title: Cefepime loaded O-carboxymethyl chitosan microspheres with sustained bactericidal activity and enhanced biocompatibility.
abstract: Cefepime (CFP) is a frequently used antibiotic for prevention of post-surgery infection. Systemic delivery of CFP in a bulk dose usually shows effective therapeutic effects, while cytotoxicity can also be generated. To avoid the drawback of systemic delivery of antibiotic, local and controlled administration of drug is being employed to prolong therapeutic effects and reduce cytotoxicity by sustaining drug release and minimizing drug exposure. In this work, CFP loaded polymer O-carboxymethyl chitosan (OCMC) microspheres (CFP-OCMC-MPs) were fabricated and their antimicrobial activity against Staphylococcus aureus as well as biocompatibility were evaluated. The microspheres possessed the spherical surface with diameter approximately 7 μm. Fourier transforms infrared spectral and wide-angle X-ray diffraction analysis showed that CFP was steadily incorporated. The drug loading content and encapsulation efficiency of the microspheres were 21.4 ± 0.5% and 42.3 ± 0.7%, respectively. The drug release profiles were found to be biphasic with an initial burst release followed by a gradual release phase, following the Higuchi model. In addition, the CFP-OCMC-MPs were able to kill all the bacteria cultured in suspension within 24 h and exhibited long-lasting bactericidal activity as demonstrated by inhibition zone study. Compared to CFP, CFP-OCMC-MPs showed a milder toxicity toward osteoblast-like cells over an 8 day period. All these results suggest that CFP-OCMC-MPs are endowed with sustained treatment of bacterial infection and enhanced biocompatibility.
authors.affiliation: a Xiangya School of Pharmaceutical Sciences, Central South University , Changsha , China.
authors.forename: Zhenbao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: b Department of Pharmaceutical Engineering , School of Chemistry and Chemical Engineering, Central South University , Changsha , China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: b Department of Pharmaceutical Engineering , School of Chemistry and Chemical Engineering, Central South University , Changsha , China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: c School of Pharmacy, Hunan University of Chinese Medicine , Changsha , China.
authors.forename: Dongming
authors.initials: D
authors.lastname: Peng
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000077723:Cefepime; D002460:Cell Line; D002511:Cephalosporins / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D008422:Materials Testing; D008826:Microbial Sensitivity Tests; D008863:Microspheres
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; C504164:O-carboxymethylchitosan; D000077723:Cefepime; D048271:Chitosan
keywords: Cefepime; O-carboxymethyl chitosan microspheres; bactericidal activity; biocompatibility; sustained drug release