Zhi-Rong Zhang

Sichuan University, Hua-yang, Sichuan, China

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Publications (90)174.28 Total impact

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    ABSTRACT: The non-specific interaction between nanoparticles (NPs) and plasma proteins occurs immediately after NPs enter the blood, resulting in the formation of the protein corona that thereafter replaces the original NPs and becomes what the organs and cells really see. Consequently, the in vivo fate of NPs and the biological responses to the NPs are changed. This is one substantial reason for the two main problems of the NPs based drug delivery system, i.e. nanotoxicity and rapid clearance of NPs from the blood after intravenous injection. Here, we demonstrate the successful application of the preformed albumin corona in inhibiting the plasma proteins adsorption and decreasing the complement activation, and ultimately in prolonging the blood circulation time and reducing the toxicity of the polymeric PHBHHx NPs. Since the interaction of proteins with various nano-materials and/or -particles is ubiquitous, pre-forming albumin corona has a great potential to be a versatile strategy for optimizing the NPs based drug delivery system.
    Biomaterials 08/2013; · 8.31 Impact Factor
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    ABSTRACT: Aim:Breviscapine isolated from the Chinese herb Erigeron breviscapus (Vant) Hand.-Mazz is widely used to treat cardiovascular and cerebrovascular diseases. The aim of this study was to improve the pharmacokinetic profiles of breviscapine using nanostructured lipid carrier based on an ionic complex formation.Methods:Breviscapine nanostructured lipid carrier (Bre-NLC) was prepared using the thin film homogenization method. The morphology of Bre-NLCs was determined using transmission electron microscopy. The mean particle size, polydispersity index, zeta-potential analysis and entrapment efficiency were analized. In vitro release was studied using the dialysis method. In vitro stability was studied in fresh plasma and liver slurry of rats. In vivo pharmacokinetics was analyzed in rats after intravenous injection of a dose equivalent to breviscapine (10 mg/kg).Results:The Bre-NLCs were spherical with a mean particle size of ∼170 nm, a zeta potential of ∼20 mV and a high entrapment efficiency of ∼89%. Compared with a commercially available solution, a substantial decrease in the cumulative release of breviscapine was found for the Bre-NLCs. The NLC has a significantly protective effect against the liver enzyme degradation of breviscapine. After intravenous administration in rats, the Bre-NLCs exhibited a 32 times increase in the AUC0-t and a 12 times increase in T1/2 as compared to the commercially available breviscapine solution.Conclusion:The results demonstrate that the NLC has great potential to use as a novel sustained release system for breviscapine.
    Acta Pharmacologica Sinica 06/2013; · 2.35 Impact Factor
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    ABSTRACT: To prepare self-emulsifying delivery system (SEDDS) of Salvianolic acid B phospholipid complex (SalB-PC) and evaluate its quality. The best formulation was optimized using single-factor and pseudo-ternary phase diagrams, according to the emulsifying efficiency, the characteristics and partical size of the emulsion and other indicators. The morphology, particle size, zeta-potential and the release in artificial intestinal fluid of self-emulsifying formulation were evaluated. The weight ratio of SalB-PC: Lauroglycol FCC:Cremophor EL:Transcutol P in the best formulation was 9:45:40:15. SalB-PC loaded self-emulsifying formulation is yellow and transparent solution, with partical size about (187.2 +/- 7.1) nm, polydispersity index (PDI) about 0.267 +/- 0.008 and zeta-potential about (-35.6 +/- 2.7) mV after diluted about 100-fold. The self-emulsifying formulation released slower than the solution with only SalB or SalB-PC. Water-soluble drug Salvianolic acid B can be prepared to SEDDS, and this formulation can slow down the release of SalB in artificial intestinal fluid.
    Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 03/2013; 44(2):303-7.
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    ABSTRACT: PURPOSE: PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) is an excellent biomaterial for tissue repair. Here, we aim to develop a PHBHHx-based three-dimensional (3D) scaffold system for sustained delivery of proteins (insulin serves as a model protein). METHODS: The insulin-phospholipid complex (INS-PLC) was prepared to enhance the insulin lipophilicity. INS-PLC loaded PHBHHx 3D scaffolds (INS-PLC-SCAs) containing PEG-2000 were fabricated by lyophilization. In vitro release was performed in the medium with or without lipase. The bioactivity of INS-PLC-SCAs was measured in diabetic rats. RESULTS: In vitro release shows that the release rate of INS-PLC-SCAs was very slow (~6% of total insulin was released within 120 days), and PEG-2000 or lipase had no effect on its release pattern. The bioactivity test shows that the hypoglycaemic effect of insulin was maintained after formulated into scaffolds. After subcutaneous (s.c.) implantation, its therapeutic effect lasted for over 130 h, and its bioavailability was enhanced by 4-fold. CONCLUSIONS: PHBHHx based 3D scaffold has a great potential for sustained delivery of proteins, especially growth factors. When growth factors are incorporated, it can serve as a bifunctional system that provides a porous skeleton for cells attachment and proliferation, as well as a matrix for long term release of the loaded growth factors.
    Pharmaceutical Research 12/2012; · 4.74 Impact Factor
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    ABSTRACT: Aim: The purpose of this study was to develop a new orally delivered nanoparticulate system to improve the bioavailability of salmon calcitionin (sCT). Materials & methods: Four sCT-loaded solid lipid nanoparticles (SLNs) were prepared successfully by micelle-double emulsion technique via either the sole use of stearic acid (SA) or the combined use of SA and triglycerides (including tripalmitin [TP], trimyristin or trilaurin). Results: Compared with other SLNs, the combination of SA and TP could not only significantly improve the colloidal stability of SLNs and enhance the drug stability in the simulated intestinal fluids, but also intensively increase the intracellular uptake of drugs compared with the other SLNs (p < 0.05). The mechanism of internalization was an active transport involved in clathrin- and caveolae-dependent endocytosis. In vivo, the sCT SLNs prepared with SA and TP exhibited the highest reduction of plasma Ca(2+) level (17.44 ± 3.68%) with a bioavailability of 13.01 ± 3.24%. Conclusion: The SLNs formed by SA and TP as the solid lipids may be a promising carrier for oral delivery of peptide drugs. Original submitted 1 February 2012; Revised submitted 10 August 2012.
    Nanomedicine 10/2012; · 5.26 Impact Factor
  • Qian Geng, Xun Sun, Tao Gong, Zhi-Rong Zhang
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    ABSTRACT: Chronic kidney disease (CKD) is a worldwide public health problem, and unfortunately, the therapeutic index of clinically available drugs is limited. Thus, there is a great need to exploit effective treatment strategies, and the carrier-drug approach is an attractive method to improve the kidney specificity of the therapeutic agents. The aim of this present study is to develop a peptide-drug conjugate for the kidney targeted delivery of angiotensin-converting enzyme (ACE) inhibitor captopril (CAP), since G3-C12 peptide (ANTPCGPYTHDCPVKR) could specifically accumulate in the kidney after intravenous injection. Therefore, FITC labeled G3-C12 peptide (G3-C12-FITC) and peptide-drug conjugate (G3-C12-CAP) with a disulfide bond which can be cleaved by reduced glutathione in the kidney were prepared by solid-phase peptide synthesis. The fluorescence imaging of G3-C12-FITC revealed that the labeled peptide specifically accumulated in the kidney soon after i.v. injection to mice, and the accumulation is due largely to the reabsorption of the peptide by the proximal renal tubule cells. Furthermore, in comparison with the corresponding nonconjugated form, a 2.7-fold increase in renal area under concentration-time curve produced by the conjugate was observed in mice. Interestingly, the CAP entirely released in the kidney even at 0.05 h postinjection through disulfide reduction. As a consequence, the in vivo renal ACE inhibition was significantly increased. In conclusion, these findings suggest the potential of G3-C12 peptide serving as a suitable candidate carrier for kidney-targeted drug delivery.
    Bioconjugate Chemistry 06/2012; · 4.58 Impact Factor
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    Xuan Zhang, Xing Liu, Tao Gong, Xun Sun, Zhi-rong Zhang
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    ABSTRACT: Dexibuprofen, the S(+)-isomer of ibuprofen, is an effective therapeutic agent for the treatment of neurodegenerative disorders. However, its clinical use is hampered by a limited brain distribution. The aim of this study was to design and synthesize brain-targeting dexibuprofen prodrugs and to evaluate their brain-targeting efficiency using biodistribution and pharmacokinetic analysis. In vitro stability, biodistribution and pharmacokinetic studies were performed on male Sprague-Dawley rats. The concentrations of dexibuprofen in biosamples, including the plasma, brain, heart, liver, spleen, lung, and kidney, were measured using high pressure lipid chromatography (HPLC). The pharmacokinetic parameters of the drug in the plasma and tissues were calculated using obtained data and statistics. Five dexibuprofen prodrugs that were modified to contain ethanolamine-related structures were designed and synthesized. Their chemical structures were confirmed using (1)H NMR, (13)C NMR, IR, and HRMS. In the biodistribution study, 10 min after intravenous administration of dexibuprofen (11.70 mg/kg) and its prodrugs (the dose of each compound was equivalent to 11.70 mg/kg of dexibuprofen) in male Sprague-Dawley rats, the dexibuprofen concentrations in the brain and plasma were measured. The C(brain)/C(plasma) ratios of prodrugs 1, 2, 3, 4, and 5 were 17.0-, 15.7-, 7.88-, 9.31-, and 3.42-fold higher than that of dexibuprofen, respectively (P<0.01). Thus, each of the prodrugs exhibited a significantly enhanced brain distribution when compared with dexibuprofen. In the pharmacokinetic study, prodrug 1 exhibited a brain-targeting index of 11.19 {DTI=(AUC(brain)/AUC(plasma))(1)/(AUC(brain)/AUC(plasma))(dexibuprofen)}. The ethanolamine-related structures may play an important role in transport across the brain blood barrier.
    Acta Pharmacologica Sinica 02/2012; 33(2):279-88. · 2.35 Impact Factor
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    ABSTRACT: This study is to report the preparation of complexes of Ad5 and anionic liposomes (AL-Ad5), the amplification of adenoviruses with enhanced green fluorescent protein (eGFP) reporter gene performed by HEK 293 cells, the adenoviral vectors purified by cesium chloride gradient centrifugation, and the titer of adenovirus determined by cytopathic effect (CPE) method, hexon capsid immunoassay and quantitative-PCR (Q-PCR), separately. The prescription and experiment conditions were optimized by central composite design (CCD). The complexes of Ad5 and AL-Ad5 were formulated by the calcium-induced phase change method. The morpholopy, particle size and zeta potential were detected by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. Additionally, the bicolourable fluoresce-labeled complexes (F(labeled)-AL-Ad5) were prepared and their intracellular location in MDCK cells was detected by confocal laser scanning microscopy (CLSM). The results indicate that the complexes of AL-Ad5 exhibited a uniform distribution with a particle size of 211 +/- 10 nm and a zeta potential of -41.2 +/- 2.2 mV. The result of CLSM demonstrates that the intracellular location of red fluoresce-labeled adenovirus was consistent with that of green fluoresce-labeled liposomes suggesting that the naked adenovirus was well encapsulated by the anionic liposomes in complexes of AL-Ad5.
    Yao xue xue bao = Acta pharmaceutica Sinica 01/2012; 47(1):116-23.
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    ABSTRACT: Galectin-3 (Gal-3), over-expressed on a variety of human tumor cells, is a potential binding site for targeted metastatic prostate cancer therapy. The aim of this study was to develop a G3-C12-mediated drug delivery system based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers targeting to Gal-3-expressed human PC-3 prostate carcinoma cells. 5-Fluorouracil (5-Fu), an anti-tumor agent, was selected as a model drug. G3-C12, a binding peptide, which specifically binds to the carbohydrate-recognition domain (CRD) of Gal-3, was attached to HPMA copolymers as a targeting moiety. Compared with non-targeted conjugates (P-Fu), Gal-3-targeted HPMA copolymer-(G3-C12)-5-Fu conjugates (P-(G3-C12)-Fu) displayed a superior intracellular internalization followed by enhanced cytotoxicity and apoptosis-induction. Subsequently, the in vitro migration study on PC-3 cells indicated that P-(G3-C12)-Fu was able to efficiently inhibit the cell migration ability after wounding. On PC-3 tumor-bearing mice model, G3-C12-modified copolymers showed a higher tumor accumulation coupled with a faster clearance from blood circulation than non-modified ones. Finally, Gal-3-targeted conjugates significantly improved the anti-tumor activity of 5-Fu in nude mice bearing PC-3 tumor xenografts. Consequently, G3-C12 would be a promising targeting moiety for cell-specific prostate cancer therapy in future.
    Biomaterials 12/2011; 33(7):2260-71. · 8.31 Impact Factor
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    ABSTRACT: The application of poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) for sustained and controlled delivery of hydrophilic insulin was made possible by preparing insulin phospholipid complex loaded biodegradable PHBHHx nanoparticles (INS-PLC-NPs). The INS-PLC-NPs produced by a solvent evaporation method showed a spherical shape with a mean particle size, zeta potential and entrapment efficiency of 186.2 nm, -38.4 mv and 89.73%, respectively. In vitro studies demonstrated that only 20% of insulin was released within 31 days with a burst release of 5.42% in the first 8 h. The hypoglycaemic effect in STZ induced diabetic rats lasted for more than 3 days after the subcutaneous injection of INS-PLC-NPs, which significantly prolonged the therapeutic effect compared with the administration of insulin solution. The pharmacological bioavailability (PA) of INS-PLC-NPs relative to insulin solution was over 350%, indicating that the bioavailability of insulin was significantly enhanced by INS-PLC-NPs. Therefore, the INS-PLC-NPs system is promising to serve as a long lasting insulin release formulation, by which the patient compliance can be enhanced significantly. This study also showed that phospholipid complex loaded biodegradable nanoparticles (PLC-NPs) have a great potential to be used as a sustained delivery system for hydrophilic proteins to be encapsulated in hydrophobic polymers.
    Biomaterials 11/2011; 33(5):1583-8. · 8.31 Impact Factor
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    ABSTRACT: Aerosol glucocorticoid medications have become more and more important in treating BA (bronchial asthma). Although these agents are dosed to directly target airway inflammation, adrenocortical suppression and other systematic effects are still seen. To tackle this problem in a novel way, two L-carnitine ester derivatives of prednisolone (as the model drug), namely, PDC and PDSC, were synthesized to increase the absorption of prednisolone across the human bronchial epithelial BEAS-2B cells by the organic cation/carnitine transporter OCTN2 (SLC22A5) and then to slowly and intracellularly release prednisolone. The transport of prednisolone, PDC and PDSC into the human bronchial epithelial BEAS-2B cells was in the order PDSC > prednisolone > PDC at 37 °C. It was found that PDSC displayed 1.79-fold increase of uptake compared to prednisolone. Transport of PDSC by BEAS-2B was temperature-, time-, and Na(+)-dependent and saturable, with an apparent K(m) value of 329.74 μM, suggesting the involvement of carrier-mediated uptake. An RT-PCR study showed that organic cation/carnitine transporters OCTN1 and OCTN2 are expressed in BEAS-2B cells, but little in HEK293T cells. The order of uptake by HEK293T was prednisolone > PDC > PDSC. In addition, the inhibitory effects of organic cations such as L-carnitine, ergothioneine, TEA(+) and ipratropium on PDSC uptake in BEAS-2B cells were in the order L-carnitine > ipratropium > TEA(+) > ergothioneine, whereas their inhibitory effects on PDSC uptake in HEK293T cells were negligible. Finally, in vitro LPS-induced IL-6 production from BEAS-2B was more and longer suppressed by PDSC than prednisolone and PDC. All of these results suggested PDSC may be an attractive candidate for asthma treatment.
    Molecular Pharmaceutics 08/2011; 8(5):1629-40. · 4.57 Impact Factor
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    ABSTRACT: To investigate the influence of N-acetylation of chitosan on the renal targeting. Hydroxyethyl chitosans (HECs) with different N-acetylation degrees of 10.0%, 52.7%, and 81.8% (HECs-10, HECs-53, and HECs-82) were synthesized. Then, in vitro evaluations including cellular uptake and cytotoxicity were performed. Finally, tissue distribution of HECs in normal mice and megalin-shedding mice models were evaluated. HECs-10 exhibited the highest binding affinity and uptake capacity to MDCK cells, expressing the megalin receptor. Additionally, cytotoxicity assay showed that there were no obvious effects of HECs on the viability of L929 and MDCK cells. Consistent with the cellular uptake study, it was shown in vivo study that all HECs exhibited renal-targeting profile. Especially, HECs-10 with low N-acetylation overwhelmingly accumulated in the kidneys, while urinary excretion of HECs-10 was low, in comparison with that of HECs-53 and HECs-82. Finally, the renal accumulation of HECs in megalin-shedding mice was dramatically reduced by over ~50% as compared with that in normal animals and the specific renal uptake of HECs was increasingly inhibited with the N-acetylation increased. Inspired by these observations, we can conclude that decreasing the N-acetylation could enhance accumulation of low-molecular-weight chitosan in kidneys and amino groups in the structure could be essential for renal-targeting profile of chitosan.
    Journal of Drug Targeting 08/2011; 19(7):540-51. · 2.77 Impact Factor
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    ABSTRACT: Owing to the quick elimination of drug from duodenum and the depth of Helicobacter pylori (H. pylori) colonized in mucus, antibiotic therapy often fails in the eradication of H. pylori infection for duodenal ulcer. A novel duodenum-specific microsphere (DSM) consisting of three-layer structure was developed to enhance the drug concentration and retention time in duodenal mucus layer. Firstly a core-shell mucoadhesive microsphere was prepared with a novel emulsification/coagulation coating method by introducing drug loaded Eudragit cores into a thiolated chitosan mucoadhesive layer. Then the obtained core-shell mucoadhesive microspheres were further coated with hydroxypropyl methylcellulose acetate maleate as the pH-sensitive layer for the trigger of mucoadhesion and drug release in duodenum. From the fluorescence microscopic and scanning electron microscopic images, the three-layer structure was successfully established. The microspheres exhibited a duodenum-specific trigger performance, good mucoadhesive property and pH-dependent drug release. In vivo study performed in rats demonstrated that DSM exhibited about 3-fold augmentation of AUC and about 5-fold augmentation of C(max) for duodenal mucus drug concentration compared with free drug suspension. These results suggest that the three-layer structure microspheres may provide a promising approach for duodenum-targeting drug delivery system.
    International Journal of Pharmaceutics 07/2011; 413(1-2):110-8. · 3.99 Impact Factor
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    ABSTRACT: Literature has highlighted the practical use of solid lipid nanoparticles (SLNs) in research, but few reports have combined SLNs with miRNA-based therapy. We aimed to prepare SLNs to load anti-miRNA oligonucleotide (AMO) for miRNA-based therapy in vitro. SLNs were employed to encapsulate AMO by a solvent diffusion method, and then the properties of AMO-CLOSs (cationic lipid binded oligonucleotide (AMO)-loaded SLNs) were characterized. We studied cellular uptake and activation properties of AMO-CLOSs in A549 cells, including antisense efficiency, cell migration and invasion. AMO-CLOSs were 187 nm in size and 46.6 mV in zeta potential with an approximately toroid morphology in the TEM image. AMO-CLOSs uptake by A549 cells was increased significantly higher and more effective than free AMO. Further results demonstrated that AMO-CLOSs showed high antisense efficiency of microRNA-21 and subsequently decreased the proliferation, migration and invasion of tumor cells. These findings suggest that AMO-CLOSs represent a potential new approach for carrying anti-miRNA inhibitors for cancer therapy.
    Pharmaceutical Research 07/2011; 29(1):97-109. · 4.74 Impact Factor
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    ABSTRACT: The aim of the present study was to investigate the effects of varying degrees of quaternization (DQ: 22, 35 and 41%) on the preparation and characterization of insulin (INS)-loaded polyelectrolyte complexes (PECs) prepared by N-trimethyl chitosan chloride (TMC). A two factor-five level central composite design was used for the optimization. The concentrations of INS and TMC were defined as independent variables, while the entrapment efficiency (EE%) and loading efficiency (LE%) as dependent variables. The three optimized INS-TMC PECs were characterized for their size, zeta potential, EE% and LE%. The morphology and electrostatic interaction of PECs were evaluated. Then, the stability in the enzyme solution and in vitro release as well as mucoadhesive properties of the three PECs were all investigated. The results showed that the size and EE% of the optimum formulations were significantly decreased using TMC of higher DQ, while the zeta potential and LE% were slightly influenced by DQ. The stability assay exhibited partial protection of TMC PECs, and the better protective effect was observed for PECs of higher DQ. The in vitro release study presented different initial and sustained release behaviors of INS-TMC PECs and the mucin adsorption study confirmed a positive correlation between the DQ and the mucoadhesive property of PECs.
    Pharmaceutical Development and Technology 05/2011; · 1.33 Impact Factor
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    ABSTRACT: A series of curcumin analogues with different substituents at the 4-position of the phenyl group were synthesized and screened for in vitro cytotoxicity against a panel of human cancer cell lines. Several novel curcumin analogues, especially 32 and 34, exhibited selective and potent cytotoxic activity against human epidermoid carcinoma cell line A-431 and human glioblastoma cell line U-251, implying their specific potential in the chemoprevention and chemotherapy of skin cancer and glioma. The preliminary SAR information extracted from the results suggested that introduction of appropriate substituents to the 4'-positions could be a promising approach for the development of new cytotoxic curcumin analogues with special selectivity for A-431 and U-251 cell lines.
    Bioorganic & medicinal chemistry letters 02/2011; 21(3):1010-4. · 2.65 Impact Factor
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    ABSTRACT: Particulate systems that could deliver drug specifically to duodenum have not yet been reported. The aim of this study was to develop a novel duodenum-specific drug delivery system based on thiolated chitosan and hydroxypropyl methylcellulose acetate maleate (HPMCAM) for the duodenal ulcer application. Berberine hydrochloride was used as model drug. Thiolated chitosan was synthesized and further used for the preparation of mucoadhesive microspheres. HPMCAM, which is insoluble below pH 3.0 was synthesized and used for the coating of thiolated chitosan microspheres (TCM). The resulting thiolated chitosan immobilized on chitosan was 268.21 ± 18 μmol/g. In vitro mucoadhesion study showed that the mucoadhesion property of TCM was better than that of chitosan microspheres. Morphological observation showed that the HPMCAM coating would maintain its integrity in simulated gastric fluid (SGF) for 2 h and dissolved quickly in simulated pathological duodenal fluid (SPDF; pH 3.3). In vitro drug release studies showed that only 4.75% of the drug was released in SGF for 2 h, while nearly 90% of the drug was released within 6 h after transferring into SPDF.
    Drug Development and Industrial Pharmacy 01/2011; 37(7):868-74. · 1.54 Impact Factor
  • Yu Nie, Zhi-Rong Zhang, Bin He, Zhongwei Gu
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    ABSTRACT: Nanoparticles were formulated with biodegradable monomethoxy (poly ethylene glycol)-poly(lactide-co-glycolide)-monomethoxy (poly ethylene glycol) of three different proportional (PEG-PLGA-PEG, lactic acid: glycolic acid = 80/20, 70/30, 50/50) and the cytotoxicity of nanoparticle was characterized according to US Pharmacopoeia XXIII recommendations on various cell lines, including L929, Chang's hepatocytes, primary mouse myoblasts, osteoblasts, and renal vascular endothelial cells. mIL-18 gene was first condensed by polycationic peptide polylysine (PLL), and then encapsulated in the PEG-PLGA-PEG NPs as a novel multi-polyplex gene delivery system - Polymer-PLL-DNA. (PPDs) After lyopholization, the morphology, particle size, zeta potential, and the integrity of DNA in the NPs were investigated. The expression of mIL-18 gene on CT-26 cells in vitro were determined by western blot, while in vivo efficacy was evaluated by tumor inhibition rate, histological section, and survival curve in pulmonary metastasis of colon cancer in BALB/c mice model. Results showed that the cytotoxicity of blank nanoparticles was related to the degradation properties of the polymers with different compositions. The NPs with LA:GA = 70/30 (NPs-73) was optimal for intravenous injection due to its low cytotoxicity. Physicochemical properties of the PPDs were not changed during the lyopholization, while mIL-18 was successfully expressed in vitro. The anti-tumor efficacy in vivo of PPDs showed improvement especially combined with chemotherapy of cisplatin, and confirmed the promising application of the PPDs system, which compared with any single treatment.
    Journal of Biomaterials Applications 01/2011; 26(8):893-916. · 2.64 Impact Factor
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    Rui-ling Duan, Xun Sun, Jie Liu, Tao Gong, Zhi-rong Zhang
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    ABSTRACT: To prepare a novel formulation of phosphatidylcholine (PC)-bile salts (BS)-mixed micelles (MMs) loaded with silybin (SLB)-PC complex for parenteral applications. SLB-PC-BS-MMs were prepared using the co-precipitation method. Differential scanning calorimetry (DSC) analysis was used to confirm the formation of the complex and several parameters were optimized to obtain a high quality formulation. The water-solubility, drug loading, particle size, zeta potential, morphology and in vivo properties of the SLB-PC-BS-MMs were determined. The solubility of SLB in water was increased from 40.83 ± 1.18 μg/mL to 10.14 ± 0.36 mg/mL with a high drug loading (DL) of 14.43% ± 0.44% under optimized conditions. The SLB-PC-BS-MMs were observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and showed spherical shapes. The particle size and zeta potential, as measured by photon correlation spectroscopy (PCS), were about 30 ± 4.8 nm and -39 ± 5.0 mV, respectively. In vivo studies showed that incorporation of the SLB-PC complex into PC-BS-MMs led to a prolonged circulation time of the drug.Conclusion:This novel formulation appears to be a good candidate for drug substances that exhibit poor solubility for parenteral administration.
    Acta Pharmacologica Sinica 01/2011; 32(1):108-15. · 2.35 Impact Factor
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    ABSTRACT: Microparticles containing solid lipid nanoparticles (SLNs) are receiving increased attention as carriers for the lung delivery of the SLNs. Thus, we aim to prepare the hybrid microparticles and thoroughly evaluate their feasibility for the pulmonary drug delivery. The microparticles were prepared by co-spray-drying the thymopentin (TP5)-loaded SLNs with bulking agents. Thereafter, we systematically estimated the potential of the microparticles as the carriers for the pulmonary delivery of the SLNs, including the investigations of their characteristics, aerodynamic properties, pharmacokinetics and pharmacodynamics. The spherical and hollow microparticles presented a size of 4.1 +/- 0.1 microm and a low tap density of 0.175 +/- 0.02 g/cm(3). In addition, the microparticles showed a high aerosolization efficiency (emitted dose of 98.0% +/- 1.23% and respirable fraction of 51.07% +/- 1.21%). Furthermore, the SLNs could be easily recovered from the microparticles without essential changes on their characteristics and the drug release behavior. The pharmacokinetic and pharmacodynamic studies suggested that, compared to i.v. TP5 solution, the bioavailability and therapeutic efficacy of TP5 were remarkably strengthened after the pulmonary administration of the microparticles. Taken together, we believe the microparticles were suitable for inhalation and possessed an ample potential for the pulmonary delivery of the SLNs.
    Pharmaceutical Research 09/2010; 27(9):1977-86. · 4.74 Impact Factor

Publication Stats

460 Citations
174.28 Total Impact Points

Institutions

  • 2002–2013
    • Sichuan University
      • • Key Laboratory of Drug Targeting and Novel Drug Delivery System
      • • Department of Pharmaceutics
      • • West China School of Pharmacy
      Hua-yang, Sichuan, China
  • 2009
    • Southwest University for Nationalities
      Hua-yang, Sichuan, China
  • 2005
    • Shandong University
      Chi-nan-shih, Shandong Sheng, China