PLGA微米与纳米载药颗粒用于药物携带与递送的比较研究
|
摘要
目的通过评价聚乳酸-羟基乙酸共聚物(polylactic acid-glycolic acid copolymer,PLGA)微米颗粒(micron particle,MP)与纳米颗粒(nanoparticle,NP)的表面特征、载药能力、药物缓释能力及细胞吞噬能力等方面来比较阐述PLGA纳米与微米颗粒在细胞预处理与修饰中的合理应用。方法分别制备PLGA纳米颗粒与微米颗粒,并进行表征;随后,比较其载药能力,并对药物的释放特征进行测定;最后,在不同时间点通过荧光强度评价两种颗粒与细胞结合或进入细胞的能力。结果所制备的纳米粒与微米颗粒粒径分别分布在200～300 nm和2～4μm;两种颗粒载药量相当,分别为14. 3%和14. 1%;在药物缓释方面,纳米颗粒存在显著的早期突释现象;微米颗粒释放缓慢,持续缓释可达一周左右;粒径相对小的纳米粒更容易进入或与细胞结合,共孵育12 h即达到最大值,微米颗粒相对较慢,最大值出现在共孵育24 h后。结论 PLGA纳米颗粒作为药物载体更适合于急性组织或细胞保护,微米颗粒更适合于慢性持续性保护。
Objective The surface characteristics,drug delivery capacity,chemical drug delivery ability,nucleic acid sustained release ability and cell phagocytosis of poly( lactic acid-glycolic acid)( polylactic acid-glycolic acid copolymer,PLGA) microparticles( micron particle,MP) and nanoparticles( nanoparticle,NP) were evaluated to compare the application of PLGA nanoparticles and micron particles in cell pretreatment and modification. Methods PLGA nanoparticles and microparticles were prepared and characterized respectively. Then,drug loading capacity was compared and drug release characteristics were determined. Finally,the ability of PLGA nanoparticles to bind to cells or enter cells was evaluated by fluorescence intensity at different time points. Results The particle size of the prepared nanoparticles and microparticles were distributed at 200-300 nm and 2-4 μm,respectively. The loading of the two particles was 14. 3% and 14. 1%,respectively. In the aspect of drug sustained release,the nanoparticles exhibited significant early burst release; the release of microparticles was slow and sustained release could reach about one week; the relatively small nanoparticles were easier to enter or combine with cells,and incubated for 12 hours. That is to say,the micron particles are relatively slow to reach the maximum value,and the maximum value appears after 24 hours of incubation. Conclusions PLGA nanoparticles are more suitable for acute tissue or cell protection,and microparticles are more suitable for chronic persistent protection.
Objective The surface characteristics,drug delivery capacity,chemical drug delivery ability,nucleic acid sustained release ability and cell phagocytosis of poly( lactic acid-glycolic acid)( polylactic acid-glycolic acid copolymer,PLGA) microparticles( micron particle,MP) and nanoparticles( nanoparticle,NP) were evaluated to compare the application of PLGA nanoparticles and micron particles in cell pretreatment and modification. Methods PLGA nanoparticles and microparticles were prepared and characterized respectively. Then,drug loading capacity was compared and drug release characteristics were determined. Finally,the ability of PLGA nanoparticles to bind to cells or enter cells was evaluated by fluorescence intensity at different time points. Results The particle size of the prepared nanoparticles and microparticles were distributed at 200-300 nm and 2-4 μm,respectively. The loading of the two particles was 14. 3% and 14. 1%,respectively. In the aspect of drug sustained release,the nanoparticles exhibited significant early burst release; the release of microparticles was slow and sustained release could reach about one week; the relatively small nanoparticles were easier to enter or combine with cells,and incubated for 12 hours. That is to say,the micron particles are relatively slow to reach the maximum value,and the maximum value appears after 24 hours of incubation. Conclusions PLGA nanoparticles are more suitable for acute tissue or cell protection,and microparticles are more suitable for chronic persistent protection.
引文
[1]陈红丽,刘瑞,南文滨.乳酸-羟基乙酸共聚物微球、纳米粒载药体系的研究进展[J].中国药房,2012(37):3525-3527.
[2] Makadia H K,Siegel S J. Poly Lactic-co-glycolic acid(PLGA)as biodegradable controlled drug delivery carrier[J]. Polymers,2011,3(3):1377-1397
[3] Scott R C,Rosano J M,Ivanov Z,et al. Targeting VEGF-encapsulated immunoliposomes to MI heart improves vascularity and cardiac function[J]. Faseb J,2009,23(10):3361-3367.
[4] Zhang J,Ding L,Zhao Y,et al. Collagen-targeting vascular endothelial growth factor improves cardiac performance after myocardial infarction[J]. Circulation,2009,119(13):1776-1784.
[5] Yu T X,Shuangtao M,Gary T,et al. Uncoupling protein 2 in cardiovascular health and disease[J]. Front Physiol,2018,9:1060.
[6] Mahboob T,Nawaz M,Tan T C,et al. Preparation of poly(dl-Lactide-co-Glycolide)nanoparticles encapsulated with periglaucine a and betulinic acid for in vitro anti-acanthamoeba and cytotoxicity activities[J]. Pathog,2018,7(3):62.
[7] Wright L,Rao S,Thomas N,et al. Ramizolencapsulation into extended release PLGA micro-and nanoparticle systems for subcutaneous and intramuscular administration:in vitro and in vivo evaluation[J]. Drug Dev Ind Pharm,2018,44(9):1-19.
[8] Li P,Asokanathan C,Liu F,et al. PLGA nano/micro particles encapsulated with pertussis toxoid(PTd)enhances Th1/Th17 immune response in a murine model[J]. Int J Pharm,2016,513(1-2):183-190.
[9] Rawat A,Bhardwaj U,Burgess D J. Comparison of in vitro-in vivo,release of Risperdal,Consta,microspheres[J]. Int J Pharm,2012,434(1-2):115-121.
[10] Zhang Z,Wang X,Li B,et al. Development of a novel morphological paclitaxel-loaded PLGA microspheres for effective cancer therapy:in vitro and in vivo evaluations[J]. Drug Deliv,2018,25(1):166.
[11] Lunardi C N,Gomes A J,Palepu S,et al. PLGA nano/microparticles loaded with cresyl violet as a tracer for drug delivery:characterization and in-situ hyperspectral fluorescence and 2-photon localization[J]. Mat Sci Eng C-Mater,2017,70(Pt 1):505-511.
[12] Beringhs A O,Santos F A,Machado C A,et al. Association of PLGA microspheres to carrier pellets by fluid bed coating:a novel approach towards improving the flowability of microparticles[J]. J Pharmaceut,2018,2018:1-12.
[13] Ho Y T,Poinard B,Kah J C. Nanoparticle drug delivery systems and their use in cardiac tissue therapy[J].Nanomedicine,2016,11(6):693-714.
[14] Cohen-Sela E,Teitlboim S,Chorny M,et al. Single and double emulsion manufacturing techniques of an amphiphilic drug in PLGA nanoparticles:formulations of mithramycin and bioactivity[J]. J Pharm Sci,2009,98(4):1452-1462.
[15]韩淑贤.鱼精蛋白包覆的乙肝疫苗PLGA纳米粒载体的制备研究[D].华中科技大学,2015.
[16] Liu Z,Li X,Xiu B,et al. A novel and simple preparative method for uniform-sized PLGA microspheres:preliminary application in antitubercular drug delivery[J].Colloid Surface B,2016,145:679-687.
[17] Zhang Liangming,Zhang Jinling,Ling Y,et al. Sustained release of melatonin from poly(lactic-co-glycolic acid)(PLGA)microspheres to induce osteogenesis of human mesenchymal stem cells in vitro[J]. J Pineal Res,2012,54(1):24-32.
[18] Qi F,Wu J,Fan Q,et al. Preparation of uniform-sized exenatide-loaded PLGA microspheres as long-effective release system with high encapsulation efficiency and bio-stability[J]. Colloid Surface B,2013,112(12m):492-498.
[19] Damla C,Altndal,Menems'e G. Melatonin releasing PLGA micro/nanoparticles and their effect on osteosarcoma cells[J]. J Microencapsul,2015,33(1):1.
[20] Wang H,Zhang G,Ma X,et al. Enhanced encapsulation and bioavailability of breviscapine in PLGA microparticles by nanocrystal and water-soluble polymer template techniques[J]. Eer J Pharm Biopharm,2017,115:177-185.
[21] Chen L,Mei L,Feng D,et al. Anhydrous reverse micelle lecithin nanoparticles/PLGA composite microspheres for long-term protein delivery with reduced initial burst[J]. Colloid Surface B,2017,163:146.
[2] Makadia H K,Siegel S J. Poly Lactic-co-glycolic acid(PLGA)as biodegradable controlled drug delivery carrier[J]. Polymers,2011,3(3):1377-1397
[3] Scott R C,Rosano J M,Ivanov Z,et al. Targeting VEGF-encapsulated immunoliposomes to MI heart improves vascularity and cardiac function[J]. Faseb J,2009,23(10):3361-3367.
[4] Zhang J,Ding L,Zhao Y,et al. Collagen-targeting vascular endothelial growth factor improves cardiac performance after myocardial infarction[J]. Circulation,2009,119(13):1776-1784.
[5] Yu T X,Shuangtao M,Gary T,et al. Uncoupling protein 2 in cardiovascular health and disease[J]. Front Physiol,2018,9:1060.
[6] Mahboob T,Nawaz M,Tan T C,et al. Preparation of poly(dl-Lactide-co-Glycolide)nanoparticles encapsulated with periglaucine a and betulinic acid for in vitro anti-acanthamoeba and cytotoxicity activities[J]. Pathog,2018,7(3):62.
[7] Wright L,Rao S,Thomas N,et al. Ramizolencapsulation into extended release PLGA micro-and nanoparticle systems for subcutaneous and intramuscular administration:in vitro and in vivo evaluation[J]. Drug Dev Ind Pharm,2018,44(9):1-19.
[8] Li P,Asokanathan C,Liu F,et al. PLGA nano/micro particles encapsulated with pertussis toxoid(PTd)enhances Th1/Th17 immune response in a murine model[J]. Int J Pharm,2016,513(1-2):183-190.
[9] Rawat A,Bhardwaj U,Burgess D J. Comparison of in vitro-in vivo,release of Risperdal,Consta,microspheres[J]. Int J Pharm,2012,434(1-2):115-121.
[10] Zhang Z,Wang X,Li B,et al. Development of a novel morphological paclitaxel-loaded PLGA microspheres for effective cancer therapy:in vitro and in vivo evaluations[J]. Drug Deliv,2018,25(1):166.
[11] Lunardi C N,Gomes A J,Palepu S,et al. PLGA nano/microparticles loaded with cresyl violet as a tracer for drug delivery:characterization and in-situ hyperspectral fluorescence and 2-photon localization[J]. Mat Sci Eng C-Mater,2017,70(Pt 1):505-511.
[12] Beringhs A O,Santos F A,Machado C A,et al. Association of PLGA microspheres to carrier pellets by fluid bed coating:a novel approach towards improving the flowability of microparticles[J]. J Pharmaceut,2018,2018:1-12.
[13] Ho Y T,Poinard B,Kah J C. Nanoparticle drug delivery systems and their use in cardiac tissue therapy[J].Nanomedicine,2016,11(6):693-714.
[14] Cohen-Sela E,Teitlboim S,Chorny M,et al. Single and double emulsion manufacturing techniques of an amphiphilic drug in PLGA nanoparticles:formulations of mithramycin and bioactivity[J]. J Pharm Sci,2009,98(4):1452-1462.
[15]韩淑贤.鱼精蛋白包覆的乙肝疫苗PLGA纳米粒载体的制备研究[D].华中科技大学,2015.
[16] Liu Z,Li X,Xiu B,et al. A novel and simple preparative method for uniform-sized PLGA microspheres:preliminary application in antitubercular drug delivery[J].Colloid Surface B,2016,145:679-687.
[17] Zhang Liangming,Zhang Jinling,Ling Y,et al. Sustained release of melatonin from poly(lactic-co-glycolic acid)(PLGA)microspheres to induce osteogenesis of human mesenchymal stem cells in vitro[J]. J Pineal Res,2012,54(1):24-32.
[18] Qi F,Wu J,Fan Q,et al. Preparation of uniform-sized exenatide-loaded PLGA microspheres as long-effective release system with high encapsulation efficiency and bio-stability[J]. Colloid Surface B,2013,112(12m):492-498.
[19] Damla C,Altndal,Menems'e G. Melatonin releasing PLGA micro/nanoparticles and their effect on osteosarcoma cells[J]. J Microencapsul,2015,33(1):1.
[20] Wang H,Zhang G,Ma X,et al. Enhanced encapsulation and bioavailability of breviscapine in PLGA microparticles by nanocrystal and water-soluble polymer template techniques[J]. Eer J Pharm Biopharm,2017,115:177-185.
[21] Chen L,Mei L,Feng D,et al. Anhydrous reverse micelle lecithin nanoparticles/PLGA composite microspheres for long-term protein delivery with reduced initial burst[J]. Colloid Surface B,2017,163:146.