Advertisement

Journal of Nanoparticle Research

, Volume 10, Issue 6, pp 1045–1052 | Cite as

Cellular uptake and radiosensitization of SR-2508 loaded PLGA nanoparticles

  • Cheng Jin
  • Ling Bai
  • Hong Wu
  • Zenghui Teng
  • Guozhen GuoEmail author
  • Jingyuan Chen
Research Paper

Abstract

SR-2508 (etanidazole), a hypoxic radiosensitizer, has potential applications in radiotherapy. The poly(d,l-lactide-co-glycolide)(PLGA) nanoparticles containing SR-2508 were prepared by w/o/w emulsification-solvent evaporation method. The physicochemical characteristics of the nanoparticles (i.e. encapsulation efficiency, particle size distribution, morphology, in vitro release) were studied. The cellular uptake of the nanoparticles for the two human tumor cell lines: human breast carcinoma cells (MCF-7) and human carcinoma cervices cells (HeLa), was evaluated by fluorescence microscopy and transmission electronic microscopy. Cell viability was measured by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical in shape with size between 90 nm and 190 nm. The encapsulation efficiency was 20.06%. The drug release pattern exhibited an initial burst followed by a plateau for over 24 h. The cellular uptake of nanoparticles was observed. Co-culture of MCF-7 and HeLa cells with SR-2508 loaded nanoparticles showed that released SR-2508 retained its bioactivity and effectively sensitized two hypoxic tumor cell lines to radiation. The radiosensitization of SR-2508 loaded nanoparticles was more significant than that of free drug.

Keywords

SR-2508 Drug delivery Nanoparticle Radiation Hypoxia Human tumor cells Radiotherapy Nanomedicine 

Notes

Acknowledgement

The authors would like to thank Dr. JY Liu (Department of Radiation Medicine, Fourth Military Medical University) for technical assistance.

References

  1. Adams GE (1981) Hypoxia-mediated drugs for radiation and chemotherapy. Cancer 48:696–709CrossRefGoogle Scholar
  2. Adams GE, Stratford IJ (1986) Hypoxia-mediated nitroheterocyclic drugs in the radio- and chemotherapy of cancer. Biochem Pharmacol 35:71–76CrossRefGoogle Scholar
  3. Astete CE, Sabliov CM (2006) Synthesis and characterization of PLGA nanoparticles. J Biomater Sci Polym Ed 17:247–289CrossRefGoogle Scholar
  4. Avgoustakis K (2004) Pegylated poly (lactide) and poly (lactide-co-glycolide) nanoparticles: preparation, properties and possible applications in drug delivery. Curr Drug Deliv 1:321–333CrossRefGoogle Scholar
  5. Bala I, Hariharan S, Kumar MN (2004) PLGA nanoparticles in drug delivery: the state of the art. Crit Rev Ther Drug Carrier Syst 21:387–422CrossRefGoogle Scholar
  6. Brigger I, Dubernet C, Couvreur P (2002) Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev 54:631–651CrossRefGoogle Scholar
  7. Brown JM (1979) Evidence for actuely hypoxic cells in mouse tumour and a possible mechanism of reoxygenation. Br J Radiol 52:650–656Google Scholar
  8. Brown JM (1982a) The mechanisms of cytotoxicity and chemosensitization of misonidazole and other nitromidazoles. Int J Radiat Oncol Biol Phys 8:675–682Google Scholar
  9. Brown JM (1982b) Clinical perspectives for the use of new hypoxic cell sensitizers. Int J Radiat Oncol Biol Phys 8:1491–1497Google Scholar
  10. Bush RS, Jenkin RDT, Allt WEC et al (1978) Definitive evidence for hypoxic cells influence in the cure in cancer therapy. Br J Cancer 37(suppl. III):302–306Google Scholar
  11. Coleman CN, Wasserman TH, Urtasun RC et al (1986) Phase I trial of the hypoxic cell radiosensitizer SR-2508: the results of the five to six week drug schedule. Int J Radiat Oncol Biol Phys 12:1105–1108Google Scholar
  12. Costantino L, Gandolfi F, Bossy-Nobs L et al (2006) Nanoparticulate drug carriers based on hybrid poly (d,l-lactide-co-glycolide)-dendron structures. Biomaterials 27:4635–4645CrossRefGoogle Scholar
  13. Desai MP, Labhasetwar V, Walter E et al (1997) The mechanism of uptake of biodegradable microparticles in CaCO-2 cells is size dependant. Pharm Res 14:1568–1573CrossRefGoogle Scholar
  14. Dische S (1985) Chemical sensitizers for hypoxic cell: a decade of experience in clinical radiotherapy. Radiother Oncol 3:97–115CrossRefGoogle Scholar
  15. Eschwege F, Sancho-Garnier H, Chassagne D et al (1997) Results of a European randomized trial of etanidazole combined with radiotherapy in head and neck carcinomas. Int J Radiat Oncol Biol Phys 39:273–274Google Scholar
  16. Gray LH, Conger AD, Ebert M et al (1953) The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 26:638–648CrossRefGoogle Scholar
  17. Howes AE (1969) An estimation of changes in the proportion and absolute numbers of hypoxic cell after irradiation of transplanted C3H mouse mammary tumors. Br J Radiol 42:441–447Google Scholar
  18. Konan YN, Gurney R, Allemann E (2002) Preparation and characterization of sterile and freeze-dried sub-200 nm nanoparticles. Int J Pharm 233:239–252CrossRefGoogle Scholar
  19. Kwon GS, Kataoka K (1995) Block copolymer micelles as longcirculating drug vehicles. Adv Drug Deliv Rev 16:295–309CrossRefGoogle Scholar
  20. Lawton CA, Coleman CN, Buzydlowski JW et al (1996) Results of a phase II trial of external beam radiation with etanidazole (SR-2508) for the treatment of locally advanced prostate cancer. Int J Radiat Oncol Biol Phys 36:673–680CrossRefGoogle Scholar
  21. Lee DJ, Cosmatos D, Marcial VA et al (1995) Results of an RTOG phase III trial (RRTOG 85 ± 27) comparing radiotherapy plus etanidazole with radiotherapy alone for locally advanced head and neck carcinomas. Int J Radiat Oncol Biol Phys 32:567–576Google Scholar
  22. Lee TH, Wang FJ, Wang CH (2002) Double-walled microspheres for the sustained release of a highly water soluble drug: characterization and irradiation studies. J Control Release 83:437–452CrossRefGoogle Scholar
  23. Moghimi SM, Porter CJH, Muir IS et al (1991) Non-phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particles size and hydrophilic coating. Biochem Biophys Res Commun 177:861–866CrossRefGoogle Scholar
  24. O’Dwyer PJ, LaCreta FP (1991) Pharmacology and clinical investigation of SR-2508 (etanidazole). In: New drugs, concepts, and results in cancer chemotherapy, pp 45–63Google Scholar
  25. Panyam J, Labhasetwar V (2003) Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 55:329–347CrossRefGoogle Scholar
  26. Panyam J, Williams D, Dash A et al (2004) Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles. J Pharm Sci 93:1804–1814CrossRefGoogle Scholar
  27. Riese NE, Buswell L, Noll L et al (1997) Pharacokinetic monitoring and dose modification of etanidazole in the RTOG 85–27 phase III head and neck trial. Int J Radiat Oncol Biol Phys 39:855–858Google Scholar
  28. Urtasun RC, Palmer M, Kinney B et al (1998) Intervention with the hypoxic tumor cell sensitizer etanidazole in the combined modality treatment of limited stage small-cell lung cancer, a one-institution study. Int J Radiat Oncol Biol Phys 40:337–342Google Scholar
  29. Wang FJ, Wang CH (2002a) Effects of fabrication conditions on the characteristics of etanidazole spray-dried microspheres. J Microencapsul 4:495–510CrossRefGoogle Scholar
  30. Wang FJ, Wang CH (2002b) Sustained release of etanidazole from spray dried microspheres prepared by non-halogenated solvents. J Control Release 81:263–280Google Scholar
  31. Wang FJ, Wang CH (2003) Etanidazole-loaded microspheres fabricated by spray-drying different poly(lactide/glycolide) polymers: effects on microsphere properties. J Biomater Sci Polym Ed 14:157–183CrossRefGoogle Scholar
  32. Yin Y, Chen D, Qiao M et al (2006) Preparation and evaluation of lectin-conjugated PLGA nanoparticles for oral delivery of thymopentin. J Control Release 116:337–345CrossRefGoogle Scholar
  33. Yuan F, Leuning M, Huang SK et al (1994) Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in human tumor xenograft. Cancer Res 54:3352–3356Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Cheng Jin
    • 1
  • Ling Bai
    • 2
  • Hong Wu
    • 3
  • Zenghui Teng
    • 4
  • Guozhen Guo
    • 1
    Email author
  • Jingyuan Chen
    • 5
  1. 1.Department of Radiation MedicineFourth Military Medical UniversityXi’anChina
  2. 2.Department of Clinical LaboratoriesXi’an Gaoxin HospitalXi’anChina
  3. 3.Department of PharmacyFourth Military Medical UniversityXi’anChina
  4. 4.Department of PharmacologyFourth Military Medical UniversityXi’anChina
  5. 5.Department of Occupational and Environmental HealthFourth Military Medical UniversityXi’anChina

Personalised recommendations