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A Floating Hydrogel System Capable of Generating CO2 Bubbles to Diminish Urinary Obstruction After Intravesical Instillation

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ABSTRACT

Aim

Intravesical instillation is commonly used to decrease the tumor recurrence after transurethral resection. However, most drug solutions would be eliminated from bladder after the first voiding of urine, so its clinical efficacy is limited. To overcome this obstacle, we developed a floating hydrogel system for controlled delivery of antitumor drugs.

Methods

The floating hydrogel was made of Adriamycin, thermo-sensitive polymer (Poloxamer 407) and NH4HCO3, which was liquid at low temperature while forming hydrogel at high temperature. Meanwhile, at high temperature, NH4HCO3 decomposed to produce CO2 bubbles, which helped hydrogel float in bladder without urinary obstruction.

Results

The mixture containing 45% P407 and 6% NH4HCO3 was selected as the optimal formulation. At 37°C, the mixture formed hydrogel and produced many bubbles which could be observed by B ultrasound. The vitro study showed that the antitumor drug Doxorubicin was released in a controlled manner. After the mixture was instilled into rabbit bladder, it formed hydrogel and floated in the bladder. The bladder stimuli was reduced and antitumor drugs could be released continuously in the bladder.

Conclusion

Our results suggested that the floating hydrogel was a feasible intravesical drug delivery system and may have application prospects in intravesical therapy for bladder cancer.

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REFERENCES

  1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  2. Kirkali Z, Chan T, Manoharan M, Algaba F, Busch C, Cheng L, et al. Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology. 2005;66:4–34.

    Article  PubMed  Google Scholar 

  3. Kurth K, Bouffioux C, Sylvester R, Van der Meijden A, Oosterlinck W, Brausi M. Treatment of superficial bladder tumors: achievements and needs. Eur Urol. 2000;37:1–9.

    Article  PubMed  CAS  Google Scholar 

  4. Gontero P, Cattel L, Paone TC, Milla P, Berta G, Fiorito C, et al. Pharmacokinetic study to optimize the intravesical administration of gemcitabine. BJU Int. 2010;106:1652–6.

    Article  PubMed  CAS  Google Scholar 

  5. Wientjes MG, Badalament RA, Au JL-S. Use of pharmacologic data and computer simulations to design an efficacy trial of intravesical mitomycin C therapy for superficial bladder cancer. Cancer Chemother Pharmacol. 1993;32:255–62.

    Article  PubMed  CAS  Google Scholar 

  6. Lu Z, Yeh T-K, Tsai M, Au JL-S, Wientjes MG. Paclitaxel-loaded gelatin nanoparticles for intravesical bladder cancer therapy. Clin Cancer Res. 2004;10:7677–84.

    Article  PubMed  CAS  Google Scholar 

  7. Burjak M, Bogataj M, Velnar M, Grabnar I, Mrhar A. The study of drug release from microspheres adhered on pig vesical mucosa. Int J Pharm. 2001;224:123–30.

    Article  PubMed  CAS  Google Scholar 

  8. Tyagi P, Li Z, Chancellor M, De Groat WC, Yoshimura N, Huang L. Sustained intravesical drug delivery using thermosensitive hydrogel. Pharm Res. 2004;21:832–7.

    Article  PubMed  CAS  Google Scholar 

  9. Men K, Liu W, Li L, Duan X, Wang P, Gou M, et al. Delivering instilled hydrophobic drug to the bladder by a cationic nanoparticle and thermo-sensitive hydrogel composite system. Nanoscale. 2012;4:6425–33.

    Article  PubMed  CAS  Google Scholar 

  10. Gou M, Li X, Dai M, Gong C, Wang X, Xie Y, et al. A novel injectable local hydrophobic drug delivery system: biodegradable nanoparticles in thermo-sensitive hydrogel. Int J Pharm. 2008;359:228–33.

    Article  PubMed  CAS  Google Scholar 

  11. Collado A, Chechile G, Salvador J, Vicente J. Early complications of endoscopic treatment for superficial bladder tumors. J Urol. 2000;164:1529–32.

    Article  PubMed  CAS  Google Scholar 

  12. Veyries ML, Couarraze G, Geiger S, Agnely F, Massias L, Kunzli B, et al. Controlled release of vancomycin from poloxamer 407 gels. Int J Pharm. 1999;192:183–93.

    Article  PubMed  CAS  Google Scholar 

  13. Paavola A, Kilpelainen I, Yliruusi J, Rosenberg P. Controlled release injectable liposomal gel of ibuprofen for epidural analgesia. Int J Pharm. 2000;199:85–93.

    Article  PubMed  CAS  Google Scholar 

  14. Chung HJ, Lee Y, Park TG. Thermo-sensitive and biodegradable hydrogels based on stereocomplexed Pluronic multi-block copolymers for controlled protein delivery. J Control Release. 2008;127:22–30.

    Article  PubMed  CAS  Google Scholar 

  15. Min B, Bae IY, Lee HG, Yoo S-H, Lee S. Utilization of pectin-enriched materials from apple pomace as a fat replacer in a model food system. Bioresour Technol. 2010;101:5414–8.

    Article  PubMed  CAS  Google Scholar 

  16. Yehand AC, Bai H. Comparison of ammonia and monoethanolamine solvents to reduce CO2 greenhouse gas emissions. Sci Total Environ. 1999;228:121–33.

    Article  Google Scholar 

  17. Sharmaand PK, Bhatia SR. Effect of anti-inflammatories on Pluronic® F127: micellar assembly, gelation and partitioning. Int J Pharm. 2004;278:361–77.

    Article  Google Scholar 

  18. Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm Res. 2006;23:2709–28.

    Article  PubMed  CAS  Google Scholar 

  19. Ricci E, Lunardi L, Nanclares D, Marchetti J. Sustained release of lidocaine from Poloxamer 407 gels. Int J Pharm. 2005;288:235–44.

    Article  PubMed  CAS  Google Scholar 

  20. Lin T, Wu J, Zhao X, Lian H, Yuan A, Tang X, et al. In situ floating hydrogel for intravesical delivery of adriamycin without blocking urinary tract. J Pharm Sci. 2014;103:927–36.

    Article  PubMed  CAS  Google Scholar 

  21. Wangand P, Johnston T. Kinetics of sol‐to‐gel transition for poloxamer polyols. J Appl Polym Sci. 1991;43:283–92.

    Article  Google Scholar 

  22. Alexandridisand P, Alan Hatton T. Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling. Colloids Surf A Physicochem Eng Asp. 1995;96:1–46.

    Article  Google Scholar 

  23. Zhang L, Parsons DL, Navarre C, Kompella UB. Development and in-vitro evaluation of sustained release Poloxamer 407 (P407) gel formulations of ceftiofur. J Control Release. 2002;85:73–81.

    Article  PubMed  CAS  Google Scholar 

  24. Costaand P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13:123–33.

    Article  Google Scholar 

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ACKNOWLEDGMENTS AND DISCLOSURES

This paper was supported by Research Fund for the Doctoral Program of Higher Education of China (No. 20110091120044), Natural Science Foundation of Jiangsu BK2011572 and BK2011539, National Natural Science Foundation (No. 81202474, 30973651, 81171786), Changzhou Special Project of Biotechnology and Biopharmacy (No. CE20105006) Postdoctoral Foundation (2012M521051).

Tingsheng Lin and Yifan Zhang contributed equally to the article.

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Authors and Affiliations

  1. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 22 Hankou Road, Nanjing, 210093, China

    Tingsheng Lin, Yifan Zhang, Jinhui Wu & Yiqiao Hu

  2. The Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210093, China

    Tingsheng Lin, Xiaozhi Zhao, Huibo Lian, Wei Wang & Hongqian Guo

  3. Jiangsu Key Laboratory for Nano Technology, Nanjing, 210093, China

    Jinhui Wu & Yiqiao Hu

  4. 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China

    Hongqian Guo

Authors
  1. Tingsheng Lin
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  2. Yifan Zhang
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  3. Jinhui Wu
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  4. Xiaozhi Zhao
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  5. Huibo Lian
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  6. Wei Wang
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  7. Hongqian Guo
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  8. Yiqiao Hu
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Corresponding authors

Correspondence to Jinhui Wu, Hongqian Guo or Yiqiao Hu.

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Lin, T., Zhang, Y., Wu, J. et al. A Floating Hydrogel System Capable of Generating CO2 Bubbles to Diminish Urinary Obstruction After Intravesical Instillation. Pharm Res 31, 2655–2663 (2014). https://doi.org/10.1007/s11095-014-1362-y

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  • DOI: https://doi.org/10.1007/s11095-014-1362-y

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