title: Effect of pullulan nanoparticle surface charges on HSA complexation and drug release behavior of HSA-bound nanoparticles.
abstract: Nanoparticle (NP) compositions such as hydrophobicity and surface charge are vital to determine the presence and amount of human serum albumin (HSA) binding. The HSA binding influences drug release, biocompatibility, biodistribution, and intercellular trafficking of nanoparticles (NPs). Here, we prepared 2 kinds of nanomaterials to investigate HSA binding and evaluated drug release of HSA-bound NPs. Polysaccharides (pullulan) carboxyethylated to provide ionic derivatives were then conjugated to cholesterol groups to obtain cholesterol-modified carboxyethyl pullulan (CHCP). Cholesterol-modified pullulan (CHP) conjugate was synthesized with a similar degree of substitution of cholesterol moiety to CHCP. CHCP formed self-aggregated NPs in aqueous solution with a spherical structure and zeta potential of -19.9 ± 0.23 mV, in contrast to -1.21 ± 0.12 mV of CHP NPs. NPs could quench albumin fluorescence intensity with maximum emission intensity gradually decreasing up to a plateau at 9 to 12 h. Binding constants were 1.12 × 10(5) M(-1) and 0.70 × 10(5) M(-1) to CHP and CHCP, respectively, as determined by Stern-Volmer analysis. The complexation between HSA and NPs was a gradual process driven by hydrophobic force and inhibited by NP surface charge and shell-core structure. HSA conformation was altered by NPs with reduction of α-helical content, depending on interaction time and particle surface charges. These NPs could represent a sustained release carrier for mitoxantrone in vitro, and the bound HSA assisted in enhancing sustained drug release.
authors.affiliation: Department of Cardiovascular Diseases, First Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Tao
authors.forename: Qiufang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Kai
authors.initials: K
authors.lastname: Ling
authors.forename: Yicun
authors.initials: Y
authors.lastname: Chen
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Yang
authors.forename: Fenfei
authors.initials: F
authors.lastname: Gao
authors.forename: Ganggang
authors.initials: G
authors.lastname: Shi
mesh_terms: D002784:Cholesterol / Q000737:chemistry; D016503:Drug Delivery Systems; D005453:Fluorescence; D005936:Glucans / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D008942:Mitoxantrone; D053758:Nanoparticles; D012709:Serum Albumin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties
chemical_list: D005936:Glucans; D012709:Serum Albumin; C009109:pullulan; D002784:Cholesterol; D008942:Mitoxantrone