Delayed Release Effect Research Articles

Enhancing activation and stability of core-shell CuZn catalyst by ZnOx oxygen vacancies for methanol steam reforming

Oxygen vacancies have been proved to be a key to catalysts’ performance in methanol steam reforming (MSR). In this work, a series of CuZn/γ-Al2O3/Al catalysts with different ZnOx oxygen vacancy content were designed to further understand effects of oxygen vacancies on the enhancement of activation and durability. Through numerical investigation and kinetic analysis, it was found that the migration energy of ZnOx on Cu was reduced by oxygen vacancies, leading to a more uniform core-shell structure and accelerated activation. By analysing the changes in valence and particle sizes of Cu species during different stages of the reaction, it was speculated that more uniform core-shell structure and Cu+ resisted Cu agglomeration, leading to a longer lifespan. Ultimately, by analyzing reduction performance and particle evolution of Cu NPs, a ‘delayed release effect’ was discovered.

Formulation Development and Evaluation of Colonspecific Esomeprazole Microspheres

The development of Esomeprazole microspheres using enteric coated polymers, such as Eudragit L100, by antisolvent precipitation method has been the focus of recent research in order to achieve the best drug concentration along with improved stability and bioavailability without any adverse effects in an acidic environment. For the development of the Esomeprazole microsphere, a 32 factorial design was used, with polymer amount and rpm being the variables. According to the results of the factorial design investigation, it was found that polymer concentration has a substantial impact on drug release while stirring speed has a large impact on entrapment efficiency. Increased Eudragit L100 concentration caused the medication release to increase from 81.06 to 95.71%. The optimized formulation was then assessed for additional research on surface morphology, particle size, PDI, Zeta potential, percent entrapment efficiency, and in-vitro investigations drug release studies and stability of prepared formulation. According to the results of scanning electron microscopy for the optimised batch, developed microparticles with smooth surfaces and spherical shapes were found. 93.40% drug release and 70.63% drug entrapment efficiency were found in the optimised batch. As a result, the current study's findings indicated that microencapsulation had significant benefits for enhancing Esomeprazole's acid stability. By providing a delayed release effect for a duration of 10 hours and a higher patient compliance rate, developed microspheres were demonstrated to be efficient for protecting drugs in acidic media.

Interaction between soybean oleosome-associated proteins and phospholipid bilayer and its influence on environmental stability of luteolin-loaded liposomes

Soybean oleosome-associated protein (SOP) plays a vital role in stabilizing soy oleosomes owing to its unique amphipathic topological structure. Inspired by the structure of natural oleosomes, in the current study, SOP-decorated liposomes (SOP-Lips) were proposed as a vehicle for improving phospholipid bilayer membrane stability. The micro morphology, size, encapsulation efficiency, and retention rate of SOP-Lips were characterized, the interactions between SOP and the phospholipid bilayer and their effects on the protein and lipid bilayer structures were evaluated. When the liposomes/SOP mass ratio was 1: 0.2 and 1: 0.4, the SOP-Lips exhibited spherical morphology and favorable dispersibility. The quartz crystal microbalance with dissipation monitoring (QCM-D) result suggested that most of SOP bound to liposomes in a tightly integrated way. Spectroscopy analysis indicated that the aromatic amino acids in the protein were exposed to a more hydrophobic microenvironment due to the interactions between the SOP and liposomes. There was an increase in α-helix and decrease in β-sheet and random curl contents in SOP upon exposure to liposomes. The decoration of SOP to liposomes could decrease membrane fluidity and enhance lateral packing of the phospholipid fatty acyl chain. The SOP coating increased the pH, ionic strength and temperature stability of luteolin liposomes (LUT-Lips). In the simulated digestion, SOP-decorated luteolin liposomes (SOP-LUT-Lips) showed a delayed release effect compared with LUT-Lips, suggesting that the inclusion of SOP resulted in a more digestion-resistant structure. This work provides a viable strategy for using SOP-Lips as a delivery system for nutraceuticals in functional food, dietary supplements and pharmaceuticals. • Soybean oleosome-associated protein (SOP) decorated liposomes were constructed. • SOP interacted with liposomes through hydrogen bonding and hydrophobic interaction. • SOP decreased phospholipid membrane fluidity and enhanced the bilayer orderness. • Inclusion of SOP increased the load efficiency of luteolin in liposomes. • SOP modified liposomes exhibited sustained luteolin release profile.

Isoniazid Microencapsulation With HPMCP HP-50 and HPMCP HP-55 (2:3) Coating Using Solvent Evaporation Method

The combination formulation of TB drugs may cause interactions if these drugs are given simultaneously. Rifampin (RIF) decomposes in the stomach when given concurrently with isoniazid (INH), which results in a decrease in the bioavailability of RIF. The purpose of this study is to make INH microcapsules using HPMCP HP-50 and HP-55 coatings to prevent these interactions. The process of making INH: HPMCP HP-50 and HP-55 (2:3) microcapsules was done by using solvent evaporation method. The entrapment efficiency of INH: HPMCP HP-50 and HP-55 (2:3) were 83.21% and 91.57%, respectively. The dissolution test of INH: HPMCP HP-50 and HP-55 microcapsules met the requirements of the Indonesian Pharmacopoeia Edition V. The FTIR test showed that the microcapsules didn’t change the chemical composition of isoniazid or the coating on the microencapsulation so that it was concluded that no chemical reaction or decomposition occurred before and after the formation of the microcapsules. Scanning Electron Microscopy (SEM) showed a spherical microcapsule surface morphology and the active substance was well coated for INH: HPMCP HP-50 (2:3), while for INH: HPMCP HP-55 (2:3) the surface of the microcapsules was round but hollow. This study produces microcapsules that can provide a delayed release effect, so it is expected that INH: HPMCP HP-50 and HP-55 (2:3) microcapsules can be released in the intestines without interacting with RIF.

Isoniazid Microencapsulation With HPMCP HP-50 and HPMCP HP- 55 (2:3) Coating Using Solvent Evaporation Method

The combination formulation of tuberculosis drugs may cause interactions if these drugs are given simultaneously. Rifampin (RIF) decomposes in the stomach when given concurrently with isoniazid (INH), which results in a decrease in the bioavailability of RIF. The purpose of this study is to make INH microcapsules using HPMCP HP-50 and HP-55 coatings to prevent these interactions. The process of making INH: HPMCP HP-50 and HP-55 (2:3) microcapsules was done by using solvent evaporation method. The entrapment efficiency of INH: HPMCP HP-50 and HP-55 (2:3) were 83.21% and 91.57%, respectively. The dissolution test of INH: HPMCP HP-50 and HP-55 microcapsules met the requirements of the Indonesian Pharmacopoeia Edition V. The FTIR results showed that there was no change either in the chemical composition of isoniazid or in the coating of the microencapsulation. Scanning Electron Microscopy (SEM) showed the active substance was well coated. This study produces microcapsules that can provide a delayed release effect, so it is expected that INH: HPMCP HP-50 and HP-55 (2:3) microcapsules can be released in the intestines without interacting with RIF.

Preparation and evaluation of sustained release dosage forms for posttransplant care

Aim: The purpose of the study was to prepare and characterize microbeads for oral sustained release of tacrolimus. Design, methodology, and approach: Tacrolimus-based microbeads were developed by ionic gelation method. Xanthan gum, chitosan, and sodium alginate were used as polymers for aqueous internal phase using calcium chloride as a cross-linking agent. The microbeads were evaluated for morphologic features by scanning electron microscopy, percentage yield, drug entrapment, and in vitro drug release. Findings and implications: Microbeads were examined for the effects of various variables in formulation process. The cross-linking reaction between sodium alginate and calcium chloride for being converted into calcium alginate in the formulation process was used in the microencapsulation of tacrolimus core material. The results showed the compatibility of the drug with the polymers in the formulation as observed in Fourier-transform infrared spectroscopy studies. The formulated microbeads showed high percentage yield and drug entrapment efficacy and the optimized formulation showed a delayed release effect following zero-order mechanism of release. Conclusion: Ionotropic gelation method was found to be a suitable method for preparing tacrolimus microbead-sustained-release drug delivery system. Chitosan and xanthan gum polymers showed potential in aiding the formulation of sustained release tacrolimus microbeads. Xanthan gum is soluble in water and confers high viscosity at low concentrations. The molecular weight of xanthan gum is more than the chitosan polymer which leads to better sustained release of microbeads prepared with xanthan gum compared to chitosan microbeads. Both chitosan and xanthan gum microbeads followed zero-order-release kinetic models.

Comparative pharmacokinetics of intravenous and intramuscular cefquinome sulfate administration in ducklings and goslings.

To compare the pharmacokinetics of cefquinome sulfate in ducklings and goslings after IV or IM administration of a single dose. 216 healthy Muscovy ducklings (Cairina moschata) and 216 healthy Sichuan white goslings (Anser cygnoides). Ducklings and goslings were each randomly assigned to 3 groups (n = 72/group) that received a single dose (2 mg/kg) of injectable cefquinome sulfate administered IV or IM or of injectable cefquinome sulfate suspension administered IM. Blood samples were collected at various points after drug administration (n = 6 birds/time point). Plasma cefquinome concentrations were measured by high-performance liquid chromatography with UV detection, and pharmacokinetic parameters were calculated with a 2-compartment model method. After IV injection, mean distribution half-life of cefquinome was longer in goslings (0.446 hours) than in ducklings (0.019 hours), whereas volume of distribution at steady state was greater (0.432 vs 0.042 L/kg) and elimination half-life was slower (1.737 vs 0.972 hours). After IM administration of injectable cefquinome sulfate, bioavailability of the drug was higher in goslings (113.9%) than in ducklings (67.5%). After IM administration of injectable cefquinome sulfate suspension, bioavailability was also higher in goslings (123.1%) than in ducklings (96.8%), whereas elimination half-life was slower (6.917 vs 1.895 hours, respectively). In goslings, IV administration of cefquinome resulted in slower distribution and metabolism of the drug than in ducklings and IM administration resulted in higher bioavailability. The delayed-release effect of the injectable cefquinome sulfate suspension when administered IM was observed only in goslings.

Exenatide-loaded inside-porous poly(lactic-co-glycolic acid) microspheres as a long-acting drug delivery system with improved release characteristics

The glucagon-like peptide-1 receptor agonist exenatide (EXT) is an effective treatment for type 2 diabetes. However, this peptide has a short biological half-life and the delayed release characteristic of current formulations limit its clinical application. Herein, we prepared EXT-loaded inside-porous poly(d,l-lactic-co-glycolic acid (PLGA) microspheres with outside layers (EXT-PMS) using a W1/O/W2 emulsion method with a microfluidic technique and its fabrication and formulation conditions were systematically investigated. In vitro dissolution experiments showed that the PLGA concentration, proportion of drug and oil phase, and the number and size of pores strongly affected the release behaviors of EXT-PMS. In vitro, the optimized EXT-PMS with large internal pores exhibited rapid and stable release without a lag phase. In a rat model, subcutaneous administration of the product yielded plasma concentrations of EXT that was sustained for 30 days with low burst and no delayed-release effect. The preparation of inside-porous microspheres is lighting up the development of long-acting drug delivery systems for other drugs with favorable release characteristics.

Preparation of aspirin sustained-release microsphere and its in vitro releasing property

OBJECTIVE It has been proven that acetylsalicylic acid (aspirin), as a kind of classical non-steroidal anti-inflammatory drug, not only has the effect of anti-inflammatory, but also has the function of immunity regulation and mineralization. However, it needs further investigation to study how to delay release of aspirin for a long time and enable to promote bone regeneration. Herein, we demonstrated that the longterm delayed release pattern of aspirin through the construction of microsphere scaffolds is promising to achieve the excellent bone regeneration. METHODS Here we synthesized three kinds of scaffolds as follows: (1) aspirin loaded calcium silicate (CaSiO3) microsphere (CaSiO3-aspirin) via simple immersion; (2) aspirin loaded polylactic-co-glycolic acid (PLGA) microsphere (PLGA-aspirin) via oil/water (O/W) emulsion; (3) aspirin loaded PLGA-CaSiO3 scaffold (PLGA-CaSiO3-aspirin) via O/W emulsion, optimal morphology and structure of PLGA-CaSiO3-aspirin scaffold was acquired through modulating the ratio between PLGA and CaSiO3. Furthermore, spectrophotometer was used to monitor the concentration of the extract of the three scaffolds for different releasing time, including 1, 2, 4, 6, 9, 13, 17, 21, 24, 30, 36, and 45 days, aspirin loading efficiency and its accumulation releasing curves were both achieved according to the concentration of aspirin. Their sustained release effects of aspirin were evaluated eventually. RESULTS Environmental scanning electron microscope (ESEM) results showed that the surface structure of the three kinds of scaffolds were smooth and had uniform size distribution. In addition, a small amount of PLGA-aspirin microspheres occurred to aggregation, while a small amount of CaSiO3-aspirin microspheres were broken. Moreover, the PLGA-aspirin microspheres in the PLGA-CaSiO3-aspirin scaffolds were uniformly adhered to the surface of CaSiO3 microspheres. The aspirin loadings of CaSiO3-aspirin, PLGA-aspirin, and PLGA-CaSiO3-aspirin were (1.06±0.04)%, (7.05±0.06)%, and (6.75±0.18)%, respectively. In addition, their corresponding time for releasing 95% of aspirin was 3, 24, and 36 days, respectively. The releasing time of PLGA-CaSiO3-aspirin was longer than that of the others and the releasing rate was more stable. CONCLUSION The microsphere scaffold of PLGA-CaSiO3-aspirin composites has excellent delayedrelease effect on aspirin, which is promising for using as osteogenic materials.

Gallic acid liposomes decorated with lactoferrin: Characterization, in vitro digestion and antibacterial activity

Gallic acid liposomes (GA-LIP) and gallic acid liposomes decorated with lactoferrin (LF-GA-LIP) were fabricated, and their physiochemical, in vitro digestion and antibacterial activity were analysed. The average particle size of LF-GA-LIP was larger than that of GA-LIP, and the former had a higher encapsulation efficiency and storage stability. Electrostatic interaction existed between lactoferrin and the phospholipid bilayer. Spherical structures of both were observed by transmission electron microscopy and atomic force microscopy. Gallic acid existed in an amorphous form in both liposomes. Hydrogen bond was formed between the hydroxyl groups of gallic acid and the polar head of phospholipid in the liposomes. LF-GA-LIP displayed a delayed-release effect compared with GA-LIP in simulated digestion. It exerted higher antibacterial properties against Escherichia coli and Staphylococcus aureus than GA-LIP. The findings suggested that the liposomes decorated with lactoferrin could be developed as a favourable delivery system for a potential application in the food industry.

Development of a safety and efficacy nanoemulsion delivery system encapsulated gambogic acid for acute myeloid leukemia in vitro and in vivo

This study aimed to improve the solubility, reduce the side effects and enhance the efficacy of gambogic acid against acute myeloid leukemia in vitro and in vivo. This oil-in-water nanoemulsion (average size 17.20 ± 0.11 nm, zeta potential 4.17 ± 0.82 mV) containing Tween-80, glycol, squalene and gambogic acid with improving 4000 times solubility was prepared by pseudoternary phase diagrams. We found that this nanoemulsion successfully encapsulated gambogic acid; it was stable and showed an obvious delayed release effect for the drug in three different phosphate-buffered saline (pH = 2.0, 5.8 and 7.4). The half inhibiting concentration (IC50) of this nanoemulsion (480.7 μg/mL and 408 μg/mL) were 1.67 times and 1.98 times higher than those of its water solution (287 μg/mL and 206 μg/mL) after acting on the toxicity standard cell line (L929 line) for 24 h and 48 h, respectively. Importantly, acute injection toxicity indicated that the half lethal dose (LD50) of this nanoemulsion (23.25 mg/kg, 95% LD50, 21.7-25.16 mg/kg) was 1.26 times higher than that of its water solution (18.59 mg/kg, 95% LD50, 16.84-20.53 mg/kg). Compared with its suspension, the bioavailability of this nanoemulsion was 318.2%. Furthermore, this nanoemulsion had a better efficacy against the acute myeloid leukemia in vitro and in vivo by improving the time and percent of survival (MV4-11 engrafts mice) and reducing half inhibiting concentration values in acute myeloid leukemia such as Jurket, HL-60 and MV4-11 cells. Our studies suggested that this nanoemulsion may be a promising therapeutic medicine for acute myeloid leukemia.

Preparation of a liposomal delivery system and its in vitro release of rapamycin.

The aim of this study was to prepare a liposomal delivery system for rapamycin and study its in vitro release characteristics. The results may provide a foundation for the further development of a liposomal delivery system for rapamycin and the establishment of a new active treatment method targeted towards the cellular components of atherosclerotic plaques. The ethanol injection method was used to prepare rapamycin-containing liposomes. The formulation was optimized by orthogonal design, and the degree of rapamycin release by the liposomes was measured by the reverse dialysis method. Orthogonal testing showed that the optimum formulation had a phospholipid concentration of 4%, a phospholipid-cholesterol mass ratio of 8:1, a drug-lipid mass ratio of 1:20 and an aqueous phase pH of 7.4. Rapamycin-containing liposomes with an encapsulation efficiency of 82.11±2.13% were prepared, and the in vitro release of rapamycin from the liposomes complied with a first-order kinetic equation. In conclusion, the formulation was optimized, the prepared liposomes had a high rapamycin encapsulation rate and good reproducibility, and their in vitro release had a certain delayed-release effect.

An automatic enzyme immunoassay based on a chemiluminescent lateral flow immunosensor

Microfluidic integrated enzyme immunosorbent assay (EIA) sensors are efficient systems for point-of-care testing (POCT). However, such systems are not only relatively expensive but also require a complicated manufacturing process. Therefore, additional fluidic control systems are required for the implementation of EIAs in a lateral flow immunosensor (LFI) strip sensor. In this study, we describe a novel LFI for EIA, the use of which does not require additional steps such as mechanical fluidic control, washing, or injecting. The key concept relies on a delayed-release effect of chemiluminescence substrates (luminol enhancer and hydrogen peroxide generator) by an asymmetric polysulfone membrane (ASPM). When the ASPM was placed between the nitrocellulose (NC) membrane and the substrate pad, substrates encapsulated in the substrate pad were released after 5.3±0.3min. Using this delayed-release effect, we designed and implemented the chemiluminescent LFI-based automatic EIA system, which sequentially performed the immunoreaction, pH change, substrate release, hydrogen peroxide generation, and chemiluminescent reaction with only 1 sample injection. In a model study, implementation of the sensor was validated by measuring the high sensitivity C-reactive protein (hs-CRP) level in human serum.

Ball Milling Synthesis of Silica Nanoparticle from Rice Husk Ash for Drug Delivery Application

Silica nanoparticles were synthesized from rice husk ash at room temperature by using high energy planetary ball mill. The milling time and mill rotational speed were varied in four levels. The morphology of the synthesized powders was investigated by the FE-SEM and TEM image as well as XRD patterns. The results have revealed that the nano-sized amorphous silica particles are formed after about 6 h ball milling and they are spherical in shape. The average particle size of the silica powders is found to be around 70 nm which decreases with increasing ball milling time or mill rotational speed. The as-synthesized silica nanoparticles were subsequently employed as drug carrier to investigate in vitro release behavior of Penicillin-G in simulated body fluid. UV-Vis spectroscopy was used to determine the amount of Penicillin-G released from the carrier. Penicillin-G release profile from silica nanoparticles exhibited a delayed release effect.

Preparation and Characterization of Folate-Decorated Chitosan Microspheres as a Sustained-Release Drugs Carrier

Folic acid-chitosan (FA-CTS) and 10-hydroxycamptothecin (HCPT)-loaded folate-conjugated chitosan (FA-CTS/HCPT) microspheres were prepared by the ionic crosslinking method.The morphological characteristics of microspheres were examined using a scanning electron microscope (SEM). The average particle size and size distribution were determined by dynamic light scattering. The drug encapsulation efficiency (EE) , loading capacity (LC)and release characteristics in vitro were determined using ultraviolet spectrophotometer.The results shown that the microspheres are uniform spherical and regular with a size between 19.79 and81.40μm.Optimized preparation parameters lead to the successful preparation of hydroxycamptothecin-loaded folate-conjugated chitosan microspheres characterized with encapsulation efficiency and loading capacity up to (86.8±0.1)% and 20.6±0.3 % respectively. More then 90% of 10-hydroxycamptothecin was released from microspheres in 4 h at artificial gastric juice, 8h at artificial small intestinal fluid with a good delayed release effect.

Investigation of In Vitro Drug Release from Porous Hollow Silica Nanospheres Prepared of ZnS@SiO2Core-Shell

In this contribution, porous hollow silica nanoparticles using inorganic nanosized ZnS as a template were prepared. The hydrothermal method was used to synthesize pure ZnS nanospheres material. The ZnS@SiO2 core-shell nanocomposites were prepared using a simple sol-gel method successfully. The hollow silica nanostructures were achieved by selective removal of the ZnS core. The morphology, structure, and composition of the product were determined using powder X-ray diffraction (XRD), emission scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FT-IR). The results demonstrated clearly that the pure ZnS nanoparticles are in a spherical form with the average size of 40 nm and correspond with zinc blend structure. The porous hollow silica nanoparticles obtained were exploited as drug carriers to investigate in vitro release behavior of amoxicillin in simulated body fluid (SBF). UV-visible spectrometry was carried out to determine the amount of amoxicillin entrapped in the carrier. Amoxicillin release profile from porous hollow silica nanoparticles followed a three-stage pattern and indicated a delayed release effect.

Synthesis and characterization of porous hollow silica nanoparticles using ZnSe core as template for drug delivery application

In this contribution, porous hollow silica nanoparticles using inorganic nano sized ZnSe as template were prepared. The hydrothermal method was used to synthesize pure ZnSe nanospheres material. The ZnSe/SiO2 core-shell nanocomposites were prepared using a simple sol-gel method successfully. The hollow silica nanostructures were achieved by selective removal of the ZnSe core. The morphology, structure and composition of the product were determined using powder X-ray diffraction (XRD), emission scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FT-IR). The results demonstrated clearly that the pure ZnSe nanoparticles are in a spherical form with the average size of 30 nm and correspond with zinc blend structure. The porous hollow silica nanoparticles obtained were exploited as drug carrier to investigate in vitro release behavior of cefalexin in simulated body fluid (SBF). UV-Visible spectrometry was carried out to determine the amount of cefalexin entrapped in the carrier. Cefalexin release profile from porous hollow silica nanoparticles followed a three stage pattern and indicated a delayed release effect.

Formulation, preparation and evaluation of flunarizine-loaded lipid microspheres

The aim of this study was to investigate the feasibility of preparing flunarizine-loaded lipid microspheres. Lipid microspheres (LMs) are excellent drug carriers for drug delivery systems (DDS) and are relatively stable and easily mass-produced. They have no particular adverse effects. LMs have been widely studied as drug carriers for water-soluble drugs, lipid-soluble drugs and inadequately soluble (in water or in lipid) drugs, in that they have a lipid layer, a water layer and an emulsifier layer. Flunarizine (FZ), a poorly water-soluble drug, was incorporated in lipid microspheres to reduce side effects by avoiding the use of supplementary agents, compared with solution injection. After investigation, the final formulation was as follows: 10% oil phase (long-chain triglyceride (LCT); medium-chain fatty acid (MCT) = 50:50); 1.2% egg lecithin; 0.2% Tween-80; 2.5% glycerin; 0.3% dl-alpha-tocopherol; 0.02% EDTA; 0.03% sodium oleate; 0.1% FZ and double-distilled water to give a total volume of 100 mL. Homogenization was the main method of preparation and the best conditions were a temperature of 40 degrees C, a pressure of 700-800 bar and a suitable cycle frequency of about 10. The particle size distribution, zeta-potential and entrapment efficacy were found to be 198.7+/-54.0 nm, -26.4 mV and 96.2%, respectively. Its concentration in the preparation was 1.0 mg mL(-1). The lipid microspheres were stable during storage at 4 degrees C, 25 degrees C and 37 degrees C for 3 months. Pharmacokinetic studies were performed in rats using a dose of 1.0 mg kg(-1). The pharmacokinetic parameters were as follows: AUC(0-t) 6.13 mug.h mL(-1), t(1/2) 5.32 h and Ke 0.16 L h(-1). The preparation data fitted a two-compartment model estimated by using 3p87 analysis software. From the observed data, FZ encapsulated in LMs did not significantly alter the pharmacokinetic characteristic compared with the FZ solution injection and did not produce a delayed release effect, when it was released in-vivo in rats. However, the availability of the drug was increased. These results suggested that this LM system is a promising option for the preparation of the liquid form of FZ for intravenous administration.

Lyophilized Cheliensisin A submicron emulsion for intravenous injection: Characterization, in vitro and in vivo antitumor effect

Growing attentions have been focused on natural antitumor drugs. Recently, a novel and potent antitumor drug Cheliensisin A (GC-51) with broad-spectrum efficiency has been developed. However, due to its poor water solubility and chemical instability, choosing the appropriate dosage form is of great significance. This study aimed at developing a lyophilized submicron emulsion for GC-51 and further improving the therapeutic index of the drug. The resultant lyophilized GC-51 submicron emulsion was much more stable than its solution, which can be stored for years without significant change on physicochemical properties. And its solubility was increased from 6.74 ± 0.14 to 2.00 ± 0.10 mg mL −1. The 50% inhibitory concentration IC 50 values were calculated from growth curves by MTT assay on various tumor cell lines. Compared with the IC 50 of GC-51 crude drug, that of lyophilized GC-51 submicron emulsion decreased from 24.04 ± 1.97 to 8.23 ± 1.84 μg mL −1 on HepG2, and from 31.08 ± 2.56 to 10.85 ± 2.09 μg mL −1 on CT-26, from 17.90 ± 1.83 to 7.49 ± 1.87 μg mL −1 on HeLa and from 16.38 ± 2.41 to 10.13 ± 2.12 μg mL −1 on A549, respectively. In the time-dependent assay of tumor cell viability, lyophilized GC-51 submicron emulsion exhibited significantly lower inhibition rate in the initial action times, but increased gradually afterwards. That means lyophilized submicron emulsion as the vector for GC-51 had some protective and delayed release effect. Further, the in vivo therapeutic efficacy was measured in pulmonary metastasis of colon cancer-bearing BALB/c mice model. An obvious enhanced antitumor activity was observed after administration of lyophilized GC-51 submicron emulsion ( P < 0.05), which increased from 22.78 ± 3.5 to 41.42 ± 4.2% compared with GC-51 injection. And the life span of tumor-bearing mice in lyophilized GC-51 submicron emulsion group was significantly longer than that of the mice in GC-51 injection and normal saline groups. Compared with crude drug, the lyophilized GC-51 submicron emulsion showed a significantly higher antitumor efficiency both in vivo and in vitro, suggesting a potential application in tumor chemotherapy.

Preparation and characterization of porous hollow silica nanoparticles for drug delivery application

Porous hollow silica nanoparticles (PHSNP) with a diameter of 60–70 nm and wall thickness of approximately 10 nm were synthesized by using CaCO 3 nano-particles as the inorganic template. The characterization of PHSNP by TEM and BET indicated that PHSNP were uniform spherical particles with good dispersion, and had a specific surface area of 867 m 2/g. The as-synthesized PHSNP were subsequently employed as drug carrier to investigate in vitro release behavior of cefradine in simulated body fluid. UV-spectrometry and TG analyses were performed to determine the amount of cefradine entrapped in the carrier. The BJH pore size distribution of PHSNP before and after entrapping cefradine was examined. Cefradine release profile from PHSNP followed a three-stage pattern and exhibited a delayed release effect.