title: Development of a More Efficient Albumin-Based Delivery System for Gambogic Acid with Low Toxicity for Lung Cancer Therapy.
abstract: Gambogic acid (GA) has been proven to be a potent chemotherapeutic agent for the treatment of lung cancer in clinical trials. However, GA is limited in its therapeutic value by properties such as poor water solubility and low chemical stability. In clinical trials, cationic arginine (Arg) was added to solubilize GA, and this may also cause other side effects. Here, we have designed and developed a more efficient human serum albumin (HSA)-based delivery system for GA with low toxicity which helps improve its solubility, chemical stability and increases its antitumor efficacy. The GA-HSA nanoparticles (NPs) were prepared by albumin-bound (nabTM) technology, with a particle size of 135.2 ± 35.03 nm, a zeta potential of -21.81 ± 1.24 mV, and a high entrapment efficiency. Compared with GA-Arg solution, the physical and chemical stability of the NPs were improved when stored at pH 7.4 in PBS or freeze-dried. The in vitro drug release showed that GA-HSA NPs had a more sustained release than GA-Arg solution. Furthermore, HSA NPs improved the therapeutic efficacy of GA and were less toxic compared with GA-Arg solution in A549-bearing mice. Therefore, this delivery system is a promising polymeric carrier for GA when used for tumor therapy.
authors.affiliation: Normal College, Shenyang University, No.54, Lianhe Road, Shenyang, 110044, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Kelun Pharmaceutical Co., Ltd, Tianjin, 300450, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
authors.affiliation: Normal College, Shenyang University, No.54, Lianhe Road, Shenyang, 110044, China. yzx_syu@126.com.
authors.forename: Zaixing
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity*; D065546:Drug Liberation; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D012709:Serum Albumin / Q000737:chemistry / Q000633:toxicity*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects* / Q000502:physiology; D044004:Xanthones / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D012709:Serum Albumin; D044004:Xanthones; C052659:gambogic acid
keywords: antitumor; gambogic acid; human serum albumin; nanoparticles; stability