Editorial Type:
Oncology

Assessment of in vitro release of carboplatin from six carrier media

Marije Risselada Department of Clinical Sciences, College of Veterinary Medicine, Raleigh, NC 27607.

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 DVM, PhD
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Denis J. Marcellin-Little Department of Clinical Sciences, College of Veterinary Medicine, Raleigh, NC 27607.

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Kristen M. Messenger Department of Molecular Biomedical Sciences, College of Veterinary Medicine, Raleigh, NC 27607.

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Emily Griffith Department of Statistics, College of Sciences, North Carolina State University, Raleigh, NC 27607.

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Gigi S. Davidson Department of Clinical Pharmacy Services, College of Veterinary Medicine, Raleigh, NC 27607.

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Mark G. Papich Department of Molecular Biomedical Sciences, College of Veterinary Medicine, Raleigh, NC 27607.

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DOI:
https://doi.org/10.2460/ajvr.77.12.1381
Volume/Issue:
Volume 77: Issue 12
Online Publication Date:
01 Dec 2016
Restricted access
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Abstract

OBJECTIVE To investigate in vitro carboplatin release from 6 carrier media.

SAMPLE 6 carboplatin-containing carrier media.

PROCEDURES An in vitro release study was performed with 6 commercially available carrier media: a hemostatic gelatin sponge, a poloxamer copolymer gel, and 2 sizes (3 and 4.8 mm in diameter) of beads molded from each of 2 commercial calcium sulfate products. All carrier media contained 10 mg of carboplatin. Carrier media specimens were placed in 37°C PBS solution for 96 hours. Carboplatin concentrations in PBS solution were measured by use of high-performance liquid chromatography at 15 time points to calculate the amount and proportion of carboplatin released from each specimen.

RESULTS Peak release of carboplatin from the poloxamer copolymer gel and hemostatic gelatin sponge were achieved after 4 and 20 hours, respectively. Maximum release did not differ significantly between the poloxamer copolymer gel and hemostatic gelatin sponge, but both released significantly more carboplatin within 96 hours than did both of the commercial calcium sulfate products. The poloxamer copolymer gel released 99% of the carboplatin, and the hemostatic gelatin sponge released 68.5% of the carboplatin. Peak release of carboplatin from the calcium sulfate beads was not reached within 96 hours.

CONCLUSIONS AND CLINICAL RELEVANCE In this study, carboplatin release from the hemostatic gelatin sponge was incomplete. The poloxamer copolymer gel and hemostatic gelatin sponge released carboplatin rapidly in vitro, whereas calcium sulfate beads did not.

Abstract

OBJECTIVE To investigate in vitro carboplatin release from 6 carrier media.

SAMPLE 6 carboplatin-containing carrier media.

PROCEDURES An in vitro release study was performed with 6 commercially available carrier media: a hemostatic gelatin sponge, a poloxamer copolymer gel, and 2 sizes (3 and 4.8 mm in diameter) of beads molded from each of 2 commercial calcium sulfate products. All carrier media contained 10 mg of carboplatin. Carrier media specimens were placed in 37°C PBS solution for 96 hours. Carboplatin concentrations in PBS solution were measured by use of high-performance liquid chromatography at 15 time points to calculate the amount and proportion of carboplatin released from each specimen.

RESULTS Peak release of carboplatin from the poloxamer copolymer gel and hemostatic gelatin sponge were achieved after 4 and 20 hours, respectively. Maximum release did not differ significantly between the poloxamer copolymer gel and hemostatic gelatin sponge, but both released significantly more carboplatin within 96 hours than did both of the commercial calcium sulfate products. The poloxamer copolymer gel released 99% of the carboplatin, and the hemostatic gelatin sponge released 68.5% of the carboplatin. Peak release of carboplatin from the calcium sulfate beads was not reached within 96 hours.

CONCLUSIONS AND CLINICAL RELEVANCE In this study, carboplatin release from the hemostatic gelatin sponge was incomplete. The poloxamer copolymer gel and hemostatic gelatin sponge released carboplatin rapidly in vitro, whereas calcium sulfate beads did not.

Contributor Notes

Address correspondence to Dr. Risselada (marije_risselada@ncsu.edu).
Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Dec 2016

  • 1. Withrow SJ, Liptak JM, Straw RC, et al. Biodegradable cisplatin polymer in limb-sparing surgery for canine osteosarcoma. Ann Surg Oncol 2004; 11: 705–713.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 2. Mehl ML, Seguin B, Dernell WS, et al. Survival analysis of one versus two treatments of local delivery cisplatin in a biodegradable polymer for canine osteosarcoma. Vet Comp Oncol 2005; 3: 81–86.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 3. Havlicek M, Straw RS, Langova V, et al. Intra-operative cisplatin for the treatment of canine extremity soft tissue sarcomas. Vet Comp Oncol 2009; 7: 122–129.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 4. Mendel V, Simanowski HJ, Scholz HC, et al. Therapy with gentamicin-PMMA beads, gentamicin-collagen sponge, and cefazolin for experimental osteomyelitis due to Staphylococcus aureus in rats. Arch Orthop Trauma Surg 2005; 125: 363–368.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 5. Friberg Ö, Svedjeholm R, Soderquist B. Treating sternal wound infections after cardiac surgery with an implantable gentamicin-collagen sponge. JAMA 2010; 304: 2123–2124.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 6. Riegels-Nielsen P, Espersen F, Holmich LR, et al. Collagen with gentamicin for prophylaxis of postoperative infection. Staphylococcus aureus osteomyelitis studied in rabbits. Acta Orthop Scand 1995; 66: 69–72.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 7. Mathews KG, Linder KE, Davidson GS, et al. Assessment of clotrimazole gels for in vitro stability and in vivo retention in the frontal sinus of dogs. Am J Vet Res 2009; 70: 640–647.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 8. Overstreet D, McLaren A, Calara F, et al. Local gentamicin delivery from resorbable viscous hydrogels is therapeutically effective. Clin Orthop Relat Res 2015; 473: 337–347.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 9. McConoughey SJ, Howlin RP, Wiseman J, et al. Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites. J Biomed Mater Res B Appl Biomater 2015; 103: 870–877.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 10. Ramos JR, Howard RD, Pleasant RS, et al. Elution of metronidazole and gentamicin from polymethylmethacrylate beads. Vet Surg 2003; 32: 251–261.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 11. Mackey D, Varlet A, Debeaumont D. Antibiotic loaded plaster of Paris pellets: an in vitro study of a possible method of local antibiotic therapy in bone infection. Clin Orthop Relat Res 1982; 167: 263–268.

    • Search Google Scholar
    • Export Citation

  • 12. Atilla A, Boothe HW, Tollett M, et al. In vitro elution of amikacin and vancomycin from impregnated plaster of Paris beads. Vet Surg 2010; 39: 715–721.

    • Search Google Scholar
    • Export Citation

  • 13. Seddighi MR, Griffon DJ, Constable PD, et al. Effects of porcine small intestinal submucosa on elution characteristics of gentamicin-impregnated plaster of Paris. Am J Vet Res 2007; 68: 171–177.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 14. Farnsworth KD, White NA II, Robertson J. The effect of implanting gentamicin-impregnated polymethylmethacrylate beads in the tarsocrural joint of the horse. Vet Surg 2001; 30: 126–131.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 15. Sonoda A, Nitta N, Ohta S, et al. Controlled release and antitumor effect of pluronic F127 mixed with cisplatin in a rabbit model. Cardiovasc Intervent Radiol 2010; 33: 135–142.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 16. Lee SH, Lee JE, Baek WY, et al. Regional delivery of vancomycin using pluronic F-127 to inhibit methicillin resistant Staphylococcus aureus (MRSA) growth in chronic otitis media in vitro and in vivo. J Control Release 2004; 96: 1–7.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 17. Correll JT, Prentice HR, Wise EC. Biologic investigations of a new absorbable sponge. Surg Gynecol Obstet 1945; 181: 585–589.

  • 18. MacDonald SA, Mathews WH. Further studies of gelfoam in kidney wounds; the effect of urinary wetting. Can Med Assoc J 1948; 58: 118–121.

    • Search Google Scholar
    • Export Citation

  • 19. Jenkins HP, Janda R. Studies on the use of gelatin sponge or foam as an hemostatic agent in experimental liver resections and injuries to large veins. Ann Surg 1946; 124: 952–961.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 20. Hsu YH, Chen DW, Tai CD, et al. Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies. Int J Nanomedicine 2014; 9: 4347–4355.

    • Search Google Scholar
    • Export Citation

  • 21. Pohlen U, Rieger H, Meyer BT, et al. Chemoembolization of lung metastases—pharmacokinetic behaviour of carboplatin in a rat model. Anticancer Res 2007; 27: 809–815.

    • Search Google Scholar
    • Export Citation

  • 22. Ham K, Griffon D, Seddighi M, et al. Clinical application of tobramycin-impregnated calcium sulfate beads in six dogs (2002–2004). J Am Anim Hosp Assoc 2008; 44:320–326.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 23. United States Pharmacopeia. General chapter: pharmaceutical compounding—sterile preparations. United States Pharmacopeia 39—National Formulary 34. Rockville, Md: US Pharmacopeial Convention Inc, 2016;626–670.

    • Search Google Scholar
    • Export Citation

  • 24. United States Pharmacopeia. General chapter <1225>: validation of compendial procedures. United States Pharmacopeia 37. Rockville, Md: United States Pharmacopeial Convention Inc, 2014;1–5. Available at: hmc.usp.org/sites/default/files/documents/HMC/GCs-Pdfs/c1225.pdf. Accessed Jul 5, 2016.

    • Search Google Scholar
    • Export Citation

  • 25. Nanjwade BK, Singh J, Parikh KA, et al. Preparation and evaluation of carboplatin biodegradable polymeric nanoparticles. Int J Pharm 2010; 385: 176–180.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 26. Karanam V, Marslin G, Krishnamoorthy B, et al. Poly (varepsilon-caprolactone) nanoparticles of carboplatin: preparation, characterization and in vitro cytotoxicity evaluation in U-87 MG cell lines. Colloids Surf B Biointerfaces 2015; 130: 48–52.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 27. Nisha MJ, Pramod KS. Cross-linked nanoparticles in cytarabine: encapsulation, storage and in-vitro release. Afr J Pharm Pharmacol 2007; 1: 010–013.

    • Search Google Scholar
    • Export Citation

  • 28. Chen Y, Zhang W, Huang Y, et al. Pluronic-based functional polymeric mixed micelles for co-delivery of doxorubicin and paclitaxel to multidrug resistant tumor. Int J Pharm 2015; 488: 44–58.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 29. Veyries ML, Couarraze G, Geiger S, et al. Controlled release of vancomycin from poloxamer 407 gels. Int J Pharm 1999; 192: 183–193.

  • 30. Hsu SH, Leu YL, Hu JW, et al. Physicochemical characterization and drug release of thermosensitive hydrogels composed of a hyaluronic acid/Pluronic F127 graft. Chem Pharm Bull (Tokyo) 2009; 57: 453–458.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 31. van der Vijgh WJ. Clinical pharmacokinetics of carboplatin. Clin Pharmacokinet 1991; 21: 242–261.

  • 32. Oguri S, Sakakibara T, Mase H, et al. Clinical pharmacokinetics of carboplatin. J Clin Pharmacol 1988; 28: 208–215.

  • 33. Roberts R, McConoughey SJ, Calhoun JH. Size and composition of synthetic calcium sulfate beads influence dissolution and elution rates in vitro. J Biomed Mater Res B Appl Biomater 2014; 102: 667–673.

    • Crossref
    • Search Google Scholar
    • Export Citation

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