Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2005 March; 6(1): E108–E114.
Published online 2005 September 20. doi:  10.1208/pt060117
PMCID: PMC2750418

Spray-dried poly(D,L-lactide) microspheres containing carboplatin for veterinary use: In vitro and in vivo studies


The aim of this study was the development of a veterinary dosage form constituted by injectable biodegradable microspheres designed for the subcutaneous release of carboplatin, a chemotherapeutic drug. Poly(D,L-lactide) (PDLLA) microspheres were prepared by an emulsification/spray-drying method, using the drug-to-polymer weight ratios 1[ratio]9 and 1[ratio]5; blank microspheres (1% w/v) were prepared as a comparison. Microparticles were characterized in terms of morphology, encapsulation efficiency, and in vitro drug release behavior. In vivo tests were conducted on rats by subcutaneous injection of microsphere aqueous suspensions. Levels of carboplatin were evaluated both in the skin and in serum. The microparticles obtained had a spherical shape; particle size ranged from 5 to 7 μm, dependent on drug loading. Microspheres were able to control the in vitro release of the drug: approximately 90% to 100% of the carboplatin was released over 30 days. In vivo results showed that the microspheres were able to release high drug amounts locally, and sustained serum levels of drug were also achieved. Based on these results, carboplatin-loaded PDLLA microspheres may be useful for local delivery of the antineoplastic drug to the tumor, avoiding tumor recurrence in small animals, and may decrease the formation of distant metastases.

Keywords: local chemotherapy, companion animals, poly(D,L-lactide), carboplatin, microspheres, spray-drying

Full Text

The Full Text of this article is available as a PDF (500K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Bergman PJ, MacEwen G, Kurzman ID, et al. Amputation and carboplatin for treatment of dogs with osteosarcoma: 48 cases (1991 to 1993) J Vet Intern Med. 1996;10:76–81. [PubMed]
2. Lana SE, Dernell WE, LaRue SM, et al. Slow release cisplatin combined with radiation for the treatment of canine nasal tumours. Vet Radiol Ultrasound. 1997;38:474–478. doi: 10.1111/j.1740-8261.1997.tb00875.x. [PubMed] [Cross Ref]
3. Withrow SJ. Surgical oncology. In: Withrow SJ, MacEwen EG, editors. Small animal clinical oncology. 3rd ed. Philadelphia: WB Saunders; 2001. pp. 70–75.
4. Goldberg EP, Hadba AR, Almond BA, Marotta JS. Intratumoral cancer chemotherapy and immunotherapy:opportunities for nonsystemic preoperative drug delivery. J Pharm Pharmacol. 2002;54:159–180. doi: 10.1211/0022357021778268. [PubMed] [Cross Ref]
5. Utsuki T, Brem H, Pitha J, et al. Potentiation of anticancer effects of microencapsulated carboplatin by hydroxypropyl α-cyclodextrin. J Control Release. 1996;40:251–260. doi: 10.1016/0168-3659(95)00192-1. [Cross Ref]
6. Chen W, Lu DR. Carboplatin-loaded PLGA microspheres for intracerebral injection: formulation and characterization. J Microencapsul. 1999;16:551–563. doi: 10.1080/026520499288753. [PubMed] [Cross Ref]
7. Emerich DF, Winn SR, Hu Y, et al. Injectable chemotherapeutic microspheres and glioma I: Enhanced survival following implantation into the cavity wall of debulked tumours. Pharm Res. 2000;17:767–765. doi: 10.1023/A:1007576405039. [PubMed] [Cross Ref]
8. Emerich DF, Winn SR, Hu Y, et al. Injectable chemotherapeutic microspheres and glioma II: Enhanced survival following implantation into deep inoperable tumours. Pharm Res. 2000;17:776–781. doi: 10.1023/A:1007591721877. [PubMed] [Cross Ref]
9. Ehrhart N, Dernell WE, Ehrhart EJ, et al. Effects of a controlled-release cisplatin delivery system used after resection of mammary carcinoma in mice. J Am Vet Med Assoc. 1999;60:1347–1351. [PubMed]
10. Orenberg EK, Luck EE, Brown DM, Mitchell BE, et al. Implant delivery system: intralesional delivery of chemotherapeutic agents for treatment of spontaneous skin tumors in veterinary patients. Clin Dermatol. 1991;9:561–568. doi: 10.1016/0738-081X(91)90085-Y. [PubMed] [Cross Ref]
11. Orenberg EK, Miller BH, Greenway HT, et al. The effect of intralesional 5-fluorouracil therapeutic implant (MPI 5003) for treatment of basal cell carcinoma. J Am Acad Dermatol. 1992;27:723–728. doi: 10.1016/0190-9622(92)70245-B. [PubMed] [Cross Ref]
12. Théon AP, Pascoe JR, Carlson GP, Krag DN. Intratumoral chemotherapy with cisplatin in oily emulsion for treatment of tumours in horses. J Am Vet Med Assoc. 1993;202:261–267. [PubMed]
13. Théon AP, Pascoe JR, Galuppo LD, Fisher PE, Griffey SM, Madigan JE. Prospective randomised comparison of perioperative versus postoperative intratumoral administration of cisplatin for treatment of cutaneous of tumours in horses. J Am Vet Med Assoc. 1999;215:1655–60. [PubMed]
14. Théon AP, Vechten MK, Madewell BR. Intratumoral administration of carboplatin for treatment of squamous cell carcinomas of the nasal plane in cats. J Am Vet Med Assoc. 1996;57:205–10. [PubMed]
15. Kubo T, Sugita T, Shimose S, Nitta Y, Ikuta Y, Murakami T. Targeted systemic chemotherapy using magnetic liposomes with incorporated adriamicin for osteosarcoma in hamsters. Int J Oncol. 2001;18:121–125. [PubMed]
16. Menei P, Venier MC, Gamelin E, et al. Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of glioblastoma: a pilot study. Cancer. 1999;86:325–330. doi: 10.1002/(SICI)1097-0142(19990715)86:2<325::AID-CNCR17>3.0.CO;2-S. [PubMed] [Cross Ref]
17. Pohlen U, Berger G, Binnenhei M, Reszka R, Buhr HJ. Increased carboplatin concentration in liver tumors through temporary flow retardation with starch microspheres (Spherex) and gelatin powder (Gelfoam): An experimental study in liver tumor-bearing rabbits. J Surg Res. 2000;92:165–170. doi: 10.1006/jsre.2000.5856. [PubMed] [Cross Ref]
18. Okada H, Toguchi H. Biodegradable microspheres in drug delivery. Crit Rev Ther Drug Carrier Syst. 1995;12:1–99. [PubMed]
19. Fu YJ, Mi FL, Wong TB, Shyu SS. Characteristic and controlled release of anticancer drug loaded poly(D,L-lactide) microparticles prepared by spray drying technique. J Microencapsul. 2001;18:733–747. doi: 10.1080/02652040010055649. [PubMed] [Cross Ref]
20. Shenoy DB, D'Souza RJ, Udupa N. Poly(DL-lactide-co-glycolide) microporous microsphere-based depot formulation of a peptide-like antineoplastic agent. J Microencapsul. 2002;19:523–535. doi: 10.1080/02652040210141084. [PubMed] [Cross Ref]
21. Zhu KJ, Zhang JX, Wang C, Yasuda H, Ichimaru A, Yamamoto K. Preparation and in vitro release behavior of 5-fluorouracil-loaded microspheres based on poly (L-lactide) and its carbonate copolymers. J Microencapsul. 2003;20:731–743. doi: 10.1080/02652040310001600785. [PubMed] [Cross Ref]
22. Anderson JM, Matthew SS. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev. 1997;28:2–24. doi: 10.1016/S0169-409X(97)00048-3. [PubMed] [Cross Ref]
23. Page RL, McEntee M, George SL, et al. Pharmacokinetic and phase 1 evaluation of carboplatin in dogs. J Vet Intern Med. 1993;7:235–240. [PubMed]
24. Moore MJ, Erlichman C. Pharmacology of anticancer drugs. In: Tannock IF, Hill RP, editors. The Basic Science of Oncology. 3rd ed. New York: McGraw-Hill Health Professions Division NY; 1998. pp. 370–391.
25. Ike O, Shimizu Y, Wada R, Hyon SH, Ikada Y. Controlled cisplatin delivery system using poly(D,L-lactic acid) Biomaterials. 1992;13:230–234. doi: 10.1016/0142-9612(92)90189-U. [PubMed] [Cross Ref]
26. Boisdron-Celle M, Menei P, Benoit JP. Preparation and characterization of 5-fluorouracil-loaded microparticles as biodegradable anticancer drug carriers. J Pharm Pharmacol. 1995;47:108–114. [PubMed]
27. Dubey RR, Parikh JR, Parikh RR. Effect of heating temperature and time on pharmaceutical characteristics of albumin microspheres containing 5-fluorouracil. AAPS PharmSciTech. 2003;4:E4–E4. doi: 10.1208/pt040104. [PMC free article] [PubMed] [Cross Ref]
28. Fu YJ, Shyu SS, Su FH, Yu PC. Development of biodegradable co-poly(D,L-lactic/glycolic acid) microspheres for the controlled release of 5-FU by the spray drying method colloids and surfaces. B Biointerfaces. 2002;25:269–279. doi: 10.1016/S0927-7765(01)00205-3. [Cross Ref]
29. Ozalp Y, Özdemir N, Kocagöz S, Hasirci V. Controlled release of Vancomycin from biodegradable microcapsules. J Microencapsul. 2001;18:89–110. doi: 10.1080/026520401750038638. [PubMed] [Cross Ref]
30. Parikh RH, Parikh JR, Dubey RR, Soni HN, Kapadia KN. Poly(D,L-lactide-co-glycolide) microspheres containing 5-fluorouracil: optimization of process parameters. AAPS PharmSciTech. 2003;4:E13–E13. doi: 10.1208/pt040213. [PMC free article] [PubMed] [Cross Ref]
31. Giunchedi P, Conte U. Spray-drying as a preparation method of microparticulate drug delivery systems: an overview. STP Pharma Sciences. 1995;5:276–290.
32. Gavini E, Sanna V, Juliano C, Giunchedi P. Compressed biodegradable matrices of spray-dried PLGA microspheres for the modified release of Ketoprofen. J Microencapsul. 2003;20:193–201. doi: 10.1080/0265204021000022752. [PubMed] [Cross Ref]
33. Giunchedi P, Gavini E, Bonacucina G, Palmieri GF. Tabletted polylactide microspheres prepared by a w/o emulsion-spray drying method. J Microencapsul. 2000;17:711–720. doi: 10.1080/02652040050161701. [PubMed] [Cross Ref]
34. Gavini E, Chetoni P, Cossu M, Alvarez MG, Saettone MF, Giunchedi P. PLGA microspheres for the ocular delivery of a peptide drug: vancomycin. Emulsification/spray-drying as preparation method; in vitro/in vivo studies. Eur J Pharm Biopharm. 2004;57:207–212. doi: 10.1016/j.ejpb.2003.10.018. [PubMed] [Cross Ref]
35. Giunchedi P, Conti B, Puglisi G, Genta I, Conte U. Emulsion spray-drying for the preparation of albumin loaded PLGA microspheres. Drug Dev Ind Pharm. 2001;27:745–750. doi: 10.1081/DDC-100107331. [PubMed] [Cross Ref]
36. Edmundson IC. In: Advances in Pharmaceutical Sciences. Bean HS, Carless JE, Beckett AH, editors. New York, NY: Academic Press; 1967.

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists