Qinfu Zhao

Shenyang Pharmaceutical University, Feng-t’ien, Liaoning, China

Are you Qinfu Zhao?

Claim your profile

Publications (17)39.38 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In the past decade, mesoporous silica nanoparticles (MSNs) with a large surface area and pore volume have attracted considerable attention for their application in drug delivery and biomedicine. In this review, we highlight the recent advances in silica-assisted drug delivery systems, including (1) MSN-based immediate/sustained drug delivery systems and (2) MSN-based controlled/targeted drug delivery systems. In addition, we summarize the biomedical applications of MSNs, including (1) MSN-based biotherapeutic agent delivery; (2) MSN-assisted bioimaging applications; and (3) MSNs as bioactive materials for tissue regeneration.
    Nanomedicine: Nanotechnology, Biology and Medicine. 11/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Novel multifunctional porous titanium dioxide (TiO2) nanoparticles modified with polyethylenimine (PEI) were developed to explore the feasibility of exploiting the photocatalytic property of titanium dioxide to achieve ultraviolet (UV) light-triggered drug release. Additionally, in order to further realize targeting delivery, folic acid (FA) which chemically conjugated to the surface of the functionalized multifunctional porous TiO2 nanoparticles through amide linkage with free amine groups of PEI was used as a cancer-targeting agent to effectively promote cancer cell-specific uptake through receptor-mediated endocytosis. And a typical poorly water-soluble anti-cancer drug, paclitaxel, was encapsulated in multifunctional porous TiO2 nanoparticles. The PEI on the surface of multifunctional porous TiO2 nanoparticles could effectively block channel to prevent premature drug release and thus providing enough circulation time to target cancer cells. Following UV light radiation, PEI molecules on the surface were cut off by the free radicals (OH• and O2-) TiO2 produced and then the drug loaded in the carrier was released rapidly into the cytoplasm. Importantly, the amount of the drug released from multifunctional porous TiO2 nanoparticles can be regulated by UV light-radiation time to further control the anti-cancer effect. This multifunctional porous TiO2 nanoparticle exhibits a combination of stimuli-triggered drug release and cancer cell targeting. We believe that the present study will provide important information for the use of porous TiO2 nanomaterials in light-controlled drug release and targeted therapy.
    Acta Biomaterialia. 11/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: To meet the needs of targeted drug delivery and medical imaging, uniform mesoporous carbon spheres (UMCS) were functionalized using hyperbranched polyethyleneimine (PEI) covalently linked with fluorescein isothiocyanate (FITC) and folic acid (FA). Folate-receptor-positive KB cancer cells internalized five times more nanoparticles than A549 cells deficient in folate receptors in vitro using flow cytometry and confocal microscopy. The in vivo distribution results also confirmed that the FA–PEI–FITC–UMCS nanoparticles could target the FA-positive tumors. In addition, the specifically targeted hybrid carbon nanoparticles exhibited non-cytotoxic and controlled intracellular release (pH dependent) of the loaded agents. The in vivo antitumor effect of the paclitaxel (PTX)-loaded nanoparticles was investigated in Kunming mice harboring a hepatic H22 tumor. PTX-loaded FA–PEI–UMCS nanoparticles displayed superior antitumor effects compared to other PTX formulations, and the tumor growth inhibition rate was 86.53% compared with the control group (saline) for the enhanced targeted accumulation of NPs in tumor cells.
    Carbon 11/2014; 79:123–134. · 6.16 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this paper, we describe the development of a redox-responsive delivery system based on 6-mercaptopurine (6-MP)-conjugated colloidal mesoporous silica (CMS) via disulfide bonds. mPEG was modified on the surface of silica to improve the dispersibility and biocompatiblity of CMS by reducing hemolysis and protein adsorption. The CMS carriers with different amounts of thiol groups were prepared to evaluate the impact of modified thiol on the drug loading efficiency. In vitro release studies demonstrated that the CMS nanoparticles exhibited highly redox-responsive drug release. The cumulative release of 6-MP was less than 3% in absence of GSH, and reached more than 70% within 2h in the presence of 3mM GSH. In addition, by comparing the cumulative release profiles of CMS-SS-MP@mPEG with their counterparts without the grafting of hydrophilic PEG, it was found that mPEG chains did not hinder the drug release due to the cleavable disulfide bonds and the improved dispersibility. Overall, this work provides a new strategy to connect thiol-containing/thiolated drugs and hydrophilic polymers to the interior and exterior of silica via disulfide bonds to obtain redox-responsive release and improve the dispersibility and biocompatibility of silica. Copyright © 2014 Elsevier B.V. All rights reserved.
    International Journal of Pharmaceutics 10/2014; 477(1-2):613-622. · 3.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We used a combination of mesoporous silica nanospheres (MSN) and layer-by-layer (LBL) self-assembly technology to establish a new oral sustained drug delivery system for the poorly water-soluble drug felodipine. Firstly, the model drug was loaded into MSN, and then the loaded MSN were repeatedly encapsulated by chitosan (CHI) and acacia (ACA) via LBL self-assembly method. The structural features of the samples were studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption. The encapsulating process was monitored by zeta-potential and surface tension measurements. The physical state of the drug in the samples was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). The influence of the multilayer with different number of layers on the drug release rate was studied using thermal gravimetric analysis (TGA) and surface tension measurement. The swelling effect and the structure changes of the multilayer were investigated to explore the relationship between the drug release behavior and the state of the multilayer under different pH conditions. The stability and mucosa adhesive ability of the prepared nanoparticles were also explored. After multilayer coating, the drug release rate was effectively controlled. The differences in drug release behavior under different pH conditions could be attributed to the different states of the multilayer. And the nanoparticles possessed good stability and strong mucosa adhesive ability. We believe that this combination offers a simple strategy for regulating the release rate of poorly water-soluble drugs and extends the pharmaceutical applications of inorganic materials and polymers.
    Materials Science and Engineering: C. 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: A redox-responsive delivery system based on colloidal mesoporous silica (CMS) has been developed, in which 6-mercaptopurine (6-MP) was conjugated to vehicles by cleavable disulfide bonds. The oligosaccharide of hyaluronic acid (oHA) was modified on the surface of CMS by disulfide bonds as a targeting ligand and was able to increase the stability and biocompatiblity of CMS under physiological conditions. In vitro release studies indicated that the cumulative release of 6-MP was less than 3 % in the absence of GSH, and reached nearly 80 % within 2 h in the presence of 3 mM GSH. Confocal microscopy and fluorescence-activated cell sorter (FACS) methods were used to evaluate the cellular uptake performance of FITC labelled CMS, with and without oHA modification. The CMS-SS-oHA exhibited a higher cellular uptake performance via CD44 receptor-mediated endocytosis in HCT-116 (CD44 receptor-positive) cells than in NIH-3T3 (CD44 receptor-negative) cells. 6-MP loaded CMS-SS-oHA exhibited greater cytotoxicity against HCT-116 cells than NIH-3T3 cells due to the enhanced cell uptake behavior of CMS-SS-oHA. This study provides a novel strategy to covalently link bioactive drug and targeting ligand to the interiors and exteriors of mesoporous silica to construct a stimulus-responsive targeted drug delivery system.
    ACS Applied Materials & Interfaces 10/2014; · 5.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this study, phosphonate-terminated magnetic mesoporous nanoparticles (pMMSNs) was designed by incorporation of MNPs in the center of mesoporous silica nanoparticles (MSNs) and followed by grafting phosphonate group on to the surface of MMSNs. The carrier exhibited a typical superparamagnetic feature and the saturation magnetization was 4.89 emu/g measured by vibrating sample magnetometer (VSM). pMMSNs had a spherical morphology and a pore size of 2.2 nm. From N2 adsorption-desorption analysis, pMMSNs had a surface area of 613.4 m2/g and a pore volume of 0.78 cm3/g. Phosphonate modification improved the colloidal stability of MMSNs, and the hydrodynamic diameter of pMMSNs was around 175 nm. The hydrophilic phosphonate group significantly enhanced the negative surface charge of MMSNs from -19.3 mV to -28.8 mV. pMMSNs with more negative surface charge had a 2.3-fold higher drug loading capacity than that of MMSNs. In addition, the rate and amount of release of doxorubicin (DOX) from DOX/pMMSNs was pH-dependent and increased with the decrease of pH. At pH 7.4, the release amount was quite low and only approximately 17 wt% of DOX was released in 48 h. At pH 5.0 and 3.0, the release rate increased significantly and the release amount achieved 31 wt% and 60 wt% in 48 h, respectively. To evaluate the magnetic targeting performance of pMMSNs, FITC labeled pMMSNs was injected into mice bearing S180 solid tumor. FITC labeled pMMSNs controlled by an external magnetic field showed higher tumor accumulation and lower normal tissue distribution.
    Asian Journal of Pharmaceutical Sciences 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Uniform mesoporous carbon spheres (UMCS) were used as a carrier to improve the bioavailability of the model drug, celecoxib (CEL). Furthermore, we investigated the mechanism responsible for the improved bioavailability of CEL. The association, adhesion and uptake of UMCS by intestinal epithelial cells were studied by transmission electron microscopy (TEM), fluorescence-activated cell sorting (FACS) and laser confocal scanning microscopy (LCSM). UMCS was found to promote cellular uptake of CEL. Drug transport in Caco-2 cell monolayers proved that UMCS can significantly reduce the rate of drug efflux and improve CEL permeability. The dissolution rate of CEL from drug-loaded samples was markedly improved compared with pure crystalline CEL; moreover, oral bioavailability of CEL loaded into UMCS was also markedly improved compared with that of commercially available capsules. UMCS indicates the advantages and potential of this method to achieve improved oral absorption by increasing the dissolution rate, cellular uptake and permeability of the drug.
    Drug delivery. 05/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the current study, mesoporous carbon (MC) with pore volume (1.53 cm3/g) and pore size (9.74 nm) was successfully prepared as a carrier for celecoxib (CEL). Celecoxib was loaded into the pore channels of MC using three different methods: solvent evaporation method, absorption method and physical mixing method. Solid-state characterization methods, such as SEM, TEM, BET, DSC and XRD were used to systematically investigate the process of the drug loading system. Dissolution tests were performed to examine the effects of MC on the release of CEL. Furthermore, the cytotoxicity, wound healing, migration and invasion experiments were carried out to measure the contribution of MC to the anti-tumor metastasis ability of celecoxib on MDA-MB-231 cells. The results showed that CEL could be kept in a non-crystalline state when they were incorporated into the MC using the solvent evaporation method or absorption method. The dissolution rate of CEL released from MCS (Mesoporous carbon – Celecoxib – Solvent evaporation method) and MCA (Mesoporous carbon – Celecoxib – Absorption evaporation method) was all significantly higher than that of pure CEL. The cumulative release for MCS within the 5 min was up to 51.86%. MCS enhanced the inhibitory effect of CEL on the migration and invasion of MDA-MB-231 cells.
    Asian Journal of Pharmaceutical Sciences 04/2014; 9(2):82–91.
  • [Show abstract] [Hide abstract]
    ABSTRACT: 3-D ordered macroporous (3DOM) materials were customized for BSA adsorption and further oral immunization. These carriers have a high adsorption capacity and our customized carrier showed a distinctive double-plateau adsorption behavior. Different BSA release rates (between the two plateaus) could be obtained by adjusting the ratio of the protein adsorbed on the internal surface and the external surface. This suggests that the release pattern was determined by the adsorption state. One benefit is that the same carrier could have different release profiles making it possible to study the relationship between the release behavior and adjuvant effects without any distractions. Compared with free BSA alone, a significantly higher level of serum IgG, IgA induced by BSA/3DOM was observed and the release profile had an effect on the immunity. The IgG1 and IgG2a titers suggesting that both the Th1 and Th2 mediated immune response were induced. Therefore, this research could help in the development of a novel inorganic oral adjuvant and provide a new avenue for the administration of oral vaccine.
    Journal of Colloid and Interface Science 01/2014; 434:113–121. · 3.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purposes of this investigation are to design mesoporous carbon (MC) with spherical pore channels and incorporate CEL to it for changing its needlelike crystal form and improving its dissolution and bioavailability. A series of solid-state characterization methods, such as SEM, TEM, DSC and XRD, were employed to systematically investigate the existing status of celecoxib (CEL) within the pore channels of MC. The pore size, pore volume and surface area of samples were characterized by nitrogen physical absorption. Gastric mucosa irritation test was carried out to evaluate the safety of mesoporous carbon as a drug carrier. Dissolution tests and in vivo pharmacokinetic studies were conducted to confirm the improvement in drug dissolution kinetics and oral bioavailability. Uptake experiments were conducted to investigate the mechanism of the improved oral bioavailability. The results of solid state characterization showed that MC was prepared successfully and CEL was incorporated into the mesoporous channels of the MC. The crystallinity of CEL in MC was affected by different loading methods, which involve evaporation method and melting method. The dissolution rate of CEL from MC was found to be significantly higher than that of pure CEL, which attributed to reduced crystallinity of CEL. The gastric mucosa irritation test indicated that the MC caused no harm to the stomach and produced a protective effect on the gastric mucosa. Uptake experiments indicated that MC enhanced the amount of CEL absorbed by Caco-2 cells. Moreover, oral bioavailability of CEL loaded within the MC was approximately 1.59-fold greater than that of commercial CEL. In conclusion, MC was a safe carrier to load water insoluble drug by controlling the crystallinity or crystal form with improvement in drug dissolution kinetics and oral bioavailability.
    Materials Science and Engineering: C. 01/2014; 39:13–20.
  • [Show abstract] [Hide abstract]
    ABSTRACT: A new oral sustained drug delivery system (DDS) involving a combination of inorganic mesoporous material (CMK-5) and organic polymer poly dimethyl diallyl ammonium (PDDA) was established to determine its general suitability for use with poorly water soluble drugs. Nimodipine, Carvedilol and Fenofibrate, three different drugs with acidic or alkaline properties, were selected as model drugs and loaded into carriers. The physicochemical properties of the drug carriers were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nitrogen adsorption. The structural body changes of the composites in release medium, with or without additional salts, were also studied using particle sizing systems, nitrogen adsorption and zeta potential measurement in order to investigate the sustained release mechanism of the drugs. The results obtained showed that sustained release of drug from the designed DDS was mainly due to the blockage effect arising from the strong swelling of the coated polymers when in contact with release medium. Additional salts, when they reached a certain level, allowed a dramatic burst release. We believe that our designed sustained DDS provide a new option for water insoluble drugs and can be considered as fundamental for those more sophisticated DDS increasingly required in modern medical treatments.
    International Journal of Pharmaceutics 11/2013; · 3.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The goal of the present study was to compare the drug release properties and stability of the nanoporous silica with different pore architectures as a matrix for improved delivery of poorly soluble drugs. For this purpose, three dimensional ordered macroporous (3DOM) silica with 3D continuous and interconnected macropores of different sizes (200 nm and 500 nm) and classic mesoporous silica (ie, Mobil Composition of Matter [MCM]-41 and Santa Barbara Amorphous [SBA]-15) with well-ordered two dimensional (2D) cylindrical mesopores were successfully fabricated and then loaded with the model drug indomethacin (IMC) via the solvent deposition method. Scanning electron microscopy (SEM), N2 adsorption, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were applied to systematically characterize all IMC-loaded nanoporous silica formulations, evidencing the successful inclusion of IMC into nanopores, the reduced crystallinity, and finally accelerated dissolution of IMC. It was worth mentioning that, in comparison to 2D mesoporous silica, 3DOM silica displayed a more rapid release profile, which may be ascribed to the 3D interconnected pore networks and the highly accessible surface areas. The results obtained from the stability test indicated that the amorphous state of IMC entrapped in the 2D mesoporous silica (SBA-15 and MCM-41) has a better physical stability than in that of 3DOM silica. Moreover, the dissolution rate and stability of IMC loaded in 3DOM silica was closely related to the pore size of macroporous silica. The colorimetric 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Cell Counting Kit (CCK)-8 assays in combination with direct morphology observations demonstrated the good biocompatibility of nanoporous silica, especially for 3DOM silica and SBA-15. The present work encourages further study of the drug release properties and stability of drug entrapped in different pore architecture of silica in order to realize their potential in oral drug delivery.
    International Journal of Nanomedicine 01/2013; 8:4015-31. · 4.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Three different kinds of silica (S2, S1 and SBA-15) with different particle sizes (130, 430 nm and 1-2 μm) and different pore characteristics (i.e. pore size and shape) were developed as oral vaccine immunological adjuvants and the relationship between the silica architecture and immunological properties was investigated. The silica particles were characterized using SEM, TEM and nitrogen adsorption. Model antigen bovine serum albumin (BSA) was successfully entrapped into the silica pores to produce a sustained release vaccine delivery system. Compared with the responsiveness induced by parenteral administration of BSA emulsified in Freund's complete adjuvant (FCA), oral immunization with the silica/BSA formulation produced a stimulated humoral and mucosal (sIgA) response. The IgG and IgA titers induced by loading BSA was as follows: S1>S2>SBA-15. The highest IgG and IgA titers of S1 were attributed to its large honeycombed pores and the optimal particle diameter of 430 nm. The corresponding IgG1 and IgG2a titers were also investigated to confirm that BSA loaded in nanoparticles by oral immunization can induce both T-helper 1- and T-helper 2- (Th1 or Th2) mediated responses. We believe that the results of our research will open up new avenues for the formulation of oral vaccines.
    International Journal of Pharmaceutics 06/2012; 436(1-2):351-8. · 3.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The main aim of this study was to prepare nanosized hydroxycarbonate apatite (HCA) as a drug carrier to improve the dissolution rate and increase the bioavailability of poorly soluble drugs, intended to be administered orally. In the present study, uniform mesoporous HCA nanoparticles were synthesized using CaCO3 as a sacrificial template by the hydrothermal method in the presence of cetyltrimethylammonium bromide (CTAB) as a surfactant. The prepared HCA was used as a drug carrier to investigate the drug uptake and release properties employing carvedilol (CAR) as a model drug. The structure and morphology of mesoporous HCA, and the successful storage/release of CAR were systematically studied by N2 adsorption, scanning electron microscopy (SEM), powder X-Ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric (TG) analysis, Fourier transform infrared (FT-IR) spectroscopy, and UV–VIS spectrophotometry. In vitro drug dissolution tests showed that mesoporous HCA produced burst release of CAR in comparison with micronized CAR in simulated gastric fluid and intestinal fluid. Stability test result indicated that amorphous state of CAR loaded in HCA nanoparticles had a good physical stability after room storage for 6 months. Hence, mesoporous HCA nanoparticles are excellent drug carriers for the oral delivery of poorly soluble drugs.Highlights► Mesoporous hydroxycarbonate (HCA) was synthesized using CaCO3 as a template. ► Poorly water-soluble drug carvedilol was selected as a model drug. ► Carvedilol loaded in mesoporous HCA was in an amorphous state. ► Mesoporous HCA had high drug load efficiency and provided fast release of carvedilol. ► HCA is a good carrier for the oral delivery of poorly water-soluble drugs.
    Journal of Non-Crystalline Solids 01/2012; 358(2):229-235. · 1.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The present work was proposed not only to exploit the potential of 3D cage-like mesoporous silica SBA-16 with a well-defined spherical morphology as a carrier for poorly soluble drugs, but also to compare the drug loading and release properties of 3D cubic SBA-16 with that of classic 2D hexagonal MCM-41. SBA-16 microsphere with highly ordered mesostructures was synthesized by a facile method using block co-polymer F127 as template, cetyltrimethylammonium bromide (CTAB) as co-template and tetraethyl orthosilicate (TEOS) as silica source. Carvedilol (CAR), an antihypertensive agent, was used as a model drug and loaded into mesoporous silica via solvent deposition method at drug–silica ratio of 1:3. In vitro dissolution was performed in both simulated intestinal fluid (SIF, pH 6.8) and simulated gastric fluid (SGF, pH 1.2). Of particular interest was that in SIF both MCM-41 and SBA-16 samples exhibited promoted dissolution profile for CAR as compared to its corresponding crystalline form which exhibited poor dissolution behavior. This dissolution-enhancing effect might be due to the non-crystalline state and increased surface area of confined CAR as well as the hydrophilic nature of silica. In comparison with MCM-41, SBA-16 displayed a more rapid release profile in both SIF and SGF, which may be ascribed to the 3D interconnected pore networks and the highly accessible surface areas. The suitability of the utilization of SBA-16 microsphere as carriers will open new avenues for the formulation of poorly soluble drugs.
    Microporous and Mesoporous Materials 01/2012; 147(1):94–101. · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In order to improve the dissolution rate and increase the bioavailability of a poorly water-soluble drug, intended to be administered orally, the biocompatible and bioactive mesoporous hydroxyapatite (HA) was successfully synthesized. In the present study, mesoporous HA nanoparticles were produced using Pluronic block co-polymer F127 and cetyltrimethylammonium bromide (CTAB) as templates by the hydrothermal method. The obtained mesoporous HA was employed as a drug delivery carrier to investigate the drug storage/release properties using carvedilol (CAR) as a model drug. Characterizations of the raw CAR powder, mesoporous HA and CAR-loaded HA were carried out by the scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy, N2 adsorption/desorption, thermogravimetric analysis (TGA), and UV–VIS spectrophotometry. The results demonstrated that CAR was successfully incorporated into the mesoporous HA host. In vitro drug release studies showed that mesoporous HA had a high drug load efficiency and provided immediate release of CAR compared with micronized raw drug in simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.8). Consequently, mesoporous HA is a good candidate as a drug carrier for the oral delivery of poorly water-soluble drugs.Graphical abstractHighlights► Mesoporous hydroxyapatite was synthesized using F127 and CTAB as templates. ► Carvedilol was selected as a model drug. ► Carvedilol in an amorphous state was incorporated in mesoporous hydroxyapatite. ► Hydroxyapatite had a high drug load efficiency and provided fast release of carvedilol. ► Hydroxyapatite is a good carrier for the oral delivery of poorly water-soluble drugs.
    Applied Surface Science 01/2011; 257(23):10126-10133. · 2.54 Impact Factor