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Development and characterization of bio-derived polyhydroxyalkanoate nanoparticles as a delivery system for hydrophobic photodynamic therapy agents

  • Sasivimon Pramual
  • Apinya Assavanig
  • Magnus Bergkvist
  • Carl A. Batt
  • Panya Sunintaboon
  • Kriengsak Lirdprapamongkol
  • Jisnuson Svasti
  • Nuttawee NiamsiriEmail author
Delivery Systems Original Research
Part of the following topical collections:
  1. Delivery Systems

Abstract

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.

Keywords

Drug Loading PHAs Entrapment Efficiency Drug Entrapment Efficiency Human Colon Adenocarcinoma Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

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.

References

  1. 1.
    Schuitmaker JJ, Baas P, Leengoed HLLM, Meulen FW, Star WM, Zandwijk N. Photodynamic therapy: a promising new modality for the treatment of cancer. J Photochem Photobiol B, Biol. 1996;34:3–12.CrossRefGoogle Scholar
  2. 2.
    Hopper C. Photodynamic therapy: a clinical reality in the treatment of cancer. Lancet Oncol. 2000;1:212–9.CrossRefGoogle Scholar
  3. 3.
    Brown SB, Brown EA, Walker I. The present and future role of photodynamic therapy in cancer treatment. Lancet Oncol. 2004;5:497–508.CrossRefGoogle Scholar
  4. 4.
    Hopper C, Kubler A, Lewis H, Tan IB, Putnam G. mTHPC-mediated photodynamic therapy for early oral squamous cell carcinoma. Int J Cancer. 2004;111:138–46.CrossRefGoogle Scholar
  5. 5.
    Molinari A, et al. m-THPC-mediated photodynamic therapy of malignant gliomas: assessment of a new transfection strategy. Int J Cancer. 2007;121:1149–55.CrossRefGoogle Scholar
  6. 6.
    Zimmermann A, Ritsch-Marte M, Kostron H. mTHPC-mediated photodynamic diagnosis of malignant brain tumors. Photochem Photobiol. 2001;74:611–6.CrossRefGoogle Scholar
  7. 7.
    O’Connor AE, Gallagher WM, Byrne AT. Porphyrin and nonporphyrin photosensitizers in oncology: preclinical and clinical advances in photodynamic therapy. Photochem Photobiol. 2009;85:1053–74.CrossRefGoogle Scholar
  8. 8.
    Henderson BW, Dougherty TJ. How does photodynamic therapy work? Photochem Photobiol. 1992;55:145–57.CrossRefGoogle Scholar
  9. 9.
    Berg K, et al. Porphyrin-related photosensitizers for cancer imaging and therapeutic applications. J Microsc. 2005;218:133–47.CrossRefGoogle Scholar
  10. 10.
    Kostron H, Bellnier DA, Lin CW, Swartz MR, Martuza RL. Distribution, retention, and phototoxicity of hematoporphyrin derivative in a rat glioma. J Neurosurg. 1986;64:768–74.CrossRefGoogle Scholar
  11. 11.
    Taquet JP, Frochot C, Manneville V, Barberi-Heyob M. Phthalocyanines covalently bound to biomolecules for a targeted photodynamic therapy. Curr Med Chem. 2007;14:1673–87.CrossRefGoogle Scholar
  12. 12.
    Bechet D, Couleaud P, Frochot C, Viriot ML, Guillemin F, Barberi-Heyob M. Nanoparticles as vehicles for delivery of photodynamic therapy agents. Trends Biotechnol. 2008;26:612–21.CrossRefGoogle Scholar
  13. 13.
    Pavani C, Uchoa AF, Oliveira CS, Iamamoto Y, Baptista MS. Effect of zinc insertion and hydrophobicity on the membrane interactions and PDT activity of porphyrin photosensitizers. Photochem Photobiol Sci. 2009;8:233–40.CrossRefGoogle Scholar
  14. 14.
    Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev. 2003;55:329–47.CrossRefGoogle Scholar
  15. 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. 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
  17. 17.
    Konan-Kouakou YN, Boch R, Gurny R, Allemann E. In vitro and in vivo activities of verteporfin-loaded nanoparticles. J Control Release. 2005;103:83–91.CrossRefGoogle Scholar
  18. 18.
    Zeisser-Labouebe M, Lange N, Gurny R, Delie F. Hypericin-loaded nanoparticles for the photodynamic treatment of ovarian cancer. Int J Pharm. 2006;326:174–81.CrossRefGoogle Scholar
  19. 19.
    Hu Z, Pan Y, Wang J, Chen J, Li J, Ren L. Meso-tetra (carboxyphenyl) porphyrin (TCPP) nanoparticles were internalized by SW480 cells by a clathrin-mediated endocytosis pathway to induce high photocytotoxicity. Biomed Pharmacother. 2009;63:155–64.CrossRefGoogle Scholar
  20. 20.
    Ungun B, Prud’homme RK, Budijon SJ, Shan J, Lim SF, Ju Y, Austin R. Nanofabricated upconversion nanoparticles for photodynamic therapy. Opt Express. 2009;17:80–6.CrossRefGoogle Scholar
  21. 21.
    Anderson AJ, Dawes EA. Occurrence, metabolism, metabolic role, and industrial use of bacterial polyhydroxyalkanoates. Microbiol Rev. 1990;54:450–72.Google Scholar
  22. 22.
    Lee EY, Kang SH, Choi CY. Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) by newly isolated Agrobacterium sp. SH-1 and GW-014 from structurally unrelated single carbon substrates. J Ferment Bioeng. 1995;79:328–34.CrossRefGoogle Scholar
  23. 23.
    Verlinden RAJ, Hill DJ, Kenward MA, Williams CD, Radecka I. Bacterial synthesis of biodegradable polyhydroxyalkanoates. J Appl Microbiol. 2007;102:1437–49.CrossRefGoogle Scholar
  24. 24.
    Chanprateep S. Current trends in biodegradable polyhydroxyalkanoates. J Biosci Bioeng. 2010;110:621–32.CrossRefGoogle Scholar
  25. 25.
    Duran N, Alvarenga MA, Da Silva EC, Melo PS, Marcato PD. Archives of microencapsulation of antibiotic rifampicin in poly(3-hydroxybutyrate-co-3-hydroxyvalerate). Arch Pharm Res. 2008;31:1509–16.CrossRefGoogle Scholar
  26. 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
  27. 27.
    Grillo R, et al. Controlled release system for ametryn using polymer microspheres: preparation, characterization and release kinetics in water. J Hazard Mater. 2011;186:1645–51.CrossRefGoogle Scholar
  28. 28.
    Lee J, Jung SG, Park CS, Kim HY, Batt CA, Kim YR. Tumor-specific hybrid polyhydroxybutyrate nanoparticle: surface modification of nanoparticle by enzymatically synthesized functional block copolymer. Bioorg Med Chem Lett. 2011;21:2941–4.CrossRefGoogle Scholar
  29. 29.
    Masood F, Chen P, Yasin T, Fatima N, Hasan F, Hameed A. Encapsulation of Ellipticine in poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) based nanoparticles and its in vitro application. Mater Sci Eng C Mater. 2013;33:1054–60.CrossRefGoogle Scholar
  30. 30.
    Vilos C, et al. Paclitaxel-PHBV nanoparticles and their toxicity to endometrial and primary ovarian cancer cells. Biomaterials. 2013;34:4098–108.CrossRefGoogle Scholar
  31. 31.
    Bonnett R, McGarvey DJ, Harriman A, Land EJ, Truscott TG, Winfield UJ. Photophysical properties of meso-tetraphenylporphyrin and some meso-tetra (hydroxyphenyl) porphyrins. Photochem Photobiol. 1988;48:271–6.CrossRefGoogle Scholar
  32. 32.
    Nawalany K, et al. Novel nanostructural photosensitizers for photodynamic therapy: in vitro studies. Int J Pharm. 2012;430:129–40.CrossRefGoogle Scholar
  33. 33.
    Berenbaum MC, Akande SL, Bonnett R, Kaur H, Ioannou S, White RD, Winfield UJ. meso-Tetra (hydroxyphenyl) porphyrins, a new class of potent tumour photosensitisers with favourable selectivity. Br J Cancer. 1986;54:717–25.CrossRefGoogle Scholar
  34. 34.
    Bonnett R, White RD, Winfield UJ, Berenbaum MC. Hydroporphyrins of the meso-tetra (hydroxyphenyl) porphyrin series as tumour photosensitizers. Biochem J. 1989;261:277–80.CrossRefGoogle Scholar
  35. 35.
    Gomer CJ. Preclinical examination of first and second generation photosensitizers used in photodynamic therapy. Photochem Photobiol. 1991;54:1093–107.CrossRefGoogle Scholar
  36. 36.
    Kepczynski M, Nawalany K, Kumorek M, Kobierska A, Jachimska B, Nowakowska M. Which physical and structural factors of liposome carriers control their drug-loading efficiency? Chem Phys Lipids. 2008;155:7–15.CrossRefGoogle Scholar
  37. 37.
    Shang L, Yim SC, Park HG, Chang HN. Sequential feeding of glucose and valerate in a fed-batch culture of Ralstonia eutropha for production of poly(hydroxybutyrate-co-hydroxyvalerate) with high 3-hydroxyvalerate fraction. Biotechnol Prog. 2004;20:140–4.CrossRefGoogle Scholar
  38. 38.
    Loo CY, Sudesh K. Biosynthesis and native granule characteristics of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) in Delftia acidovorans. Int J Biol Macromol. 2007;40:466–71.CrossRefGoogle Scholar
  39. 39.
    Huijberts GNM, van der Wal H, Wilkinson C, Eggink G. Gas-chromatographic analysis of poly(3-hydroxyalkanoates) in bacteria. Biotechnol Tech. 1994;8:187–92.CrossRefGoogle Scholar
  40. 40.
    Jacquel N, Lo CW, Wei YH, Wu HS, Wang SS. Isolation and purification of bacterial poly(3-hydroxyalkanoates). Biochem Eng J. 2008;39:15–27.CrossRefGoogle Scholar
  41. 41.
    de Mello VA, Ricci-Junior E. Encapsulation of naproxen in nanostructured system: structural characterization and in vitro release studies. Quim Nova. 2011;34:933–9.CrossRefGoogle Scholar
  42. 42.
    Averineni RK, et al. PLGA 50:50 nanoparticles of paclitaxel: development, in vitro anti-tumor activity in BT-549 cells and in vivo evaluation. Bull Mater Sci. 2012;35:319–26.CrossRefGoogle Scholar
  43. 43.
    Konan YN, Gurny R, Allemann E. Preparation and characterization of sterile and freeze-dried sub-200nm nanoparticles. Int J Pharm. 2002;233:239–52.CrossRefGoogle Scholar
  44. 44.
    Konan YN, Cerny R, Favet J, Berton M, Gurny R, Allemann E. Preparation and characterization of sterile sub-200 nm meso-tetra(4-hydroxylphenyl)porphyrin-loaded nanoparticles for photodynamic therapy. Eur J Pharm Biopharm. 2003;55:115–24.CrossRefGoogle Scholar
  45. 45.
    Yoshimoto AN, et al. Hedgehog pathway signaling regulates human colon carcinoma HT-29 epithelial cell line apoptosis and cytokine secretion. PLoS One. 2012;7:e45332.CrossRefGoogle Scholar
  46. 46.
    Lirdprapamongkol K, Kramb JP, Suthiphongchai T, Surarit R, Srisomsap C, Dannhardt G, Svasti J. Vanillin suppresses metastatic potential of human cancer cells through PI3K inhibition and decreases angiogenesis in vivo. J Agric Food Chem. 2009;57:3055–63.CrossRefGoogle Scholar
  47. 47.
    Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: theory to practice. Pharm Rev. 2001;53:283–318.Google Scholar
  48. 48.
    Quintanar-Guerrero D, Fessi H, Allemann E, Doelker E. Influence of stabilizing agents and preparative variables on the formation of poly(d,l-lactic acid) nanoparticles by an emulsification-diffusion technique. Int J Pharm. 1996;143:133–41.CrossRefGoogle Scholar
  49. 49.
    Poletto FS, Fiel LA, Donida B, Re MI, Guterres SS, Pohlmann AR. Controlling the size of poly(hydroxybutyrate-co-hydroxyvalerate) nanoparticles prepared by emulsification-diffusion technique using ethanol as surface agent. Colloids Surf Physicochem Eng Asp. 2008;324:105–12.CrossRefGoogle Scholar
  50. 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
  51. 51.
    Manangana T, Shawaphuna S. Quantitative extraction and determination of polyhydroxyalkanoate accumulated in Alcaligenes latus dry cells. Sci Asia. 2010;36:199–203.CrossRefGoogle Scholar
  52. 52.
    Sahoo SK, Panyam J, Prabha S, Labhasetwar V. Residual polyvinyl alcohol associated with poly (d,l-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake. J Control Release. 2002;82:105–14.CrossRefGoogle Scholar
  53. 53.
    Musumeci T, Ventura CA, Giannone I, Ruozi B, Montenegro L, Pignatello R, Puglisi G. PLA/PLGA nanoparticles for sustained release of docetaxel. Int J Pharm. 2006;325:172–9.CrossRefGoogle Scholar
  54. 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
  55. 55.
    Asrar J, Valentin HE, Berger PA, Tran M, Padgette SR, Garbow JR. Biosynthesis and properties of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) polymers. Biomacromolecules. 2002;3:1006–12.CrossRefGoogle Scholar
  56. 56.
    Prabha S, Labhasetwar V. Critical determinants in PLGA/PLA nanoparticle-mediated gene expression. Pharm Res. 2004;21:354–64.CrossRefGoogle Scholar
  57. 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
  58. 58.
    Ritger PL, Peppas NA. A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J Control Release. 1987;5:23–36.CrossRefGoogle Scholar
  59. 59.
    Siepmann J, Peppas NA. Higuchi equation: derivation, applications, use and misuse. Int J Pharm. 2011;418:6–12.CrossRefGoogle Scholar
  60. 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
  61. 61.
    Nawalany K, et al. Comparison of photodynamic efficacy of tetraarylporphyrin pegylated or encapsulated in liposomes: in vitro studies. J Photochem Photobiol B Biol. 2009;97:8–17.CrossRefGoogle Scholar
  62. 62.
    Murueva AV, Shishatskaya EI, Kuzmina AM, Volova TG, Sinskey AJ. Microparticles prepared from biodegradable polyhydroxyalkanoates as matrix for encapsulation of cytostatic drug. J Mater Sci Mater Med. 2013;24:1905–15.CrossRefGoogle Scholar
  63. 63.
    Konan YN, Berton M, Gurny R, Allemann E. Enhanced photodynamic activity of meso-tetra(4-hydroxyphenyl)porphyrin by incorporation into sub-200nm nanoparticles. Eur J Pharm Sci. 2003;18:241–9.CrossRefGoogle Scholar
  64. 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
  65. 65.
    Holland SJ, Yasin M, Tighe B. Polymers for biodegradable medical devices VII. Hydroxy butyrate-hydroxyvalerate copolymers: degradation of copolymers and their blends with polysaccharides under in vitro physiological conditions. Biomaterials. 1990;11:206–15.CrossRefGoogle Scholar
  66. 66.
    Vargas A, et al. Improved photodynamic activity of porphyrin loaded into nanoparticles: an in vivo evaluation using chick embryos. Int J Pharm. 2004;286:131–45.CrossRefGoogle Scholar
  67. 67.
    Lee DJ, et al. Multifunctional poly (lactide-co-glycolide) nanoparticles for luminescence/magnetic resonance imaging and photodynamic therapy. Int J Pharm. 2012;434:257–63.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Sasivimon Pramual
    • 1
  • Apinya Assavanig
    • 1
  • Magnus Bergkvist
    • 2
  • Carl A. Batt
    • 3
  • Panya Sunintaboon
    • 4
  • Kriengsak Lirdprapamongkol
    • 5
  • Jisnuson Svasti
    • 5
    • 6
  • Nuttawee Niamsiri
    • 1
    Email author
  1. 1.Department of Biotechnology, Faculty of ScienceMahidol UniversityBangkokThailand
  2. 2.College of Nanoscale Science and EngineeringSUNY Polytechnic InstituteAlbanyUSA
  3. 3.Department of Food ScienceCornell UniversityNew YorkUSA
  4. 4.Department of Chemistry, Faculty of ScienceMahidol UniversityBangkokThailand
  5. 5.Laboratory of BiochemistryChulabhorn Research InstituteBangkokThailand
  6. 6.Center of Excellence in Protein Structure and Function, Faculty of ScienceMahidol UniversityBangkokThailand

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