title: Enhanced tumor delivery and antitumor response of doxorubicin-loaded albumin nanoparticles formulated based on a Schiff base.
abstract: A novel method was developed here to prepare albumin-based nanoparticles (NPs) for improving the therapeutic and safety profiles of chemotherapeutic agents. This approach involved crosslinking bovine serum albumin (BSA) using a Schiff base-containing vanillin, into NPs and loading doxorubicin (DOX) into the NPs by incubation. The resultant NPs (DOX-BSA-V-NPs) displayed a particle size of 100.5±1.3 nm with a zeta potential of -23.05±1.45 mV and also showed high drug-loading efficiency and excellent stability with respect to storage and temperature. The encapsulation of DOX into the BSA-V-NPs was confirmed by dynamic scanning calorimetry and Raman spectroscopy. DOX-BSA-V-NPs exhibited a significantly faster DOX release at pH 6.5 than pH 7.4, as well as in a solution with a higher glutathione concentration. In vitro studies showed that the cellular uptake of DOX-BSA-V-NPs was time-dependent, concentration-dependent, and faster than free DOX, while the cytotoxicity of DOX-BSA-V-NPs (IC50 value of 3.693 μg/mL) was superior to free DOX (IC50 value of 4.007 μg/mL). More importantly, DOX-BSA-V-NPs showed a longer mean survival time of 24.83 days, a higher tumor inhibition rate of 56.66%, and a decreased distribution in the heart than other DOX formulations in animal studies using a tumor xenograft model. Thus, the vanillin-based albumin NPs were shown here to be a promising carrier for tumor-targeted delivery of chemotherapeutic agents and, thus, should be further studied.
authors: School of Pharmacy, China Pharmaceutical University, Nanjing; School of Pharmacy, Yancheng Vocational Institute of Health Sciences, Yancheng, People's Republic of China.
authors: Fang
authors: F
authors: Li
authors: School of Pharmacy, China Pharmaceutical University, Nanjing.
authors: Chunli
authors: C
authors: Zheng
authors: School of Pharmacy, Yancheng Vocational Institute of Health Sciences, Yancheng, People's Republic of China.
authors: Junbo
authors: J
authors: Xin
authors: School of Pharmacy, China Pharmaceutical University, Nanjing.
authors: Fangcheng
authors: F
authors: Chen
authors: School of Pharmacy, Hampton University, Hampton, VA.
authors: Hua
authors: H
authors: Ling
authors: Department of Chemical Engineering, Northeastern University, Boston, MA, USA.
authors: Linlin
authors: L
authors: Sun
authors: Department of Chemical Engineering, Northeastern University, Boston, MA, USA; Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Thomas J
authors: TJ
authors: Webster
authors: Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
authors: Xin
authors: X
authors: Ming
authors: School of Pharmacy, China Pharmaceutical University, Nanjing.
authors: Jianping
authors: J
authors: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002151:Calorimetry; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006321:Heart / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D012545:Schiff Bases; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013059:Spectrum Analysis, Raman; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D012545:Schiff Bases; D012710:Serum Albumin, Bovine; D004317:Doxorubicin
keywords: Schiff base; albumin nanoparticles; anticancer response; doxorubicin; tumor delivery