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吡诺克辛钠-层状双氢氧化物纳米片及插层纳米粒复合物滴眼液的研究

池慧波, 许婷婷, 陈红艳, 操锋

池慧波, 许婷婷, 陈红艳, 操锋. 吡诺克辛钠-层状双氢氧化物纳米片及插层纳米粒复合物滴眼液的研究[J]. 中国药科大学学报, 2016, 47(4): 448-456. DOI: 10.11665/j.issn.1000-5048.20160410
引用本文: 池慧波, 许婷婷, 陈红艳, 操锋. 吡诺克辛钠-层状双氢氧化物纳米片及插层纳米粒复合物滴眼液的研究[J]. 中国药科大学学报, 2016, 47(4): 448-456. DOI: 10.11665/j.issn.1000-5048.20160410
CHI Huibo, XU Tingting, CHEN Hongyan, CAO Feng. Ophthalmic solution of pirenoxine sodium-layered double hydroxide nanosheets and intercalated nanoparticles[J]. Journal of China Pharmaceutical University, 2016, 47(4): 448-456. DOI: 10.11665/j.issn.1000-5048.20160410
Citation: CHI Huibo, XU Tingting, CHEN Hongyan, CAO Feng. Ophthalmic solution of pirenoxine sodium-layered double hydroxide nanosheets and intercalated nanoparticles[J]. Journal of China Pharmaceutical University, 2016, 47(4): 448-456. DOI: 10.11665/j.issn.1000-5048.20160410

吡诺克辛钠-层状双氢氧化物纳米片及插层纳米粒复合物滴眼液的研究

基金项目: 国家自然科学基金资助项目(No.81373362);中央高校基本科研业务费专项基金资助项目(No.PT2014YX0054)

Ophthalmic solution of pirenoxine sodium-layered double hydroxide nanosheets and intercalated nanoparticles

  • 摘要: 为考察新型药物载体层状双氢氧化物(LDH)纳米片在眼部给药系统的应用,采用LDH纳米片为载体,羧甲基纤维素钠(CMC)为稳定剂,吡诺克辛钠(PRN)为模型药物,制备CMC-PRN-LDH纳米片复合物;采用共沉淀法制备PRN-LDHs插层纳米粒复合物。通过X射线衍射、原子力显微镜、透射电镜、激光粒度仪等对LDH纳米片、CMC-LDH纳米片复合物及两种载药-LDH纳米复合物理化性质进行研究。通过体外稳定性、体外释放、家兔泪液滞留实验比较了两种载药-LDH纳米复合物的差异。结果显示,CMC-PRN-LDH纳米片复合物相对稳定,而PRN-LDHs插层纳米粒稳定性较差,二者12 h体外累积释放百分率分别为70.44%和44.21%。CMC-PRN-LDH纳米片复合物滴眼液的AUC0-6 h和MRT分别为市售滴眼液的4.18和1.79倍,而PRN-LDHs插层纳米粒复合物滴眼液眼部滞留结果差异较大。CMC-PRN-LDH纳米片复合物滴眼液对眼部无刺激性。上述结果表明,LDH纳米片可作为眼部给药载体,能显著提高药物在角膜前的滞留时间。
    Abstract: The aim of this study was to evaluate the potential application of layered double hydroxide(LDH)nanosheets for ocular drug delivery. Using LDH nanosheets as carriers, carboxymethyl cellulose(CMC)as a stabilizer and pirenoxine sodium(PRN)as the model drug, CMC-PRN-LDH nanosheets were prepared. PRN-LDHs nanoparticles were synthesized via co-precipitation method. X-ray diffraction, atomic force microscopy, transmission electron microscopy and laser particle sizer were employed to characterize the physicochemical properties of LDH nanosheets, CMC-LDH nanosheets and PRN-LDH nanocomposites. Stability, accumulative release in vitro and precorneal retention in vivo of both CMC-PRN-LDH nanosheets and PRN-LDHs nanoparticles were evaluated. It was found that CMC-PRN-LDH nanosheets were electrostatically stabilized by CMC absorbed on the surface of LDH nanosheets, but PRN-LDHs nanoparticles aggregated in phosphate buffered saline. 12-hr accumulative release percentage of PRN from CMC-PRN-LDH nanosheets and PRN-LDHs nanoparticles were 70. 44% and 44. 21% in vitro, respectively. Compared with the commercial PRN eye drops, there existed 4. 18-fold increase in AUC0-6 h and 1. 79-fold in mean retention time of CMC-PRN-LDH nanosheets. Negligible levels of PRN-LDHs nanoparticles might be attributed to inter-groups difference. Draize test showed that CMC-PRN-LDH nanosheets were non-irritant to the rabbit eyes after single and repeated dosing. It suggest that this novel LDH nanosheet could be a promising carrier for ocular drug delivery with prolonged residence time.
  • [1] du Toit LC,Pillay V,Choonara YE,et al.Ocular drug delivery—a look towards nanobioadhesives[J].Expert Opin Drug Deliv,2011,8(1):71-94.
    [2] Achouri D,Alhanout K,Piccerelle P,et al.Recent advances in ocular drug delivery[J].Drug Dev Ind Pharm,2013,39(11):1599-1617.
    [3] Qin ZG,Cao F,Ping QN,et al.Layered double hydroxides and their applications in drug delivery systems[J].Prog Pharm Sci (药学进展),2013,37(12):615-622.
    [4] Gu Z,Rolfe BE,Xu ZP,et al.Antibody-targeted drug delivery to injured arteries using layered double hydroxide nanoparticles[J].Adv Healthc Mater, 2012,1(5):669-673.
    [5] Balcomb B,Singh M,Singh S.Synthesis and characterization of layered double hydroxides and their potential as nonviral gene delivery vehicles[J].Chemistry Open,2015,4(2):137-145.
    [6] Tuncelli G,Ay AN,Zümreoglu-Karan B.5-Fluorouracil intercalated iron oxide@layered double hydroxide core-shell nano-composites with isotropic and anisotropic architectures for shape-selective drug delivery applications[J].Mater Sci Eng C Mater Biol Appl,2015,55:562-568.
    [7] Cao F, Wang YJ, Ping QN, et al. Zn-Al-NO3-layered double hydroxides with intercalated diclofenac for ocular delivery[J].Int J Pharm,2011,404(1/2):250-256.
    [8] Wang YJ, Cao F, Ping QN. Preparation and characterization of diclofenac sodium layered double hydroxide nanohybrids[J].J China Pharm Univ (中国药科大学学报),2009,40(4):321-326.
    [9] Zhang J,Chi HB,Cheng YJ,et al.Ophthalmic solution of thiolated chitosan-pirenoxine sodium-layered double hydroxides hybrid nanocomposites[J].J China Pharm Univ (中国药科大学学报),2015,46(2):201-208.
    [10] Liang D,Yue W,Sun G,et al.Direct synthesis of unilamellar Mg,Al-LDH nanosheets and stacking in aqueous solution[J].Langmuir,2015,31(45):12464-12471.
    [11] Nicolosi V,Chhowalla M,Kanatzidis MG,et al.Liquid exfoliation of layered materials[J].Science,2013,340(6139):1226419.
    [12] Wang Q,O′Hare D.Large-scale synthesis of highly dispersed layered double hydroxide powders containing delaminated single layer nanosheets[J].Chem Commun,2013,49(56):6301-6303.
    [13] Wang Q,O′Hare D.Recent advances in the synthesis and application of layered double hydroxide(LDH)nanosheets[J].Chem Rev,2012,112(7):4124-4155.
    [14] Kang HL,Huang GL,Ma SL,et al.Coassembly of inorganic macromolecule of exfoliated LDH nanosheets with cellulose[J].J Phys Chem C,2009,113(21):9157-9163.
    [15] Kang HL,Shu Y,Li Z,et al.An effect of alginate on the stability of LDH nanosheets in aqueous solution and preparation of alginate/LDH nanocomposites[J].Cabohydr Polym,2014,100(2):158-165.
    [16] Gu Z,Zuo HL,Li L,et al.Pre-coating layered double hydroxide nanoparticles with albumin to improve colloidal stability and cellular uptake[J].J Mater Chem B,2015,3(16):3331-3339.
    [17] Hibino T.A new method for preparation of nanoplates of Zn-Al layered double hydroxides[J].Appl Clay Sci,2011,54(1):83-89.
    [18] Wu QL,Olafsen A,Φrnulv BV,et al .Delamination and restacking of a layered double hydroxide with nitrate as counter anion[J].J Mater Chem,2005,15(44):4695-4700.
    [19] Wang Y,Zhu LY,Dong Z,et al.Preparation and stability study of norfloxacin-loaded solid lipid nanoparticle suspensions[J].Colloids Surf B Biointerfaces,2012,98(10):105-111.
    [20] Bugatti V,Gorrasi G,Montanari F,et al.Modified layered double hydroxides in polycaprolactone as a tunable delivery system:in vitro release of antimicrobial benzoate derivatives[J].Appl Clay Sci,2011,52(1):34-40.
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  • 刊出日期:  2016-08-24

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