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• Nghien cixu - Ky thu4t de dinh logng terpin hydrat cac the phern da phan vai dieu kien pic terpin va chuen nal phai tech khoi cac phan kink hen hqp Tai liOu tham khao 1.80 lite (2009), Ducyc di4n Vitt Nam IV, tr 596-597 Ducec dion Mk (USP 38) 2015, pp 5497-5498 Douglas A Skoog, James J Leary (1992), "Principles of instrumental analysis", A harcourt brace Jovanovich college publisher, the United States of America, pp 588, 592 Reich U A (2011), "Illustrated Handbook of Toxicology, Georg Thieme Verlag KG, Germany, pp 106-107 International conference on harmonization of technical requirements for registration of Pharmaceuticals for human use (2005), Validation of analytical procedure: Text and Methodology, pp 1-13 (Ngay nhan bai: 22/02/2017 - Ngay phan Nan: 21/03/2017 - Ngay duyat clang: 03/04/2017) Nghien cfru ditu the hydrogel nanocomposite tren chitosan va curcumin *lig dung tai tao mo Ding Thi Huynh Nguyen Tuin Anil', Nguyen Dai Hai', TrAn Le Bao Ha' Doan Nguyen Vie, Tran Ng9c Quyenv, Nguyen Thi Bich Tram3 iVien Khoa hoc Vat lieu Ong dung - Vien Han liim KHCN Viet Nam 'Khoo Sinh hoc, Dpi hoc Khoa hoc Tlf nhien Tp Ha Chi Minh 3Khoa Hoa hoc, Dai hoc Thu D6u Mat, Thanh pha Thu Dau Mat, Tinh Binh arcmg * E-mail: tnquyen@iams.vast.vn Summary A temperature-sensitive hydrogel based on chitosan-pluronic was prepared Copolymers were characterized by 1H-NMR spectroscopy Sol-gel phase transition behavior of the obtained hydrogel was rheologically determined indicating formation of gel when the temperature increased from 25°C to 46°C The copolymer solution may served as a dispersant system for preparing nanocurcumin by emulsification Nanocurcumine distribution ranged from to 10 nm in the thermosensitive copolymer solution and the hydrogel nanocomposite could form at 34°C and enhanced second-degreed bum healing effect in rats Keywords: Nanocurcumin, chitosan, Pluronic F127, thermal sensitive CP hydrogel 001 Vin de Cho den nhieu loai hydrogel sinh hoc duvc nghien civu va Ong dung y sinh Cac hydrogel ten ca sa chitosan cho they hieu qua vocrt tr6i tai tao mo va den truyen thuoc [11 Trong nghien cOu nay, chUng tdi dieu the hydrogel nhay nhiet ten ca so' chitosan-pluronic mang nanocucurmin Ong dung china lanh vet thuvng Pluronic cb ceu tr)c PEO-PPO-PEO, duvc sir dung nhu' mat to duvc lam tang da h6a tan cua thu6c Trong dO PPO le phan ky, nu'O'c &wig vai tr6 tao lien kat ngang vat 19 tao hydrgel tang nhiet da dung dich copolymer 12] Bien tinh chitosan vai pluronic tao deh xuet chitosan hem tan va nhpy cam nhiet de mang va nha cham cac host chat Curcumin cO tac dyng he trg china lanh vet &Krung nh6 cac dac tinh nhu, chang viem, chOng nhiem trong, chang oxy h6a, tang hinh m6 hat, kich thich nguyen bao sgi phat trien tao collagen Tuy nhien, curcumin rat kern tan va da hep thu thep nen hien nano h6a curcumin de tang sinh khd dung duvc quan tam [31 Ben canh hopt tinh cO Ich cua chitosan va nanocurcumin, vai dac tinh cua cac hydrogel, he nanocomposite hydrogel giOp bao phei vet thirang ngan can cac vi khuen xem nhap, but dich TAP CHI Dtroc HQC - 4/2017 (SO 492 NAM 57) kr vet thirang va gidp hO trg lanh h6a vet throng (4] • Vat li0u, phu'o'ng phi!" va thyv nghiOm H6a chOt Chitosan (MW-300 kD, 95% acetyl hoe), pluronic F127 (Mw: 12.500 g/mol, Acros Organics), p-nitrophenyl chloroformat (NPC) (BASF Corp), tetrahydrofuran (THF), dimethylformamid (DMF), 3-amino-1-propanol (99%, Acros Organic) TOng hqp copolymer chitosan- F127 0,25 g chitosan hoe tan dung dich HCI khuey 24 gite, sau dO dieu chinh pH ye 5,5 NPC- F127-OH Ong hqp then quy trinh 15 '61, duvc hoe tan nutec cat lanh 4°C Dung dich NPC-F127-OH duvc nhO tin tin vao dung dich chitosan lanh va khuey qua dem Dung dich duvc them tech vai mang cellulose de loai bo cac tap chat va dong kh6 de thu chitosan-pluronic F127 cho danh gia ceu trUc va thi nghiem With gia dac tinh nhay nhiet cue copolymer Chitosan-pluronic duvc hob tan nutec cat (5, 8, 10, 12, 15 va 20%) duvc khao sat kha nang 47 • Nghien aim - Kg thuot nhay nhiet a cac nhiet de: 4, 25, 30, 37 va 40°C bang phu'ong phap deo ngt.rac dung djch copolymer Diem nhiet de chuyen pha tao gel cua dung djch copolymer theo nhiet de duvc xac Binh tren may lu'u bien ten may HAAKE RheoStress 6000 Dieu the nanocomposite hydrogel Curcumin (100 mM) nho vao dung djch 15% copolymer (chitosan:pluronic = 1:15; dung djch nu*c va ethanol (9:1 v/v) sjeu am 15 phOt roj ce• quay loci bo dung m6i, dang kh6 de thu nanocomposite kith thulac va sau da haa tan mac cat lanh hat nanocurcumin, diem nhiet tao gel va danh gia hieu qua china bong Danh gid china lanh vet bong Chi.* nhet trang (Mus muscuius var albino) co luvng 28 - 30 g mua ter Vier) Pasteur Tp HO Chi Minh, duvc nuOi On dinh tuhn, can such !Ong a vOng lung va gay me bang h6n hap ketamin va ntrac (1:1) vai lieu luvng 0,02 ml/g the tong, rOi g8y bong nhiet vat de Tien hanh thi nghiem vai nhOm: d6i chang (kh6ng XeY 19), boi chitosan-pluronic hydrogel, boi nCur-CS-F127 va kern trj bang de (Biafine, Filar)) Theo doi tien trinh lanh h6a, danh gia m6 hoc sau 14 a Ket qua thuv nghiem va ban luen Ket qua teng hop copolymer nhay nhidt chitosan-pluronic Copolymer &vac tong hap lien ket giCra nhOm amin ten chitosan va NPC-pluronic Hinh cho they khong tin hieu pic cua p-NPC (5 - 7,4 va 8,3 ppm) Cac tin hieu the hien Ong Wang cua proton methylen cuai mach pluronic da ghep vao chitosan xu6t hien b 4,25 ppm Cac proton dec tru'ng cua pluronic va chitosan cOng dirqc ghi nhen Ket qua thu &vac cho they de tong hap citing copolymer ghep chitosan-pluronic 12 I F a ,a U- 45`A-1A1°101ti S 1S 11 11 111 • 111 • 11 I 11 I PM Hinh 1: PM 'H-NMR cua copolymer ghep chitosanpluronic F127 Khao sat ddc tinh nhay nhidt cue copolymer ghep chitosan-pluronic F127 Khi khao sat cac nong tao gel bang phirang phap deo nguvc, m6u chitosan-pluronic (t9 le 1:1 theo kin& luvng ghep) kh6ng the to gel Khi tang t9 le pluronic len, kha nang tao gel duvc hinh Cac chitosanpluronic t9 ghep 1:15 va 1:20 co gel hinh tot nhiet de 30-35°C Mk chitosan-pluronic 1:20 cho they gel c.6 the hinh nhiet de 25°C NW vey, nhiet de chuyen gel tang tiler) tang ham luvrig pluronic meu chitosan-pluronic Phirang phap lu'u bien hoc cOng cho they nhiet de chuyen gel cua dung djch 15% chitosan-pluronic xay a 35°C vai ghep a t9 le 1:15 Diem chuyen nhiet rat thich hap cho cac Ong dvng y sinh vi gen vai nhiet de ca the Ddnh gia hg hydrogel nanocomposite Phuvng phap dieu the he hydrogel china nanocurcumin nghien thu cho they nanocurcumin duvc dieu the dung djch chitosan-pluronic vai &rang kinh di rai 10 nm He phan tan tren c6 the chuyen nanocomposite hydrogel china 15% chitosanpluronic F127 tang nhiet len 35°C (hinh 2) Flanocurcumin Hinh 2: Chu* hoa sol-gel cua chitosan-F127 va hinh thai nanocurcumin 48 TAP CHI DUQC HQC - 4/2017 (SO 492 NAM 57) • Nghien ciru - Kji thOt Dinh gia Neu qua china lanh vet thuvng bong de Ket qua thin nghiem china lanh vet bong ten m6 hinh chuet cho they sau 14 ngey vet bong phi) vai nanocomposite hydrogel china nanocurcumin lanh gen nhu, hoan town co nhieu long mai mix tren mo tai tao D6i vai Ink thirang mai vet b6ng china lanh kha tot vai dO co vet thuang ten 95% Mau khong dieu tri thi vet bong chi china lanh khoang 80% (hinh 3) Hinh 3: Hinh anh qua trinh china lanh vet bang va d6 thi danh gia dO co vet Chuang Ket qua danh gia m6 hoc cho they cac hydrogel vai thu6c thirang mai Biafine Tuy nhien, meu mo khong gay di Ong, khong lam ngan can qua trinh dap Crng tai tao vai hydrogel composite cho trot tu' hinh binh thirang cua CU the Vet bong ph6 nanocomposite lap thuvng bi, bi va lap ca c6 trot tu' nhu, mau m6 hydrogel co tac dung day nhanh qua trinh tai to va lanh tu' nhien (hinh 4) Ket qua nghien ciru sa khai cho has vet thirang bong vai mat de collagen tai tao c6 trat they tiern Wang cua hydrogel ten ca sa chitosan mang ty,, nhieu mach mau va m6 hat hinh twang &rang nanocurcumin china lanh yet thu,ang ket qua phan tich mo hoc oh vet bOng duvc x6, l' Pr Hinh 4: Ket qua nhu6m h6a m6 Hematoxyline&Eosin cua: a) mo thutmg, b) m6 chug vcif Biafine va c) m6 chfia vOi hydrogel composite Ket luan Copolymer ghep nhay nhiet chitosan-pluronic duvc tong hap cong va sir dung nhu' chat nen cho tong hap nanocomposite hydrogel Dung dich copolymer mang nanocurcumin phan tan co diem chuyen nhiet giCra tang thai sol sang gel 0, 35°C, day la khoang nhiat de 19 twang cho cac thin nghiem oh vat lieu nanocomposite hydrogel china lanh vet thuvng ngoai da Ket qua thin nghiem butrc du cho they nanocomposite hydrogel tang cirang hieu qua china lanh vet bong de ten m6 hinh chi* TAP CHI DEW HQC - 4/2017 (SO 492 NAM 57) Lel cam an Nghien cCru tai tra 1361 Vien Han lam KHCN Wet Nam theo hap ding VAST03.08/17-18 Tai liOu tham khao Nguyen D H., Tran N Q., Nguyen C K (2013), "Tetronic-grafted chitosan hydrogel as an injectable and biocompatible scaffold for biomedical applications", Journal of Biomaterials Science, 24 (14), 1636-1648 Kamel A H (2002), "In vitro and in vivo evaluation of pluronic F127-based ocular delivery system for timolol maleate", Int J Pharm., 241, 47-55 49 • Nghiên ciru - Ky thOt Dania Akbika, Maliheh Ghadiria, Wojciech Chrzanowskia, Ramin Rohanizadeha (2014), "Curcumin as a wound healing agent", Life Sciences, 116,1-7 Zhoua H Y, Zhanga Y P., Zhang W F., Chen X G (2011), "Biocompatibility and characteristics of injectable chitosan-based thermosensitive hydrogel for drug delivery", Carbohydrate Polymers, 83,1643-1651 Nguyen Thi Tram Chau, Thi Hiep Nguyen, Tran Ngoc Quyen, Nguyen Cuu Khoa (2017), "Highly lipophilic pluronics-conjugated polyamidoamine dendrimer nanocarriers as potential delivery system for hydrophobic drugs", Materials Science and Engineering C: Materials for Biological Applications, 70,992-999 Choi J H., Joung Y K., Bae J W., Choi J W., Tran N Q., Park K D (2011), "Self-assembled nanogel of pluronic-conjugated heparin as a versatile drug nanocanier", Macromolecular Research, 19(2), 180-188 (Ngay nhan bai: 21/01/2017 - Ngay ph& bian: 15/02/2017 - Ngay duyat clang: 03/04/2017) Nghien cfru xay dtrng vithim dinh phuvng phap, LC-MS/MS dinh luyng dong thoi curcumin va chat chuytn hoa tetrahydrocurcumin huytt tuvng chu(it Hwang Thj Hong Anh'*, Hoing Van Dime, Le Thj Thu Huyen2 Nguyen Vin Long', Nguyen TrAn Linh' Truing Dui hoc Amy Ha Nal Vien Kie'm nghiOm thuoc Trung E-mail: honganh117@gmail.com Summary A specific and sensitive LC-MS/MS method was developed for the determination of curcumin (CUR) and tetrahydrocurcumin (THC) in mouse plasma Curcumin, tetrahydrocurcumin and internal standard (IS) were extracted from mouse plasma with tert-butyl methyl ether The analytes were chromatographed as follows: Kinetex column (100 mm x 2.1 mm, i.d; 1.7 pm); Mobile phase: acetonitrile-formic acid 0.05% (60:40, v/v); Detector: positive ion electrospray ionization (ESI) mass spectrometry with multi-reaction monitoring (MRM) Good linearity covered the concentration range of 0.5-500 ng/ml, with a limit of quantification of 0.5 ng/mL for both CUR and THC, each The intra- and inter-day precisions (CV) for either CUR and THC were both less than 15.0% and the accuracy was from 91.3 to 112.6% On practical application, the method proved suitable for pharmacokinetic study of CUR and THC in experimental mice and can be applicable to future bioavailablity study in human Keywords: Curcumin, tetrahydrocurcumin, LC-MS/MS, ESL Dot van Trong nhinng nam On day, curcumin (CUR) - hoot chat duvc chiet mat tu, cay ngha yang (Curcuma longa L.), dang thu htit duvc sy, quan tam Gila nganh Y hyc ten the g161 nhOng tac dyng sinh hyc vuvt trOi nhu, tinh khang khuan, khang virus, chang viem, tang cutmg mien Tuy nhien, CUR ft tan nuttc [21, sinh kha dung thap, bi chuyen haa manh qua gan, to mOt so san pham chuyen h6a (16 tetrahydrocurcumin (THC) la met chat c6 hoat tinh manh Tren the gi&i, phan Ian cac nghien aru danh gia SKD cilia CUR chi lien hanh dinh lityng CUR huyet twang [4, 51 Met s6 It nghien c&u dinh luvng ca CUR va chit chuyen h6a huyet tu,ang Ti Viet Nam, cho den nay, cac thong s6 duvc dOng hoc dm the pham chin CUR van chin duvc nghien dm day du Vi vey, bai bao trinh bay nghien cipu vai myc tieu xay Ong va tham dinh phuvng phap LC-MS/MS CO c10 dO nhey, dac hiau va chInh xac de dinh luvng 50 ding theyi CUR va chat chuyen h6a THC huyet twang chuOt thf nghiem Nguyen lieu va phu'ong phap nghien cuu Nguyen lieu Chit chuin + Curcumin (CUR) — Chun phong thi nghiem, ham luvng: 95,51% (nguyen tang) + Tetrahydrocurcumin (THC) — Chuan nha san xuat, ham luvng: 95,0%; am 0,09% + Glibenclamid (GBC) - Chun phong thi nghiem, ham luvng 100,1%, dO am 0,09% SO dyng lam chat nei chuan (IS) phuvng phap phan tfch Dung m6i, h6a chit: Dat tau chi& tinh khiet dung cho HPLC va LC/MS Huyit tuong treing: Lay tin cac chuOt nhat thf nghiem khang sip dying thuoc Phuvng phap nghien cu'u Khao sat dieu kien sac ky, khoi phi va phirang phap TAP CHI DUVC HQC - 4/2017 (SO 492 NAM 57) ... vai nhiet de ca the Ddnh gia hg hydrogel nanocomposite Phuvng phap dieu the he hydrogel china nanocurcumin nghien thu cho they nanocurcumin duvc dieu the dung djch chitosan- pluronic vai &rang kinh... tren c6 the chuyen nanocomposite hydrogel china 15% chitosanpluronic F127 tang nhiet len 35°C (hinh 2) Flanocurcumin Hinh 2: Chu* hoa sol-gel cua chitosan- F127 va hinh thai nanocurcumin 48 TAP CHI... vOi hydrogel composite Ket luan Copolymer ghep nhay nhiet chitosan- pluronic duvc tong hap cong va sir dung nhu' chat nen cho tong hap nanocomposite hydrogel Dung dich copolymer mang nanocurcumin
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