was greatly improved, and the bioavailability of the liquisolid preparation was enhanced by 182.7%. CONCLUSION: Ordered mesoporous silica is a potentially attractive adsorbent which may lead to a new approach for development of liquisolid products.

Self-nanoemulsifying drug delivery system of persimmon leaf extract: Optimization and bioavailability studies.

In current study, a self-nanoemulsifying drug delivery system (SNEDDS) of persimmon (Diospyros kaki) leaf extract (PLE) was developed and characterized to compare its in vitro dissolution and relative bioavailability with commercially available tablets (Naoxinqing tablets). Pseudo-ternary phase diagrams were constructed by phase diagram by micro plate dilution (PDMPD) method, of which the evaluation method was improved to use Multiskan Ascent for identifying turbidity. The formulation of PLE-loaded SNEDDS was optimized by an extreme vertices experimental design. The optimized nanoemulsion formulation, loading with 44.48 mg/g PLE total flavonoids, consisted of Cremophor EL, Transcutol P, Labrafil M 1944 CS (56:34:10, w/w), and it remained stable after storing at 40°C, 25°C, 4°C for at least 6 months. When diluted with water, the SNEDDS droplet size was 34.85 nm and the zeta potential was -6.18 mV. Compared with the commercial tablets, the AUC of both quercetin and kaempferol, which are representative active flavonoids of PLE, was increased by 1.5-fold and 1.6-fold respectively following oral administration of PLE-loaded SNEDDS in fasting beagle dogs. These results indicate that SNEDDS is a promising drug delivery system for increasing the oral bioavailability of PLE.

Preparation and in vitro evaluation of silk fibroin microspheres produced by a novel ultra-fine particle processing system.

The objective of this study was to prepare silk fibroin SF microspheres containing the enhanced green fluorescent protein (EGFP) by using a novel ultra-fine particle processing system (UPPS) and to evaluate the microspheres as possible carriers for long-term delivery of sensitive biologicals. The drug content, encapsulation efficiency, and in vitro release were evaluated by Microplate Absorbance Reader. The particle size distribution and morphology of the microspheres were analyzed by Malvern Master Sizer 2000 and scanning electron microscopy. The distribution of EGFP and the interactions between SF and EGFP were investigated by Confocal Laser Scanning Microscopy, FTIP, Raman and NMR spectroscopy. The results showed that spherical microspheres with narrow size distribution, glossy and dense surface were successfully manufactured by using UPPS technology and over 95% of EGFP encapsulation efficiency and uniform drug distribution in the microspheres were achieved. Furthermore, a burst free and sustained release of encapsulated EGFP for a period of 50 days in deionized water was obtained. In conclusion, the novel UPPS technology could be used to manufacture SF matrix microspheres as a potential long-term protein delivery system to improve patient compliance and convenience.

Transarterial chemoembolization using docetaxel-loaded phytantriol cubic phase precursor for the treatment of hepatocellular carcinoma.

The purpose of this study was to evaluate the transarterial chemoembolic agent based on docetaxel-loaded phytantriol cubic phase precursor (DTX PCPP) by in vitro cytotoxicity study and in vivo evaluation of antitumor efficacy as well as the histological examination. The methythiazolyl tereazolium bromide assay in Hep G2 cell line revealed that DTX PCPP generated high cytotoxicity by causing cell apoptosis and G2/M phase arrest. In vivo studies conducted in rabbits bearing VX2 tumors, which were treated with DTX PCPP, used as a transarterial chemoembolic agent, showed a significant antitumor efficacy and prominent higher DTX concentrations in tumor and liver than those in other organs. The histology presented typical necrosis in tumor that demonstrated excellent therapeutic effect. In conclusion, the DTX PCPP could achieve an excellent antitumor effect with low systemic toxicity for the treatment of hepatocellular carcinoma and therefore implied the prospect of DTX PCPP for clinical applications.