Abstract��
OBJECTIVE To synthesize a new drug delivery system of polyaldehyde Dex coupled with SA-10-HCPT and to study the HCPT release in vitro and the anti-tumor activity in vivo. METHODS The new drug delivery system was prepared by polyaldehyde Dex coupled with SA-HCPT��grafted with mPEG-adipic dihydrazide monohydrazone and cross-linked with adipic dihydrazide. RESULTS The conjugate formed micelle with a diameter of 100 nm in water��which could achieve passive targeting of tumor tissue concentration. The drug loading efficiency achieved 5.63%. The drug release processes accorded with kinetic equation Rc=Atn1/(B+Ctn2) in the buffer solution. The release rate of HCPT from this conjugate in pH 5.4 buffer was much higher than that in the environment of pH 7.4 and pH 4.5. The tumor inhibition of the conjugate was similar to that of HCPT while the toxicity in vivo was significantly reduced. CONCLUSION The structure of the conjugate is unstable in acidic environment��and the drug is released pH-sensitively. The mice survival rate is significantly improved because of the significant slow-release property. Therefore��the conjugate can be developed as a novel prodrug.
DENG Sheng-Song,
LIU Lu,
YAO Ri-Sheng etc
.Preparation of Dextran Nanogel Conjugates of HCPT with Acid-Sensitive Spacer and Its Properties[J] Chinese Pharmaceutical Journal, 2012,V47(12): 965-969
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[1]
ZHANG D Y. Nano Pharmacology(����ҩ��ѧ)[M].1sted. Beijing��Chemical Industry Press�� 2006��13-33.[2] BASAN H�� G��M��SDERELIOLU M�� TEYFIK O M. Release characteristics of salmon calcitonin from dextran hydrogels for colon-specific delivery [J]. Eur J Pharm Biopharm�� 2007�� 65 (1)��39-46.[3] MEHVAR R. Dextrans for targeted and sustained delivery of therapeutic and imaging agents [J]. J Controlled Release�� 2000�� 69��1����1-25.[4] QIU F�� FENG J�� WU D Q�� et al. Nanosized micelles self-assembled from amphiphilic dextran-graftmethoxypolyethylene glycol/poly(e-caprolactone) copolymers[J]. Euro Polymer J�� 2009�� 45��4����1024-1031.[5] GAO J M�� GUO Y Z�� GU Z W�� et al. Micellization and drug controlled release of amphiphilic methoxy poly(ethylene glycol)-b-poly(D�� L-lactide-co-trimethylene carbonate)[J].Acta Polymer Sin (�߷���ѧ��)�� 2008��1��2����174-178.[6] SONG J C�� HUANG L�� CHEN J L. Study on preparation and in vitro release behavior of lung targeting hydroxycamptothecin liposomes[J]. Chin Pharm J(�й�ҩѧ��־)�� 2008�� 43(20)��1564-1568. [7] HE W�� WU Y�� LI D�� et al. Study on antitumor activity of chitosan chloride-coated hydroxycamptothecin nanoliposomes in mice[J]. Chin Pharm J(�й�ҩѧ��־)�� 2006�� 41(17)��1328-1330.[8] HONG M H�� ZHU S J�� JIANG Y Y�� et al. Novel anti-tumor strategy��PEG-hydroxycamptothecin conjugate loaded transferrin-PEG-nanoparticles[J]. J Controlled Release�� 2010�� 141��1����22-29.[9] ZHOU Y Y�� DU Y Z�� WANG L�� et al. Preparation and pharmacodynamics of stearic acid and poly (lactic-co-glycolic acid) grafted chitosan oligosaccharide micelles for 10-hydroxycamptothecin[J]. Int J Pharm�� 2010�� 393��1����143-151.[10] ARIANE B�� ANNE A P�� CORINE G�� et al. pH-sensitive double-hydrophilic block copolymer micellesfor biological applications[J]. Int J Pharm�� 2009�� 379��2����212-217.[11] KAREL U�� VLADIM�wR S. Polymeric anticancer drugs with pH-controlled activation [J]. Adv Drug Deliv Rev�� 2004�� 56��7����1023-1050.[12] LEE E S�� NA K�� BAE Y H. Super pH-sensitive multifunctional polymeric micelle[J]. Nano Lett�� 2005�� 5��2����325-329.[13] HENRY S M�� PIRIE C M�� HOFFMAN A S�� et al. pH-responsive poly (styrene-alt-maleic anhydride) alkylamide copolymers for intracellular drug delivery [J]. Biomacromolecules�� 2006�� 7��8����2407-2414.[14] PRABAHARAN M�� GRAILER J J�� PILLA S�� et al. Amphiphilic multi-arm-block copolymer conjugated with doxorubicin via pH-sensitive hydrazone bond for tumor-targeted drug delivery[J]. Biomaterials�� 2009�� 30��29����5757-5766.
2012, Vol. 47 
