Study of Preparation and in Vitro Characterization of Zoledronic Acid Cationic Liposomes
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1 0.1% -80 PBS [9] (40 60 ) 10 d 5% 5% REFERENCES [1] WANI M C, TAYLOR H L, WALL M E, et al. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia [J]. J Am Chem Soc, 1971, 93(9): [2] SUGIURA H, OMOTO M, HIROTA Y, et al. Density and fine structure of peripheral nerves in various skin lesions of atopic dermatitis [J]. Arch Dermatol Res, 1997, 289(3): [3] YUAN S F, ZHU L J, ZHEGN W E, et al. Effect of baicalein combined paclitaxel on proliferation of human lung carcinoma cell [J]. Chin J Mod Appl Pharm( ), 2013, 30(12): [4] ZHANG J, YIN T J. Clinical observation of albumin-bound paclitaxel on 45 patients with advanced malignant tumors [J]. Chin J Hosp Pharm( ), 2014, 34(5): [5] PINCELLI C, FANTINI F, MASSIMI P, et al. Neuropeptides in skin from patients with atopic dermatitis: an immunohistochemical study [J]. Br J Dermatol, 1990, 122(6): [6] TOYODA M, MOROHASHI M. Morphological assessment of the effects of cyclosporine A on mast cell-nerve relationship in atopic dermatitis [J]. Acta Derm Venererol, 1998, 78(5): [7] LIU H, WU H Z, SHENG L. The study of dermatological liposomes [J]. Prog Pharm Sci( ), 2000, 24(3): [8] GUO X X. Preparation and skin permeation evaluation in vitro of bleomycin lipoge [J]. China Pharm( ), 2009, 12(12): [9] YANG T. Preparation and evaluation of paclitaxel-loaded PEGylated immunoliposome [D]. Shenyang: Shenyang Pharmaceutical University, [10] ZHANG B. Study on paclitaxel liposome and its freeze-dried preparation [D]. Shenyang: Shenyang Pharmaceutical University, [11] VERMA D D, VERMA S, BLUME G, et al. Particle size of liposomes influences dermal delivery of substances into skin [J]. Inter J Pharm, 2003, 258(1/2): [12] XIAO C. Preparation of paclitaxel magnetic nanoparticle liposome and its tissue distribution in mice [D]. Guangzhou: South China University of Technology, [13],,. [J]., 2002, 13(6): * ( ) Zeta DPPC DC-Chol 3 1 PBS 10 ml 60 min 5 min Zeta (106.76±1.94)nm 0.262±0.027 (38.54±0.99)% (3.42±0.27)% +(42.37±2.60)mV Weibull R943 B (2015) DOI: /j.cnki.issn Study of Preparation and in Vitro Characterization of Zoledronic Acid Cationic Liposomes CAI Xinjun 1, WANG Congyao 2, NI Jianjun 1, YAO Jun 1, XU Yingying 1, WANG Zeng 3* (1.Integrated Chinese and Western Medicine Hospital of Zhejiang Province, Hangzhou , China; 2.First People s Hospital of Xiaoshan, Hangzhou (2014KYB039) (2011A308) Tel: (0571) zjtcmcxj@163.com Tel: (0571) shulinsally@aliyun.com * Chin J Mod Appl Pharm, 2015 February, Vol.32 No.2 161
2 311200, China; 3.Zhejiang Cancer Hospital, Hangzhou , China) ABSTRACT: OBJECTIVE To prepare zoledronic acid cationic liposome, and evaluate its characteristics in vitro. METHODS Film dispersion method was used to prepare the zoledronic acid cationic liposome, then the single factor test of formulation and technology was investigated including the evaluation indexes as follows, the entrapment efficiency, drug loading amount, average particle size and Zeta potential. Moreover, its in vitro characterization was studied. RESULTS The prescription process was determined first, in detail, the ratio of DPPC and DC-Chol was 3 1, PBS hydrated volume was 10 ml, rotary evaporation time was 60 min, ultrasonic averaging time was 5 min, the average particle size, PDI, entrapment efficiency, drug loading and Zeta potential of cationic liposomes were (106.76±1.94 )nm, 0.262±0.027, (38.54±0.99)%, (3.42±0.27)%, +(42.37±2.60)mV, respectively. The profiles of release in vitro was expressed well by Weibull equationin. CONCLUSION The zoledronic acid cationic liposome which prepared by the film dispersion method has relatively high stability, this characteristics would be its basis for pharmacokinetic and pharmacodynamic research in future. KEY WORDS: zoledronic acid; cationic liposomes; characterization (zoledronic acid ZOL) ZOL [1-2] ZOL [3] (cationic liposomes CLPs) DNA RNA [4] CLPs [5] CLPs [6-8] (ZOL-CLPs) 1 Agilent 1200 ( Agilent ) Nano-ZS ( ) JEM-1200EX ( Jeol ) UV-1700 ( ) SCIENTZ- D ( ) R202 ( ) 3β-[N-(N,N - )] - (DC-Chol Sigma 017H8449V) (DPPC Corden T0343) ( >98.8%) ( %) ZOL-CLPs DC-Chol DPPC ZOL ph 7.6 ZOL ZOL-CLPs 2.2 ZOL-CLPs Zeta ZOL-CLPs 2.3 ZOL Hypersil BDS C 18 (250 mm 4.6 mm 5 µm) - (10% 6.0 ml ml 50% ph 2.3)(10 90) 1.0 ml min nm 20 µl ZOL 162 Chin J Mod Appl Pharm, 2015 February, Vol.32 No
3 15.0~200 µg ml 1 A=30.926C r= (n=7) 2.4 ZOL-CLPs ZOL-CLPs ZOL-CLPs 10 min 2.0% ZOL-CLPs ZOL-CLPs ZOL-CLPs 30 min( r min 1 ) HPLC ZOL W 1 ZOL-CLPs CLPs HPLC ZOL-CLPs ZOL W 0 ZOL-CLPs EE=(W 0 W 1 )/W 0 100% DL=(W 0 W 1 )/W t 100% EE DL W 0 ZOL W 1 W t ZOL 2.5 ZOL ZOL-CLPs ZOL ZOL-CLPs( ZOL 1.80 mg) 1 ph 10.0 (37 0.5) (75 r min 1 ) h 0.22 µm ZOL DPPC DC-Chol DPPC DC-Chol 1 3(10 mg 30 mg) 1 1(20 mg 20 mg) 3 1(30 mg 10 mg) 7 1(35 mg 5 mg) ZOL-CLPs DPPC DC-Chol ZOL-CLPs (n=3) Tab. 1 Influence of the mass ratio of DPPC and DC-Chol on ZOL-CLPs(n=3) DPPC DC-Chol /% /% /nm Zeta /mv ± ± ± ± ± ± ± ± ± ± ± ± PBS PBS ml ZOL-CLPs 2 PBS PBS 5 ml 10 ml PBS 2 Tab. 2 PBS / ml PBS ZOL-CLPs (n=3) Influence of the volume of PBS on ZOL-CLPs(n=3) ZOL / mg ml 1 /% /% /nm ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± min ZOL-CLPs (2 min) (5 min) ZOL-CLPs (8 min) ZOL-CLPs ZOL 2 min 5 min DPPC DC-Chol(3 1) (3 ml) min Chin J Mod Appl Pharm, 2015 February, Vol.32 No.2 163
4 3 ZOL-CLPs (n=3) Tab. 3 Influence of the time of ultrasonography on ZOL-CLPs(n=3) / min / / /nm ± ± ± ± ± ± ± ± ± ± ± ± min ZOL (ph=7.6) (40 ) 45 min 15 min 5 min 4 ZOL-CLPs Zeta ZOL-CLPs 1 4 (n=3) Tab. 4 The result of authenticate test(n=3) /nm /% /% Zeta / mv ± ± ± ± ± % 8 h 57.49% 36 h % 2 2 ZOL ZOL-CLPs (n=3) Fig. 2 Release profiles in vitro of ZOL and ZOL-CLPs (n=3) CLPs Higuchi Weibull ZOL-CLPs ZOL-CLPs Weibull lnln(1/1 Q)= lnt r= Q t 5 5 ZOL-CLPs Tab. 5 Fitting result of release curve of ZOL-CLPs r Q= t ln(1 Q)= t Higuchi Q= t 1/ Weibull lnln(1/1 Q)= lnt ZOL-CLPs ( ) Fig. 1 TEM photograph of ZOL-CLPs ( ) 3.3 ZOL ZOL-CLPs ZOL 5 h 94.13% ZOL-CLPs 2 h 4 DC-Chol DC-Chol DC-Chol DPPC DC-Chol [9] DPPC ZOL DPPC 164 Chin J Mod Appl Pharm, 2015 February, Vol.32 No
5 ZOL-CLPs ZOL-CLPs ZOL-CLPs ZOL ZOL-CLPs REFERENCES [1] ROGERS T L, HOLEN I. Tumour macrophages as potential targets of bisphosphonates [J]. J Transl Med, 2011(9): 177. Doi: / [2] WINTER M C, COLENAN R E. Bisphosphonates in the adjuvant treatment of breast cancer [J]. Clin Oncol (R Coll Radiol), 2013, 25(2): [3] DE LUCA A, LAMURA L, GALLO M, et al. Pharmacokinetic evaluation of zoledronic acid [J]. Expert Opin Drug Metab Toxicol, 2011, 7(7): [4] TROS DE IlARDUYA C, DUZGUNES N. Delivery of therapeutic nucleic acids via transferrin and transferrin receptors: lipoplexes and other carriers [J]. Expert Opin Drug Deliv, 2013(11): [5] HE J, LUSTER T A, THORPE P E. Radiation-enhanced vascular targeting of human lung cancers in mice with a monoclonal antibody that binds anionic phosphorlipids [J]. Clin Cancer Res, 2007, 13(17): [6] JI L, CHANG S, HE B, et al. Preparation of stealth cationic liposome loaded with doxorubicin and cell studies in vitro [J]. West China J Pharm Sci( ), 2012, 27(1): [7] RONG P P, SONG J C. Preparation of ph-sensitive procationic liposomes and tumor distribution study in mice [J]. Chin Pharm J( ), 2012, 47(6): [8] HO EA, RAMSAY E, GINJ M, et al. Characterization of cationic liposome formulations designed to exhibit extended plasma residence times and tumor vasculature targeting propertie [J]. J Pharm Sci, 2010, 99(6): [9] HE Z F, LIU D Y, ZENG S. Study on preparation of ampelopsin liposomes [J]. China J Chin Mater Med( ), 2008, 33(1): * ( ) h ph 24 h ph 2010 >99%( 0 h) ph 24 h R944.1 B (2015) DOI: /j.cnki.issn Study on the Stability of Vidarabine Monophosphate in Pediatric Electrolyte Supplements Injection HE Jian 1, ZHANG Yan 2* (1.The First Hospital of Hubei Laohekou, Laohekou , China; 2.Hunan Xiangtan Institute for Food and Drug Control, Xiangtan , China) ABSTRACT: OBJECTIVE To investigate the stability of vidarabine monophosphate for injection in Pediatric Electrolyte Tel: @qq.com @qq.com * Tel: Chin J Mod Appl Pharm, 2015 February, Vol.32 No.2 165
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