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Study on microemulsion with mixing oils to improve ibuprofen bioavailability

Study on microemulsion with mixing oils to improve ibuprofen...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： You Xiuhua,Li Yuan,Hu Haiyan~* School of Pharmaceutical Sciences,Sun Yat-sen University.

Objective:A big amount of surfactants were in need to form microemulsions and consequent toxicity restricted the application of *** decrease the amount of surfactants in microemulsion is *** present research showed that mixing oils could enlarge the domain of microemulsions and reduce the amount of *** it is unknown whether lower amount of surfactants in microemulsions induce lower bioavailability or *** purpose of this research is to study the factors influencing the domain of mixing oils microemulsions and confirm whether lowing amount of surfactants in microemulsions induce lower bioavailability or not. Methods:***(IBU),drug of BCSⅡ,was used as the model *** IBU loaded microemulsion formulations were optimized using a pseudotemary ternary phase diagram by comparing the percentage of microemulsion area(MA)and percentage of microemulsion area solubilied by 30%stot(MAS30).Appearance and morphology,droplet size,zeta potential and stabilities of the optimized IBU microemultions were characterized and evaluated. *** ratios of the mixing oils,amount of double bond in oils,carbochain length of oil,and types of cosurfactant had been investigated to explain the effectiveness of mixing oils. *** LC-MS/MS method was developed to quantitative determination of IBU in rat *** with IBU suspension,the pharmacokinetics of IBU loaded microemulsions composed single oil and mixing oils in rats were investigated. Result:*** formations was obtained composed Tween80-CremopherEL-PEG(1:1:2)as the Stot and GTCC-Maisine?35-1 (1:1)as the mixing *** microemulsions containing 1%IBU were prepared in which the percentages of oils are 6%(single oil),6%(mixing oils),and 15%(mixing oils)and surfantances are 24%,24%and 16%.The droplet size distribution was found to be 20～40 *** microemulsions were stable when diluted and centrifugated. 2 The most effective mixing ration of GTCC to Maisine?35-1 was 1:*** MAS30 w

关键词： microemulsion mixing oils bioavailability ibuprofen

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Synthesis and properties of amylose modified as inclusion function and pH-sensitivity drug carrier

Synthesis and properties of amylose modified as inclusion fu...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Qifang WANG,Hongzhuo LIU,Xiaowen FAN,Xin CHE,Sanming LI~* College of Pharmacy,Shenyang Pharmaceutical University,Wenhua Road 103,Shenyang,110016,China

Objective:This study was to prepare a novel copolymer with a molecular inclusion component such as helical amylase and a pH-sensitive component such as acrylic acid（AAc）*** copolymer obtained may not only possess the function of drug inclusion,but may also sensitively respond to environmental pH ***:firstly,a reactive helical amylose（AM）based monomer carrying vinyl carylboxic acid functional groups was synthesized by reaction of AM with maleic anhydride（MAH）.Then, through graft copolymerization of the monomer with acrylic acid（AAc）,a novel copolymer,poly（AM-g-AAc）possessing molecular inclusion function plus pH-sensitivity characters,was prepared by free radical polymerization using a redox system as the initiator. The structure and properties were characterized by FT-IR and elemental *** pH-sensitivity character was tested in both the simulated gastric and intestinal pH ***:The FT-IR results evidences that the AAc were conjugated with AM-MAH backbones through ester *** elemental analysis was C:46.3%,H:5.1%in the AM-MAH,therefore,the composition of AM-MAH monomer was considered to be CHO[COCH=CHCOOH],which a helix unit in the amylose carrying five vinyl carboxylic acid *** swelling studies showed that increasing pH from 1.2 to 7.4,a considerable increase in swelling ratio was observed for the poly（AM-g-AAc）,indicating the copolymer synthesized possess pH sensitive *** the reason,with the increase of pH,-COOH group of the copolymer begins to be ionized,the ionized-COOcould regain relatively good hydrophilicity due to the electrostatic repulsive force and increasing the osmotic pressure inside the polymer,leading to the polymer expanding,and cause the swelling reaching a relatively lager value *** used the copolymer as drug carrier,a possible mechanism of drug release was shown in ***:The drug release profile from the poly（AM-g-AAc）might be better controlled due to the improved inte

关键词： Amylose copolymer molecular inclusion pH-sensitive Drug carrier

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Intra-articular drug delivery from a topical patch containing teriflunomide and lornoxicam for rheumatoid arthritis treatment:Does the topical patch really enhance a local treatment?

Intra-articular drug delivery from a topical patch containin...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Honelei Xi~(a,+),Dongmei Cun~a,Rongwu Xiang~b,Yanli Guan~a,Yuxiu Zhang~a,Yuanru Li~a,Liang Fang~(a,++) a Department of Pharmaceutical Sciences,Shenyang Pharmaceutical University,Shenyang 110016,China b School of medical instrument,Shenyang Pharmaceutical University,Shenyang 110016,China.

Purpose:The aim of this work is to investigate intra-articular delivery of teriflunomide(TEF)and lornoxicam(LOX)following transdermal patches applied topically and whether the topical patches really enhance a local treatment for rheumatoid arthritis(RA). Method:After topical application of a compound patch containing TEF and LOX to only one knee joint in rabbit,intra-articular delivery of TEF and LOX on the application site was compared with that on the non-application ***-inflammatory effects on primary arthritis of bilateral hind paws were evaluated in the RA model,following the compound patches on only one knee of rats at 5 day after the injection of complete Freund's adjuvant in bilateral hind paws. Results:The results(Fig.1)showed that TEF and LOX were transferred into skin,ligament and fat pad on the application site by direct diffusion and on the non-application site by the redistribution of systemic blood supply,while local absorption of TEF and LOX in synovial fluid originated from the systemic blood ***,she compound patches displayed an outstanding response on bilateral joint inflammations and there was no significant difference between the swelling alterations of bilateral hind paws in all the groups(Fig.2).Although LOX played a leading role for anti-inflammatory,TEF in the compound patches could not ignored its effect on controlling the RA activity. Conclusion:Based on the above result,although transdermal administration applied topically can provide a local enhanced drug delivery for the superficial joint tissues by direct diffusion,it seems unlikely to do that for the deeper tissue synovial fluid.

关键词： teriflunomide lomoxicam topical patch intra-articular drug delivery

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Novel sustained and controlled insulin release systems based on a biodegradable and biocompatible polyester Poly-3-hydroxybutyrate-co-3-hydroxyhexanoate(PHBHHx)

Novel sustained and controlled insulin release systems based...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Qiang Peng,Tao Gong,Xun Sun,Zhirong Zhang~* Key Laboratory of Drug Targeting and Drug Delivery Systems,Ministry of Education,West China School of Pharmacy,Sichuan University,Chengdu,People's Republic of China

Diabetes,the source of many deadly diseases,has been considered as the most dangerous epidemics in the *** therapeutic approaches are varied according to different type of *** insulin therapy is always an important treatment method for both types of *** administration is an ideal route but limited by the intrinsic instability of ***,subcutaneous(sc) injection is still the main route for insulin ***,however,the diabetic patients have to receive injections for as lease once a day,which brings lots of troubles and pains and leads to a very low patient ***,the objective of this project is to develop novel sustained and controlled insulin release systems by use of a biodegradable and biocompatible polyester, and thus to reduce the injection frequency significantly and enhance the patient compliance. Poly-hydroxybutyrate-co-hydroxyhexanoate(PHBHHx),one of the members of the microbial polyhydroxyalkanoates(PHA) biopolyester family,is now commercially available and has been widely used as a scaffold material in tissue engineering due to its adjustable mechanical properties,biodegradability,biocompatibility and ***,its application in sustained and controlled drug release is still a blank ***,this present work is going to investigate its potential serving as a sustained and controlled drug delivery carrier using insulin as a model *** work is divided into three parts,including PHBHHx nanoparticles system,PHBHHx nanoparticles loaded chitosan thermosensitive hydrogels,and PHBHHx 3D scaffolds. In the first part,insulin phospholipid complex(INS-PLC)is prepared to improve the lipophilicity of insulin and its affinity to the lipophilic material ***-PLC loaded PHBHHx nanopartices(INS-PLC-NPs)are prepared using solvent evaporation method and characterized in vitro and in *** size,polydisperse index(PDI),zeta potential,and entrapment efficiency of INS-PLC-NPs a

关键词： diabetes insulin poly-hydroxybutyrate-co-hydroxyhexanoate(PHBHHx) controlled release

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The study on paclitaxel loaded lipid nanoparticles to reverse tumor resistance

The study on paclitaxel loaded lipid nanoparticles to revers...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者：李云龙游剑杜永忠袁弘胡富强虞和永浙江大学药学院

Introduction Paclitaxel(PTX)is one of the most effective and most widely-used anti-cancer ***,there is almost more than 90%death of the patients associated with drug *** is not easy to formulate for parenteral administration because of its low aqueous *** EL,the excipient used for its formulation to increase the solubility of PTX,has been shown to cause serious side effects.[1]Our work was to design a new PTX nanoparticle delivery system with the ability of reversing tumor resistant,based on the *** delivery system(DDS)is a novel approach to overcome multidrug resistance(MDR)in *** study aimed at if the DDS have the ability of concentrating at tumor site or reversing tumor *** model cell line are the human ovarian tumor cell(SKOV-3),human breast tumor cell line(MCF-7)and the corresponding resistance cell line(ST-30),(MCF-7/ADR). Experiment The PTX-loaded nanoparticle was prepared by microfluidization ***,The physico-chemical properties of the nano-emulsion were characterized,including size,drug loading coefficient,in vitro release *** cytotoxicity of the PTX-loaded nano-emulsion was assessed against SKOV-3,ST-30,MCF-7 and MCF-7/ADR,by a standard 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl(MTT)assay,*** order to understand the tumor targeting of the drug delivery, the distribution in vivo was carried out. Results and Conclusion The results showed that the nano-emulsion size was less than 200nm in the Z-average,which has relationship with the drug *** cytotoxity of the MCF-7 and MCF-7/ADR cell line were 1.3 g/ml and 5.1 g/ml, ***'s more,the results of distribution in vivo demonstrated that the drug delivery system can concentrate in tumor with the time goes *** results indicated that PTX nanoparticle can target tumor site and reverse the drug resistance,which means that the PTX nanoparticle is proper drug delivery system.

关键词： Paclitaxel nanoparticle reverse resistance

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Targeting and Hyperthermia of doxorubicin by the Delivery of Single Walled Carbon Nanotubes to EC-109

Targeting and Hyperthermia of doxorubicin by the Delivery of...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Huijuan Zhang,Zhenzhong Zhang~* School of Pharmaceutical Sciences,Zhengzhou University,100 Kexue Avenue,Zhengzhou 450001,Henan,P.R.China

Aim:To introduce AS1411(this aptamer targets nucleolin on the cell surface)to complex between ADM and SWNT to enhance targeted delivery of ADM,and to use 808 nm NIR laser for photothermal treatment to achieve the effect of targeting, controlled release and ***:Water-soluble SWNTs were made by oxidizing and functionalizing with poloxamer ***-AS1411-SWNTs tertiary complex formation was formed according physical adsorption and electrostatic *** was analyzed by TEM,infrared spectrophotometry,differential scanning calorimeter,particle size and potential *** release profiles from the complex were investigated in pH7.4 and *** cytotoxic studies,EC-109 cells were treated with ADM,AS1411, ADM-AS1411,ADM-AS *** was combined with the complex to evaluate the uptake of EC-109 in vitro analyzed. Cell cycle was analyzed by flow ***:The concentration of SWNTs in water reached 2.0g/*** was efficiently loaded onto SWNTs(efficiency 121%).The best ratio for combination of AS1411 and SWNTs-ADM was 2:*** particle size and potential of the tertiary complex were 109.5±1.0nm and +4.45±*** was released from the tertiary complex in a pH-dependent manner(higher release rate at pH5.5).Internalization analysis showed that the tertiary complex may transfer into the cell through the membrane in two ***-AS 1411-SWNTs was more cytotoxic in EC-109 cells compared to ADM alone. SWNTs was proved to have strong hot therapeutical effect and the ability was concentration and time dependent.A synergistic effect was observed in EC-109 cell line treated with AS 1411 in combination with doxorubicin increasing potency by 2-fold(72h).The G2 / M phase cells was significantly increased(increased from 56.8%(ADM)to 76.5%(ADM-AS1411-SWNTs)and 95.7% (hyperthermia of complex).Conclusion:This system had the effect of targeting,controlled release and *** was a synergistic effect in EC-109 cell lines treated with AS 141

关键词： SWNTs ADM AS1411 pH-dependant hyperthermia synergy

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A biomimetic nanovector-mediated targeted cholesterol-conjugated siRNA delivery for tumor gene therapy

A biomimetic nanovector-mediated targeted cholesterol-conjug...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Wei Wang.Yang Ding,Jianping Zhou~* State Key Laboratory of Natural Medicines,Department of Pharmaceutics,China Pharmaceutical University,24 Tongjiaxiang, Nanjing 210009,China

The study aimed to develop a biomimetic nanovector,reconstituted high density lipoprotein(rHDL),mediating targeted cholesterol-conjugated siRNA(Chol-siRNA)delivery for Pokemon gene silencing ***-siRNA-loaded rHDL nanoparticles (rHDL/Chol-siRNA complexes)were prepared using thin-film dispersion method and their characteristics were investigated in detail. RHDL/Chol-siRNA complexes at the optimal volume ratio(lipid:Chol-siRNA)exhibited high Chol-siRNA-loading efficiency (-99%),desirable nanoparticle size and excellent stability in *** addition,by analyzing Chol-siRNA release profile, rHDL/Chol-siRNA complexes displayed sustained release and storage stability *** from FACS and confocal microscopic analyses revealed that rHDL-mediated carboxyfluorescein tagged Chol-siRNA(FAM-Chol-siRNA)transfection resulted in highly efficient uptake and specific cytoplasmic delivery of FAM-Chol-siRNA into human hepatocellular carcinoma cell line HepG2 via HDL-receptor mediated *** vitro cytotoxicity,apoptosis and necrosis studies and Western-blot analysis revealed significant cellular growth inhibition and decrease of Pokemon and Bcl-2 protein expression in HepG2 cells treated with Chol-siRNA-Pokemon-loaded rHDL nanoparticles(rHDL/Chol-siRNA-Pokemon complexes),*** in vivo studies,the near-infrared(NIR)dye Cy5 labeled Chol-siRNA-loaded rHDL nanoparticles(rHDL/Cy5-Chol-siRNA complexes)obviously accumulated in tumor of nude mice after *** as compared with Cy5-Chol-siRNA-loaded lipoplexes (Lipos/Cy5-Chol-siRNA complexes).Moreover,rHDL/Chol-siRNA-Pokemon complexes demonstrated great tumor growth inhibition and significant decrease of Pokemon and Bcl-2 protein expression in *** results suggested that rHDL should be an ideal non-viral tumor-targeting vector for Chol-siRNA transfer,and rHDL-mediated Chol-siRNA-Pokemon delivery might be a promising new strategy for gene therapy in hepatocellular carcinoma.

关键词： Reconstituted high density lipoprotein Apolipoprotein A-I Targeted cholesterol-conjugated siRNA delivery Pokemon Tumor gene therapy

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Bone marrow-derived mesenchymal stem cells expressing HSV/TK via a non-viral vector for targeted cancer gene therapy

Bone marrow-derived mesenchymal stem cells expressing HSV/TK...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Tian-Yuan Zhang,Yu-Lan Hu,Jian-Oing Gao Department of Pharmaceutics,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou,China

Aim:The aim of his study was to investigate the possibility to use the bone marrow-derived mesenchymal stem cells(BMSCs)as a pulmonary targeting gene micro/nano-vector in the therapy for anti-metastatic lung cancer combined with ganciclovir/herpes simplex virus thymidine kinase(GCV/HSV-tk)prodrug anti-tumor system. Methods:The novel non-viral vector was synthesized through chemically introduced spermine to the hydroxyl groups of pullulan by an N,N'-carbonyldiimidazole(CDI)activation *** effect of BMSCs transfected with tk(BMSCs-tk)/GCV in vitro was detected using the MTT *** pulmonary migration of BMSCs was evaluated by in vivo bioluminescence imaging system after systemic injection of the CM-Dil stained BMSCs into B16F10 lung metastasis tumor load C57BL6 *** therapeutic effect of BMSCs-tk on tumor growth in vivo was conducted by intravenous injection transfected BMSCs into lung metastasis model mouse followed with GCV(50mg/kg in PBS)intraperitoneal *** colonies on lung surface were counted to evaluate the anti-tumor effect. Results:Elementary analysis showed spermine-pullulan was successfully synthesized,and the molar extent of spermine introduced to the hydroxyl groups of pullulan was 13.99 mole%.This novel gene vector demonstrated relative high transfection efficiency and low cytotoxic compared with PEL Suicide effect tests presented that BMSCs which transfected with HSV-tk via spermine-pullulan can significantly inhibit its proliferation at the presence of GCV,while the un-transfected BMSCs had no effect on cell proliferation in the same *** vivo bioluminescence image results showed almost all injected BMSCs were accumulated in *** vivo anti-tumor tests demonstrated that only when the BMSCs transfected with thymidine kinase that could significant inhibit the growth of tumor cells. Conclusions:The novel non-viral vector spermine-pullulan could transfect the BMSCs efficiently and had low cytotoxic in vitro. BMSCs

关键词： Bone marrow-derived mesenchymal stem cells non-viral vector Ganciclovir/HSV-tk pulmonary targeting

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The enhancement effect of borneol on pharmacodynamics in rat brain of anticancer drug Irinotecan

The enhancement effect of borneol on pharmacodynamics in rat...

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2012年中国药物制剂大会——中国药学会药剂专业委员会年会、亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者：曹阳李范珠 College of Pharmaceutical Science Zhejiang Chinese Medical University

Objective Irinotecan(CPT-11),a treatment for small cell lung cancer(SCLC),has curative effect on patients with brain metastases from ***,due to the function of Blood Brain Barrier(BBB),the concentration of CPT-11 inside the brain is relatively low,which results in its poor curative ***,how to effectively improve the concentration of CPT-11 inside the brain without increasing its dosage has great importance to the prevention of SCLC-induced brain metastases or treatment of this disease. Traditional Chinese medicine bomeol can increase the permeability across the Blood Brain *** research aimed to study the positive effect of synthetic borneol to increase CPT-11's permeability across the BBB. Method This article firstly brought forward the idea to adopt intracephalic concentration of HA and 5-HT as an indicator to assess the synthetic borneol's role in promoting CPT-11's permeability across *** on one hand,due to its low concentration,it is hard to detect intracephalic CPT-11 concentration directly;one the other hand,CPT-11 and its metabolite could cause intracephalic concentration of HA and 5-HT to *** rats' oral administration of CPT-11 of different dosages,microdialysis probe was inserted through the previously embeded catheter,and microdialysis was conducted with the speed of 2ul/*** were collected every *** collecting for 1 hour,CPT-11 was injected into the caudal vein at 20mg/kg.8 hours of microdialysis was conducted after the administration of *** HPLC,conentrations of HA and 5-HT in dialysates were detected,and concentration-time curve was plotted. Results As shown in the results,compared with control,in groups of middle-or high-level of borneol,a striking increase of intracephalic 5-HT can be seen after administration of CPT-11,and the increase in 5-HT has positive correlation with the dosage of borneol. Conclusion Thus,this research shows that middle-or high-level of borneol could improv

关键词： Borneol Irinotecan 5-HT HA Blood Brain Barrier

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Compare of PLA microparticles and alum as adjuvant for H5N1 influenza split vaccine:adjuvanticity evaluation and preliminary mechanism analysis

Compare of PLA microparticles and alum as adjuvant for H5N1 ...

引用

2012年中国药物制剂大会——中国药学会药剂专业委员会年会、亚洲阿登制药技术研讨会暨国际控释协会中国分会年会

作者： Weifeng Zhang,Lianyan Wang.Yuan Liu,Xiaoming Chen,Jiahui Li,Guanghui Ma National Key Laboratory of Biochemical Engineering,Institute of Process Engineering,Chinese Academy of Sciences,Beijing, 100190,PR China

Objective:Increasing number of human infections of highly pathogenic H5N1 influenza has accentuated the urgence to develop safe and effective vaccines to prevent a potential influenza *** are required to improve the immune response to influenza split vaccine which is less reactogenic than pathogen-based *** aim of this study is to evaluate the capability of PLA microparticles and alum to improve the immunogenicity of H5N1 split vaccine and to illuminate their immunopotentiation mechanisms. Methods:PLA microparticles were prepared by premix membrane emulsification combined with emulsion-solvent evaporation ***-specific antibodies response in sera collected from vaccinated mice were detected by ELISA(IgM,IgG,IgG1, IgG2a,IgG2b)and hemagglutination inhibition *** activation,generation of effector/effector memory T cells,and dentritic cell maturation in spleen were evaluated by flow *** vivo imaging and immunohistochemistry were performed to assess antigen retention at injection site and local inflammation respectively. Results & Conclusion:PLA microparticles were spherical in shape with smooth surface,and had narrow size distribution(average size of about 800 nm)and negative surface *** with alum,PLA microparticles induced comparable IgG titers, significantly enhanced IgM and HI titers,more Th1 cytokines(IFN-γ,IL-2,and IL-12)-secreting splenocytes,and higher activation level of lymphocytes in *** indicated that antigen adjuvanted by alum remain at the injection site for significantly longer time and induced severe local ***,PLA microparticles accelerated antigen clearance from injection site,inducing milder *** above revealed that PLA microparticles had stronger adjuvanticity than alum to enhance the immunogenicity of H5N1 influenza split vaccine,improving both humoral and cellular immune ***'s more,PLA microparticles induced milder local inflammat

关键词： Microparticles alum vaccine adjuvant immunopotentiation mechanism

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