title: Controlled production of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) nanoparticles for targeted and sustained drug delivery.
abstract: The ability to control the size and quality of nanoparticles (NPs) during production is critical for their success as a commercial product for clinical applications. Here, we employed a statistical design of experiment approach to identify the key process variables affecting the size of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) NPs during production via the solvent evaporation method. The number of sonication cycles had a standardzed effect on NP size of 55, with sonication power at 25, and PHBHHx concentration at 27 with a combination of these variables having a lower yet significant effect on NP size (p < 0.05). The PHBHHx NPs were stable for at least 7 days with an average polydispersity index of 0.18, a zeta potential of -10 to -40 mV, and an encapsulation efficiency of 63.5 ± 2%. These data were utilized to produce a prediction graph whereby particles could be produced with sizes ranging from 90 to 205 nm with a low mean curve prediction error of 1.96% for Haperzine-A-loaded NPs. Furthermore, a range of drug encapsulates NPs were produced and showed a sustained release of the encapsulated drug. This study demonstrates the ability to control the size of drug-loaded particles by manipulation of the production variables, which will allow targeted and controlled drug release to fit a variety of applications.
authors.affiliation: Guy Hilton Research Centre, Institute of Science and Technology in Medicine, Keele University, Stoke-on-Trent, ST4 7QB, UK.
authors.forename: Thomas R J
authors.initials: TR
authors.lastname: Heathman
authors.forename: William R
authors.initials: WR
authors.lastname: Webb
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Han
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dan
authors.forename: Guo Qiang
authors.initials: GQ
authors.lastname: Chen
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Forsyth
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: El Haj
authors.forename: Zhirong R
authors.initials: ZR
authors.lastname: Zhang
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000737:chemistry*; D002208:Caproates / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods; D010316:Particle Size; D000094122:Polyhydroxybutyrates
chemical_list: D020155:3-Hydroxybutyric Acid; D002208:Caproates; D003692:Delayed-Action Preparations; C115940:poly(3-hydroxybutyrate-co-3-hydroxyhexanoate); D000094122:Polyhydroxybutyrates
keywords: DOE; biomaterials; controlled production; drug delivery systems; drug release; nanoparticle; nanotechnology; polyhydroxyalkanoates; polymeric drug carrier