title: Water-soluble gambogic acid PEGylated prodrugs: synthesis, characterization, physicochemical properties and in vitro hydrolysis.
abstract: A series of poly(ethylene glycol) (PEG) prodrugs of gambogic acid (GA) with different molecular weight which used L-leucine as spacer were synthesized and characterized by FT-IR, 1H NMR and TOF MS. Drug loading capability, analyzed by UV spectrum, was 17.48, 9.26, 3.99, and 1.79%, aqueous solubility of the prodrugs was determined to be 1750, 1250, 800, and 645 mg/ml, respectively. The drug release from prodrugs was investigated under simulated in vivo conditions whose half-time (t1/2) in plasma ranged from 1.26 to 6.12 h. The effect of temperature on drug release was studied at four different temperatures and activation energy was determined as well. The stability of the prodrugs was improved in parallel with increasing molecular weight of PEG while prodrug yields and drug loading capability were reduced.
authors.affiliation: College of Pharmacy, China Pharmaceutical University, Nanjing, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Tang
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Hai
authors.initials: H
authors.lastname: Ye
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
authors.forename: Wenbin
authors.initials: W
authors.lastname: Shen
authors.forename: Qineng
authors.initials: Q
authors.lastname: Ping
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry; D002021:Buffers; D002627:Chemistry, Physical; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007930:Leucine / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D011092:Polyethylene Glycols / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D044004:Xanthones / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002021:Buffers; D011355:Prodrugs; D044004:Xanthones; D011092:Polyethylene Glycols; C052659:gambogic acid; D007930:Leucine