Development and characterization of bio-derived polyhydroxyalkanoate nanoparticles as a delivery system for hydrophobic photodynamic therapy agents
- 647 Downloads
In this study, we developed and investigated nanoparticles of biologically-derived, biodegradable polyhydroxyalkanoates (PHAs) as carriers of a hydrophobic photosensitizer, 5,10,15,20-Tetrakis(4-hydroxy-phenyl)-21H, 23H-porphine (pTHPP) for photodynamic therapy (PDT). Three PHA variants; polyhydroxybutyrate, poly(hydroxybutyrate-co-hydroxyvalerate) or P(HB-HV) with 12 and 50 % HV were used to formulate pTHPP-loaded PHA nanoparticles by an emulsification-diffusion method, where we compared two different poly(vinyl alcohol) (PVA) stabilizers. The nanoparticles exhibited nano-scale spherical morphology under TEM and hydrodynamic diameters ranging from 169.0 to 211.2 nm with narrow size distribution. The amount of drug loaded and the drug entrapment efficiency were also investigated. The in vitro photocytotoxicity was evaluated using human colon adenocarcinoma cell line HT-29 and revealed time and concentration dependent cell death, consistent with a gradual release pattern of pTHPP over 24 h. This study is the first demonstration using bacterially derived P(HB-HV) copolymers for nanoparticle delivery of a hydrophobic photosensitizer drug and their potential application in PDT.
KeywordsDrug Loading PHAs Entrapment Efficiency Drug Entrapment Efficiency Human Colon Adenocarcinoma Cell Line
This work was supported by Thailand Research Fund (TRF) - MRG5380110 in cooperation with Office of the Higher Education Commission, Science Achievement Scholarship of Thailand (SAST) and Faculty of Science, Mahidol University.
- 15.Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986;46:6387–92.Google Scholar
- 16.Yuan F, Dellian M, Fukumura D, Leunig M, Berk DA, Torchilin VP, Jain RK. Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. Cancer Res. 1995;55:3752–6.Google Scholar
- 21.Anderson AJ, Dawes EA. Occurrence, metabolism, metabolic role, and industrial use of bacterial polyhydroxyalkanoates. Microbiol Rev. 1990;54:450–72.Google Scholar
- 26.Vilos C, Constandil L, Herrera N, Solar P, Escobar-Fica J, Velasquez L. Ceftiofur-loaded PHBV microparticles: a potential formulation for a long-acting antibiotic to treat animal infections. Electron J Biotechnol. 2012;15:1–13.Google Scholar
- 47.Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: theory to practice. Pharm Rev. 2001;53:283–318.Google Scholar
- 50.Shaffie KA, Moustafa AB, Saleh NH, Nasr HE. Effect of polyvinyl alcohol of different molecular weights as protective colloids on the kinetics of the emulsion polymerization of vinyl acetate. J Am Sci. 2010;6:1202–12.Google Scholar
- 54.Choi GG, Kim HW, Rhee YH. Enzymatic and non-enzymatic degradation of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolyesters produced by Alcaligenes sp. MT-16. J Microbiol. 2004;42:346–52.Google Scholar
- 57.Zunszain PA, Ghuman J, Komatsu T, Tsuchida E, Curry S. Crystal structural analysis of human serum albumin complexed with hemin and fatty acid. BMC Struct Biol. 2003;7:3–6.Google Scholar
- 60.Bhosale UV, Devi K, Choudhary S. Development and in vitro-in vivo evaluation of oral drug delivery system of acyclovir loaded PLGA nanoparticles. Int J Drug Deliv. 2013;5:331–43.Google Scholar
- 64.Pouton CW, Majid MIA, Natarianni LJ. Degradation of polyhydroxbutyrate and related copolymers. Proc Int Symp Control Release Bioact Mater. 1988;15:181–3.Google Scholar