Solid carriers had important effects on the properties of solid self-microemulsifying drug delivery systems (S-SMEDDS). In order to make the basis for further development of S-SMEDDS, the influences of silica on the absorption of S-SMEDDS were investigated. An in vitro lipolysis model was used to evaluate the influence of silica on self-microemulsifying drug delivery system digestion from intestinal tract. S-SMEDDS containing silica were prepared by extrusion/spheronization. The drug release and absorption were investigated. The results showed that lipolysis rate and drug concentration in aqueous phase after intestinal lipolysis both increased by adding silica, which was benefit to drug absorption. And silica was not benefit to absorption for slowing drug release. Consistently, there was no significant influence of silica on intestinal absorption. This study implied that the influences of silica on lipolysis rate and drug release were both amount dependent and it is suggested that silica could be used as the solid carrier but the proportion needs to be optimized.
Animals ; Biological Availability ; Drug Delivery Systems ; methods ; Emulsions ; Indomethacin ; administration & dosage ; pharmacokinetics ; Intestinal Absorption ; Lipolysis ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; administration & dosage ; chemistry ; Solubility

Mesoporous silica nanoparticles as drug carrier have become the new hot point in the field of biomedical application in recent years. This review focuses on the more recent developments and achievements on experimental design aspect of mesoporous silica nanoparticles with cancer diagnosis and therapy. The key advances of functionalization strategies of mesoporous silica nanoparticles with controlled release, tumor targeting and overcoming multidrug resistance are discussed in particular. Mesoporous silica nanoparticles as unique delivery systems have the potential to provide significantly a sound platform for cancer theranostic application.
Animals ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Delayed-Action Preparations ; Drug Carriers ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Nanoparticles ; Neoplasms ; diagnosis ; therapy ; Porosity ; Silicon Dioxide

OBJECTIVETo investigate the pulmonary toxicity of different concentrations of nano-silica (nano-SiO2) under continuous dynamic inhalation conditions in the rat.

METHODS48 male Sprague-Dawley rats were randomly divided into four groups, including the dispersant control group (saline) and nano-SiO2 low-dose group (0.3%, w/v), the middle-dose group (1%) and the high-dose group (3%). Animals were sacrificed at 28 d after exposure under continuous dynamic inhalation conditions, and bronchoalveolar lavage fluid (BALF) and lung tissue were collected. And following items were observed: body coefficient, BALF related items (leukocytes and classification, total protein content, LDH activity), lung tissue pathological changes (HE staining), and pulmonary fibrosis forming (collagen fiber VG staining).

RESULTSCompared to the dispersant control group, there was no significant change on lung organ coefficient in Nano-SiO2 group (P < 0.05). The BALF total WBC count in 1% and 3% in nano-SiO2 groups showed higher value than the dispersant control group (P < 0.05). No obvious changes were found on total protein content and LDH activity in nano-SiO2 groups compared to the dispersant control group (P > 0.05). For differential WBC counts, lymphocyte count in BALF in nano-SiO2 groups was significantly decreased (P < 0.05), monocyte and macrophage counts were significantly increased (P < 0.05), but there was no difference on the proportion of neutrophils (P > 0.05). HE staining results showed that the obvious thickening of alveolar wall in nano-SiO2 groups, inflammatory cell infiltration also increased around the bronchial and vascular wall. Lung fibrosis VG staining showed no significant change of collagen fiber distribution.

CONCLUSIONUnder our experimental conditions, the continuous dynamic inhalation of nano-SiO2 only caused the significant inflammation in rat lungs, pulmonary fibrosis phenomenon could not be observed significantly.

Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Inhalation Exposure ; Lung ; drug effects ; metabolism ; pathology ; Male ; Pulmonary Fibrosis ; chemically induced ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; administration & dosage ; toxicity

OBJECTIVETo investigate the subchronic oral toxicity of silica nanoparticles (NPs) and silica microparticles (MPs) in rats and to compare the difference in toxicity between two particle sizes.

METHODSSprague-Dawley rats were randomly divided into seven groups: the control group; the silica NPs low-, middle-, and high-dose groups; and the silica MPs low-, middle-, and high-dose groups [166.7, 500, and 1,500 mg/(kg•bw•day)]. All rats were gavaged daily for 90 days, and deionized water was administered to the control group. Clinical observations were made daily, and body weights and food consumption were determined weekly. Blood samples were collected on day 91 for measurement of hematology and clinical biochemistry. Animals were euthanized for necropsy, and selected organs were weighed and fixed for histological examination. The tissue distribution of silicon in the blood, liver, kidneys, and testis were determined.

RESULTSThere were no toxicologically significant changes in mortality, clinical signs, body weight, food consumption, necropsy findings, and organ weights. Differences between the silica groups and the control group in some hematological and clinical biochemical values and histopathological findings were not considered treatment related. The tissue distribution of silicon was comparable across all groups.

CONCLUSIONOur study demonstrated that neither silica NPs nor silica MPs induced toxicological effects after subchronic oral exposure in rats.

Administration, Oral ; Animals ; Dose-Response Relationship, Drug ; Female ; Male ; Nanoparticles ; toxicity ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; toxicity ; Toxicity Tests, Subchronic

This study plans to prepare lipid bilayer-coated mesoporous silica nanoparticles (LMSNs) which are pH sensitive with core-shell structure to improve the tumor cell lethality of antitumor drug. The lipid coated mesoporous silica nanoparticles loaded with irinotecan (CPT-11) (CPT-11-LMSNs) were prepared by hot water-film hydration method, and the characterized its morphology, particle size and release in vitro. Meanwhile, the intracellular uptake and cell toxicity of CPT-11-LMSNs and intracellular accumulation of CPT-11 were evaluated on human breast carcinoma cell line (MCF-7). The results indicated that the mean diameter of the spherical LMSNs was (120.27 +/- 5.91) nm. The slow release in simulated normal physiological conditions and a rapid release under simulated intracellular condition demonstrated the pH sensitivity of CPT-11-MSNs in vitro. Moreover, the CPT-11-LMSN could improve the intracellular CPT-11 cumulant 2.1 times and reduce half maximal inhibitory concentration (IC50) values of CPT-11 1.4 times compared with CPT-11-MSNs, demonstrating a stronger cell lethality.
Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Camptothecin ; administration & dosage ; analogs & derivatives ; pharmacology ; Cell Proliferation ; drug effects ; Drug Carriers ; Humans ; Hydrogen-Ion Concentration ; Lipid Bilayers ; administration & dosage ; chemistry ; MCF-7 Cells ; Nanoparticles ; Particle Size ; Porosity ; Silicon Dioxide ; administration & dosage ; chemistry

The aim of this study is to investigate the feasibility of silica-coated ethosome as a novel oral delivery system for the poorly water-soluble curcumin (as a model drug). The silica-coated ethosomes loading curcumin (CU-SE) were prepared by alcohol injection method with homogenization, followed by the precipitation of silica by sol-gel process. The physical and chemical features of CU-SEs, and curcumin release were determined in vitro. The pharmacodynamics and bioavailability measurements were sequentially performed. The mean diameter of CU-SE was (478.5 +/- 80.3) nm and the polydispersity index was 0.285 +/- 0.042, while the mean value of apparent drug entrapment efficiency was 80.77%. In vitro assays demonstrated that CU-SEs were significantly stable with improved release properties when compared with curcumin-loaded ethosomes (CU-ETs) without silica-coatings. The bioavailability of CU-SEs and CU-ETs was 11.86- and 5.25-fold higher, respectively, than that of curcumin suspensions (CU-SUs) in in vivo assays. The silica coatings significantly promoted the stability of ethosomes and CU-SEs exhibited 2.26-fold increase in bioavailablity relative to CU-ETs, indicating that the silica-coated ethosomes might be a potential approach for oral delivery of poorly water-soluble drugs especially the active ingredients of traditional Chinese medicine with improved bioavailability.
Administration, Oral ; Animals ; Biological Availability ; Coated Materials, Biocompatible ; chemistry ; Curcumin ; administration & dosage ; chemistry ; pharmacokinetics ; Drug Carriers ; Ethanol ; chemistry ; Liposomes ; chemistry ; Male ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; chemistry ; Solubility

OBJECTIVETo investigate the pharmacological effect of Nyctanthes arbortristis (NAT) leaf extract in the prevention of lung injury induced by silica particles.

METHODLung injury was induced in Swiss mice through inhalation exposure to silica particles (< 5 mu) using a Flow Past Nose Only Inhalation Chamber at the rate of -10 mg/m3 respirable mass for 5 h. Lung bronchoalveolar lavage (BAL) fluid collected between 48 and 72 h was subjected to protein profiling by electrophoresis and cytokine evaluation by solid phase sandwich ELISA. Lung histopathology was performed to evaluate lung injury.

RESULTSInhalation of silica increased the level of tumor necrosis factor-alpha (TNF-alpha), and of the 66 and 63 kDa peptides in the BAL fluid in comparison to sham-treated control. Pre-treatment of silica exposed mice with NAT leaf extract significantly prevented the accumulation of TNF-alpha in the BAL fluid, but the 66 and 63 kDa peptides remained unchanged. The extract was also effective in the prevention of silica-induced early fibrogenic reactions like congestion, edema and infiltration of nucleated cells in the interstitial alveolar spaces, and thickening of alveolar septa in mouse lung.

CONCLUSIONNAT leaf extract helps in bypassing silica induced initial lung injury in mice.

Administration, Oral ; Animals ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Inhalation Exposure ; Male ; Mice ; Oleaceae ; chemistry ; Phytotherapy ; Plant Extracts ; pharmacology ; Pulmonary Fibrosis ; etiology ; prevention & control ; veterinary ; Silicon Dioxide ; adverse effects ; Silicosis ; prevention & control ; veterinary

OBJECTIVETo explore the effects of high-dose N-acetylcysteine on the lung tissues of rats exposed to silica.

METHODSNinety-six Wistar rats were randomly divided into model group, intervention group and control group (32 rats for each group). The rats of model group and intervention group were exposed to silica by intratracheal infusion of silica dust suspension. The rats in the intervention group were orally given high dose N-acetylcysteine. In 3, 7, 14, 28 days after exposure, eight rats in each group were sacrificed, respectively and the lung samples were collected. The pathological changes of lung were evaluated by HE and Masson staining methods. The levels of TNF-alpha and IL-8 in the BALF were detected by ELISA.

RESULTSCompared with the control group, the alveolitis and pulmonary fibrosis in the intervention group were significantly reduced. In 3, 7, 14, 28 days after exposure, the lung/body coefficients in the intervention group were 9.30 +/- 0.78, 6.29 +/- 0.74, 7.63 +/- 0.88, 6.06 +/- 1.16 respectively, which were significantly lower than those (13.84 +/- 1.61, 9.23 +/- 0.87, 11.23 +/- 1.25, 9.56 +/- 0.76, P < 0.01 ) in the model group (P < 0.01). At the different time points, the levels of TNF-alpha and IL-8 in the BALF in the intervention group were significantly higher than those in the control group (P < 0.01), but were significantly lower than those in the model group (P < 0.01).

CONCLUSIONThe intervention with high dose N-acetylcysteine can significantly reduce the alveolitis and the TNF-alpha and IL-8 levels in the BALF, therefore, inhibit and delay the development of pulmonary fibrosis of rats exposed to silicon dioxide.

Acetylcysteine ; administration & dosage ; pharmacology ; Animals ; Bronchoalveolar Lavage Fluid ; Dose-Response Relationship, Drug ; Dust ; Interleukin-8 ; metabolism ; Lung ; drug effects ; pathology ; Male ; Pulmonary Fibrosis ; chemically induced ; metabolism ; Rats ; Rats, Wistar ; Silicon Dioxide ; adverse effects ; Tumor Necrosis Factor-alpha ; metabolism

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.
Drug Carriers ; Drug Compounding ; Drug Delivery Systems ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Porosity ; Silicon Dioxide ; chemistry ; Solubility ; Spectroscopy, Fourier Transform Infrared ; Stilbenes ; administration & dosage ; chemistry ; X-Ray Diffraction

OBJECTIVE: To construct mesoporous nano-bioactive glass (MNBG) microspheres load-release minocycline as an antibacterial drug delivery system. METHODS: Sol-gel method was used to synthesze MNBG microspheres as drug carrier. The MNBG consisted of SiO2, CaO, and P2O5. According to the content of silicon, MNBG microspheres were divided into four groups (60S, 70S, 80S and 90S). Scanning electron microscopy (SEM) was used to observe the surface characteristic and particle size of MNBG; Nitrogen adsorption-desorption experiment was performed to calculate the MNBG's specific surface area and the pore sizes; The Fourier transform infrared spectrum (FT-IR) and the thermogravimetric analysis were conducted to calculate the loading efficiencies of minocycline hydrochloride; UV spectrophotometric was used to determine the cumulative release of minocycline from drug-loaded particles in PBS solution within 21 d. Agar diffusion test (ADT) was performed to evaluate the antibacterial properties on Enterococcus faecalis. The inhibition zone was observed and the diameter was measured. RESULTS: The MNBG microspheres had good dispersion, large surface area, and even particle size. The pore sizes ranged from 4.77 nm to 7.33 nm. The loading experiment results showed that the minocycline hydrochloride loading efficiency of MNBG was related to the pore size of the microspheres. Among 60S, 70S, 80S and 90S, 60S MNBG had the highest loading efficiency of 16.33% due to its high calcium content and large pore sizes. A slow minocycline release rate from MNBG particles in PBS solution until d 21 was observed. It was showed that a burst release of 28% of the total drug for the first 24 h. A cumulative release of 35% was found, and the final concentration of minocycline maintained at about 47 mg/L. ADT showed that mino-MNBG had inhibitory effect on the growth of Enterococcus faecalis. 1 g/L minocycline, 1 g/L mino-MNBG, and 0.1 g/L minocycline presented inhibition zone, however, PBS and 1 g/L MNBG didn't. The diameter of the inhibition zone of minocycline groups was significant larger than that of mino-MNBG group (P<0.05), which was also significant larger than those of PBS and MNBG groups (P<0.05). It showed that mino-MNBG drug delivery system had antibacterial properties on Enterococcus faecalis. CONCLUSION The 60S MNBG that can effectively load and release minocycline may be an ideal drug carrier.
Adsorption ; Anti-Bacterial Agents/administration & dosage* ; Drug Carriers ; Drug Delivery Systems ; Glass ; Microscopy, Electron, Scanning ; Microspheres ; Minocycline/adverse effects* ; Nitrogen ; Particle Size ; Porosity ; Silicon Dioxide ; Spectroscopy, Fourier Transform Infrared