Surface-Eroding Poly(ortho ester amides) for Highly Efficient Oral Chemotherapy.
Two new poly(ortho ester amide) copolymers (POEA-4 and POEA-5) were synthesized via polycondensation of a new ortho ester diamine monomer with active esters of different aliphatic diacids. The kinetics of POEA mass loss and release of 5-FU were both nearly zero-order, suggesting predominantly surface-restricted polymer erosion and drug release. In vitro cytotoxicity tests demonstrated that both copolymers have excellent biocompatibility. In vivo acute toxicity tests suggested that oral administration of POEA-4 and POEA-5 did not cause any adverse effects on mice even at a very high dose (2000 mg/kg). In vivo antitumor efficacy against H22 transplanted tumors of 5-FU-loaded POEA tablets were fully examined. We envision that, with further optimization, POEA-based materials could have great potential as drug carriers for oral chemotherapy.
‡Engineering Research Center for Biomedical Materials, School of Life Science, Anhui University, 111 Jiulong Road, Hefei, Anhui Province 230601, P. R. China.
Bing
B
Wei
§School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu Province 214122, P. R. China.
Yangyang
Y
Tao
‡Engineering Research Center for Biomedical Materials, School of Life Science, Anhui University, 111 Jiulong Road, Hefei, Anhui Province 230601, P. R. China.
Xin
X
Wang
‡Engineering Research Center for Biomedical Materials, School of Life Science, Anhui University, 111 Jiulong Road, Hefei, Anhui Province 230601, P. R. China.|§School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu Province 214122, P. R. China.
Rupei
R
Tang
‡Engineering Research Center for Biomedical Materials, School of Life Science, Anhui University, 111 Jiulong Road, Hefei, Anhui Province 230601, P. R. China.
Jun
J
Wang
§School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu Province 214122, P. R. China.
Rui
R
Wang
§School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu Province 214122, P. R. China.
Liying
L
Qiu
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004058:Diffusion; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry*; D013499:Surface Properties; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D053769:Nanocapsules; C054694:polyoxyethyleneamine; D011092:Polyethylene Glycols; D005472:Fluorouracil
controlled release; oral chemotherapy; poly(ortho ester); surface erosion