两亲性壳聚糖衍生物在药物递送中的研究进展
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摘要
壳聚糖是一种来源丰富的碱性多糖,具有良好的生物相容性和生物可降解性,但是其差的溶解性限制了壳聚糖在医药领域的应用。为了提高壳聚糖的溶解性,研究者对壳聚糖进行两亲性改性,通过选择不同的亲水、疏水基团,设计合成了两亲性壳聚糖衍生物。并利用其在水溶液中的自组装性能,形成两亲性壳聚糖纳米粒,用于多种药物的递送,以达到增加药物溶解性、稳定性、降低药物毒性和提高生物利用度等目的。本文综述了两亲性壳聚糖衍生物的合成方法,以及其在药物递送系统中的应用。
Chitosan( CS) is a natural alkaline polysaccharide with a rich source,exhibiting good biocompatibility and biodegradability,but poor solubility limits its application in the field of medicine.In order to overcome its shortcomings,amphiphilic chemical modification of CS is carried out; by selecting different hydrophilic and hydrophobic groups,amphiphilic chitosan derivatives( ACSs) were designed and synthesized.ACSs are easily self-assembled into amphiphilic chitosan nanocarriers( ACNs) in water,which are widely used in the delivery of multiple drugs to increase drug solubility,stability,reduce drug toxicity,as well as improve bioavailability.In this work,the synthesis methods of ACSs and their applications in drug delivery systems were reviewed.
Chitosan( CS) is a natural alkaline polysaccharide with a rich source,exhibiting good biocompatibility and biodegradability,but poor solubility limits its application in the field of medicine.In order to overcome its shortcomings,amphiphilic chemical modification of CS is carried out; by selecting different hydrophilic and hydrophobic groups,amphiphilic chitosan derivatives( ACSs) were designed and synthesized.ACSs are easily self-assembled into amphiphilic chitosan nanocarriers( ACNs) in water,which are widely used in the delivery of multiple drugs to increase drug solubility,stability,reduce drug toxicity,as well as improve bioavailability.In this work,the synthesis methods of ACSs and their applications in drug delivery systems were reviewed.
引文
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[25] LAI M,WANG J,TAN J,et al.Preparation,complexation mechanism and properties of nano-complexes of Astragalus polysaccharide and amphiphilic chitosan derivatives[J].Carbohydr Polym,2017(161):261-269.
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[34] JENA S K,SANGAMWAR A T.Polymeric micelles of amphiphilic graft copolymer ofα-tocopherol succinate-gcarboxymethyl chitosan for tamoxifen delivery:synthesis,characterization and in vivo pharmacokinetic study[J].Carbohydr Polym,2016(151):1162-1174.
[35] HUANG W T,LARSSON M,LEE Y C,et al.Dual drugloaded biofunctionalized amphiphilic chitosan nanoparticles:enhanced synergy between cisplatin and demethoxycurcumin against multidrug-resistant stem-like lung cancer cells[J].Eur J Pharm Biopharm,2016(109):165-173.
[36] OPANASOPIT P,SAJOMSANG W,RUKTANONCHAI U,et al. Methylated N-(4-pyridinylmethyl)chitosan as a novel effective safe gene carrier[J].Int J Pharm,2008,364(1):127-134.
[37] SHARMA D,SINGH J.Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymer and Their Nanomicelles for Nonviral Gene Delivery Applications[J]. Bioconjug Chem,2017,28(11):2772-2783.
[38] LIU Y,CHENG X J,DANG Q F,et al.Preparation and evaluation of oleoyl-carboxymethy-chitosan(OCMCS)nanoparticles as oral protein carriers[J]. J Mater Sci Mater Med,2012,23(2):375-384.
[39] SHELMA R,SHARMA C P.Submicroparticles composed of amphiphilic chitosan derivative for oral insulin and curcumin release applications[J].Colloids Surf B Biointerfaces,2011,88(2):722-728.
[2] MOHAMMED M A,SYEDA J,WASAN K M,et al.An Overview of Chitosan Nanoparticles and Its Application in Non-Parenteral Drug Delivery[J].Pharmaceutics,2017,9(4):53.
[3] MOTIEI M,KASHANIAN S,TAHERPOUR A A.Hydrophobic amino acids grafted onto chitosan:a novel amphiphilic chitosan nanocarrier for hydrophobic drugs[J].Drug Dev Ind Pharm,2017,43(1):1-11.
[4] YU X,MU Y,XU M,et al.Preparation and characterization of mucosal adhesive and two-step drug releasing cetirizine-chitosan nanoparticle[J]. Carbohydr Polym,2017(173):600-609.
[5] DE OLIVEIRA PEDRO R,SCHMITT C C,NEUMANN M G. Syntheses and characterization of amphiphilic quaternary ammonium chitosan derivatives[J]. Carbohydr Polym,2016(147):97-103.
[6] MOTIEI M,KASHANIAN S,LUCIA L A,et al.Intrinsic parameters for the synthesis and tuned properties of amphiphilic chitosan drug delivery nanocarriers[J].J Control Release,2017(260):213-225.
[7] EL FRAY M,NIEMCZYK A,PABIN-SZAFKO B.Chemical modification of chitosan with fatty acids[J]. Szafko,2012(17):29-36.
[8] MORENO P M,SANTOS J C,GOMES C P,et al.Delivery of splice switching oligonucleotides by amphiphilic chitosan-based nanoparticles[J]. Mol Pharm,2016,13(2):344-356.
[9] LARSSON M,HUANG W C,HSIAO M H,et al.Biomedical applications and colloidal properties of amphiphilically modified chitosan hybrids[J]. Prog Polym Sci,2013,38(9):1307-1328.
[10] MO R,JIN X,LI N,et al.The mechanism of enhancement on oral absorption of paclitaxel by N-octyl-O-sulfate chitosan micelles[J]. Biomaterials,2011,32(20):4609-4620.
[11] YOSHIOKA H,NONAKA K,FUKUDA K,et al.Chitosanderived polymer-surfactants and their micellar properties[J]. Biosci Biotechnol Biochem,1995,59(10):1901-1904.
[12] TANG S,HUANG Z,ZHANG H,et al.Design and formulation of trimethylated chitosan-graft-poly(ε-caprolactone)nanoparticles used for gene delivery[J]. Carbohydr Polym,2014(101):104-112.
[13] SIEVAL A B,THANOU M,KOTZE A F,et al.Preparation and NMR characterization of highly substituted Ntrimethyl chitosan chloride[J].Carbohydr Polym,1998,36(2-3):157-165.
[14] SONG Y,TANG C,YIN C.Enhanced antitumor efficacy of arginine modified amphiphilic nanoparticles co-delivering doxorubicin and i Sur-p DNA via the multiple synergistic effect[J].Biomaterials,2018(150):1-13.
[15] WU M,LONG Z,XIAO H,et al.Recent research progress on preparation and application of N,N,N-trimethyl chitosan[J].Carbohydr Res,2016(434):27-32.
[16] THANOU M,VERHOEF J C,MARBACH P,et al.N-trimethyl chitosan chloride(TMC)ameliorates the permeability and absorption properties of the somatostatin analogue in vitro and in vivo[J]. J Pharm Sci,2000,89(7):951-957.
[17] YE Z,GUO J,WU D,et al.Photo-responsive shell crosslinked micelles based on carboxymethyl chitosan and their application in controlled release of pesticide[J].Carbohydr Polym,2015(132):520-528.
[18] ZENG T,ZHANG Y,YAN Q,et al. Construction and in vitro evaluation of enzyme nanoreactors based on carboxymethyl chitosan for arginine deprivation in cancer therapy[J].Carbohydr Polym,2017(162):35-41.
[19] YOO H S,LEE J E,CHUNG H,et al.Self-assembled nanoparticles containing hydrophobically modified glycol chitosan for gene delivery[J]. J Control Release,2005,103(1):235-243.
[20] KARIMI Z,ABBASI S,SHOKROLLAHI H,et al.Pegylated and amphiphilic Chitosan coated manganese ferrite nanoparticles for p H-sensitive delivery of methotrexate:Synthesis and characterization[J].Mater Sci Eng C Mater Biol Appl,2017(71):504-511.
[21] DENG J,ZHANG Z,LIU C,et al.The studies of N-OctylN-Arginine-Chitosan coated liposome as an oral delivery system of Cyclosporine A[J].J Pharmacy and Pharmacol,2015,67(10):1363-1370.
[22] GABRIEL J S,GONZAGA V A M,POLI A L,et al.Photochemical synthesis of silver nanoparticles on chitosans/montmorillonite nanocomposite films and antibacterial activity[J].Carbohydr Polym,2017(171):202-210.
[23] PENG S,ZOU L,LIU W,et al.Hybrid liposomes composed of amphiphilic chitosan and phospholipid:Preparation,stability and bioavailability as a carrier for curcumin[J].Carbohydr Polym,2017(156):322-332.
[24] LI G,SONG P,WANG K,et al.An amphiphilic chitosan derivative modified by deoxycholic acid:preparation,physicochemical characterization,and application[J]. J Mater Sci,2015,50(6):2634-2642.
[25] LAI M,WANG J,TAN J,et al.Preparation,complexation mechanism and properties of nano-complexes of Astragalus polysaccharide and amphiphilic chitosan derivatives[J].Carbohydr Polym,2017(161):261-269.
[26] WU M,DONG H,GUO K,et al. Self-assemblied nanocomplexes based on biomimetic amphiphilic chitosan derivatives for protein delivery[J]. Carbohydr Polym,2015(121):115-121.
[27] SHARMA D,SINGH J.Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymer and Their Nanomicelles for Nonviral Gene Delivery Applications[J]. Bioconjug Chem,2017,28(11):2772-2783.
[28] MORENO P M D,SANTOS J C,GOMES C P,et al.Delivery of splice switching oligonucleotides by amphiphilic chitosan-based nanoparticles[J].Mol Pharm,2016,13(2):344-356.
[29] MAHMOOD A,LANTHALER M,LAFFLEUR F,et al.Thiolated chitosan micelles:Highly mucoadhesive drug carriers[J].Carbohydr Polym,2017(167):250-258.
[30] WANG B,HE C,TANG C,et al.Effects of hydrophobic and hydrophilic modifications on gene delivery of amphiphilic chitosan based nanocarriers[J]. Biomaterials,2011,32(20):4630-4638.
[31] SILVA D S,ALMEIDA A,PREZOTTI F G,et al.Self-aggregates of 3,6-O,O’-dimyristoylchitosan derivative are effective in enhancing the solubility and intestinal permeability of camptothecin[J]. Carbohydr Polym,2017(177):178-186.
[32] BOSSIO O,GMEZ-MASCARAQUE L G,FERNNDEZ-GUTIRREZ M,et al.Amphiphilic polysaccharide nanocarriers with antioxidant properties[J]. J Bioact Compat Pol,2014,29(6):589-606.
[33] DU H,YANG X,PANG X,et al.The synthesis,self-assembling, and biocompatibility of a novel Ocarboxymethyl chitosan cholate decorated with glycyrrhetinic acid[J].Carbohydr Polym,2014(111):753-761.
[34] JENA S K,SANGAMWAR A T.Polymeric micelles of amphiphilic graft copolymer ofα-tocopherol succinate-gcarboxymethyl chitosan for tamoxifen delivery:synthesis,characterization and in vivo pharmacokinetic study[J].Carbohydr Polym,2016(151):1162-1174.
[35] HUANG W T,LARSSON M,LEE Y C,et al.Dual drugloaded biofunctionalized amphiphilic chitosan nanoparticles:enhanced synergy between cisplatin and demethoxycurcumin against multidrug-resistant stem-like lung cancer cells[J].Eur J Pharm Biopharm,2016(109):165-173.
[36] OPANASOPIT P,SAJOMSANG W,RUKTANONCHAI U,et al. Methylated N-(4-pyridinylmethyl)chitosan as a novel effective safe gene carrier[J].Int J Pharm,2008,364(1):127-134.
[37] SHARMA D,SINGH J.Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymer and Their Nanomicelles for Nonviral Gene Delivery Applications[J]. Bioconjug Chem,2017,28(11):2772-2783.
[38] LIU Y,CHENG X J,DANG Q F,et al.Preparation and evaluation of oleoyl-carboxymethy-chitosan(OCMCS)nanoparticles as oral protein carriers[J]. J Mater Sci Mater Med,2012,23(2):375-384.
[39] SHELMA R,SHARMA C P.Submicroparticles composed of amphiphilic chitosan derivative for oral insulin and curcumin release applications[J].Colloids Surf B Biointerfaces,2011,88(2):722-728.