Hydrosoluble 50% N-acetylation-thiolated chitosan complex with cobalt as a pH-responsive renal fibrosis targeting drugs.
About 50% N-acetylation-thiolated chitosan possessing good water solubility was modified from commercial low-molecular-weight chitosan. Chitosan performed obvious target toward renal tubular epithelial cells, and bivalent cobalt ions improved the renal fibrosis inflammation significantly. There were many complexation sites on chitosan after being modified with sulfydryl. So sulfydryl played a role of connecting bridge between chitosan and cobalt ions. Then, this N-acetylation-thiolated chitosan cobalt (NTCC) nanocomplex was designed. The nanocomplex showed excellent stability under normal physiological conditions, and cobalt would be released from the biomaterials in acidic environment. As it was affected by inflammation, the pH in renal fibrosis lesion region was acidic. So there was a specific drug release process happening in lesion region. And drug release efficiency was determined by acidity, which demonstrated that lower the acidity, the faster and more the cobalt ion release. When this nanocomplex was intraperitoneally injected into ureter-obstructed mice, obvious attenuation of fibrotic progression was shown. It was demonstrated that NTCC exhibited special renal-targeting capacity and could be chosen as drug for treating renal fibrosis.
a Department of Chemistry, College of Chemistry and Chemical Engineering , South China University of Technology , Guangzhou , China.
Min
M
Li
b State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease , Nanfang Hospital, Southern Medical University , Guangzhou , China.
Lishan
L
Tan
a Department of Chemistry, College of Chemistry and Chemical Engineering , South China University of Technology , Guangzhou , China.
Liangfeng
L
Tang
b State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease , Nanfang Hospital, Southern Medical University , Guangzhou , China.
Aiqing
A
Li
a Department of Chemistry, College of Chemistry and Chemical Engineering , South China University of Technology , Guangzhou , China.
Jianqiang
J
Hu
D000107:Acetylation; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D003035:Cobalt / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005355:Fibrosis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry; D051381:Rats; D012995:Solubility; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014517:Ureteral Obstruction / Q000628:therapy*
D001672:Biocompatible Materials; D013438:Sulfhydryl Compounds; D003035:Cobalt; D048271:Chitosan
Hydrosoluble chitosan; pH responsive; renal fibrosis; targeting drug; thiolated