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AAPS PharmSciTech. 2000 December; 1(4): 49–54.
Published online 2000 November 10. doi:  10.1208/pt010432
PMCID: PMC2750456

Effect of isopropyl myristic acid ester on the physical characteristics and in vitro release of etoposide from PLGA microspheres


The purpose of this paper was to study the effect of the isopropyl myristic acid ester (IPM) on the physicochemical characteristics of etoposide-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres-specifically, the effects on the size and drug loading of the microspheres, the polymer matrix and surface morphology, and the release of etoposide from the microspheres. The experiment was structured to examine 2 IPM concentrations (25% and 50%) and 1 control (no IPM) at 2 different etoposide-loading percentages (10% and 5%). The microspheres were prepared using a single-emulsion solvent-extraction procedure. Samples from each batch of microspheres were then analyzed for size distribution. drug-loading efficiency, surface characteristics, in vitro release, and in vitro microsphere degradation. The incorporation of 50% IPM significantly increased (P<05) the size of the microspheres when compared with the control and 25% IPM microspheres. However, incorporation of 25% or 50% IPM did not change (P>.05) the drug-loading efficiency in comparison with the microspheres prepared without IPM. The microspheres containing 50% IPM were shown to significantly increase (P<.05) the release of etoposide from the microspheres at both etoposide concentrations. The microspheres prepared incorporating 25% IPM and 5% etoposide increased the in vitro release (P<.05) in comparison with the microspheres prepared without IPM. The 5% etoposide-PLGA microspheres showed a smooth, nonporous surface that changed to a dimpled. nonporous surface after addition of 25% IPM. During the in vitro degradation study, the IPM-containing microspheres slowly became porous but retained their structural integrity throughout the experiment.

KeyWords: Etoposide, PLGA microspheres, Isopropyl myristic acid ester, In vitro release, Scanning electron microscopy

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Gupta PK. Drug targeting in cancer chemotherapy: A clinical perspectives. J. Pharm Sci. 1990;79:457–465.
2. Burger JJ, Tomlinson E, Mulder EMA, McVie JG. Albumin microspheres for intra-arterial tumor targeting. I. Pharmaceutical aspects. Int J Pharm. 1985;23:333–344. doi: 10.1016/0378-5173(85)90160-7. [Cross Ref]
3. Schaefer M, Singh J. Etoposide microspheres for targeting to the lung. Proc. Int Symp Control Rel Bioact. Mater. 1998;25:441–442.
4. Tripathi KP, Singh J. Aminophylline targeting to lung optimization of the size and drug loading of albumin microspheres. J Microencapsulation. 1992;9:229–235. doi: 10.3109/02652049109021239. [PubMed] [Cross Ref]
5. Kanke M, Simmons GH, Weiss DL, Bivins BA, DeLuca PP. Clearance of 141 Ce-labelled microspheres in specific organs following intravenous and intra-arterials administration in beagle dogs. J Pharm Sci. 1980;69:755–762. doi: 10.1002/jps.2600690703. [PubMed] [Cross Ref]
6. Illum L, David SS. Targeting of colloidal particles to the bone marrow. Life Sci. 1987;40:1553–1560. doi: 10.1016/0024-3205(87)90120-2. [PubMed] [Cross Ref]
7. Guiot P, Couvreur M. Polymeric Nanoparticles and Microspheres. Boca Raton, FL: CRC Press; 1986.
8. David SS, Hunneyball IM, Illum L, Ratcliffe JH, Smith A, Wilson CG. Recent advances in the use of microspheres for targeted therapy. Drugs Exp Clin Res. 1985;9:633–640. [PubMed]
9. David SS, Illum L, McVie JG, Tomlinson E. Microspheres and Drug Therapy. New York, NY: Elsevier; 1984.
10. Hande KR. Etoposide: four decades of development of a topoisomerase II inhibitor. Eur J Cancer. 1998;34:1514–1521. doi: 10.1016/S0959-8049(98)00228-7. [PubMed] [Cross Ref]
11. Slevin M. The clinical pharmacology of etoposide. Cancer. 1991;67:31–39. doi: 10.1002/1097-0142(19910101)67:1+<319::AID-CNCR2820671319>3.0.CO;2-D. [Cross Ref]
12. O'Dwyer P, Leyland-Jones B, Alonso MT, Marsoni S, Wittes RE. Etoposide: current status of an active anticancer drug. N Eng J Med. 1985;312:692–698. doi: 10.1056/NEJM198503143121106. [PubMed] [Cross Ref]
13. Wolf SN, Grosh WW, Prater K, et al. In vitro pharmacodynamic evaluation of VP-16213 and implications for chemotherapy. Cancer Chemother Pharmacol. 1987;19:246–249. [PubMed]
14. Lewis DD. Controlled release of bioactive agents from lactide/glycolide polymers. In: Chasin M, Langer R, editors. Biodegradable Polymers as Drug Delivery Systems. New York, NY: Marcel Dekker; 1990. pp. 1–41.
15. Jain R, Navnit HS, Mailick AW, Rhodes CT. Controlled delivery by biodegradable poly(ester) devices: different preparative approaches. Drug Dev Ind Pharm. 1998;24:703–727. doi: 10.3109/03639049809082719. [PubMed] [Cross Ref]
16. Kostanski JW, DeLuca PP. A novel in vitro release technique for peptide-containing biodegradable microspheres, PharmSciTech. 2000; 1(1) Article 4. [PMC free article] [PubMed]
17. Ravivarapu HB, Moyer KL, Dunn RL. Sustained activity and release of leuprolide acetate from an in situ forming polymeric implants, PharmSciTech 2000;1(1) Article 1. [PMC free article] [PubMed]
18. Kostanaski JW, Dani BA, Reynold G-A, Bowers CY, DeLuca PP. Evaluation of Orntide microspheres in rat animal model and correlation to in vitro release profiles, {jtPharmSciTech.} {dy2000};{vn1}({sn4}) Article 27 [PMC free article] [PubMed]
19. Gebrekidan S, Woo BH, DeLuca PP. Formulation and in vitro transfection efficiency of poly (d, 1-lactide-co-glycolide) microspheres containing plasmid DNA for gene delivery, PharmSciTech. 2000;1(4) Article 28. [PMC free article] [PubMed]
20. Park TG. Degradation of poly(lactic-co-glycolic acid) microspheres: effect of co-polymer composition. Biomaterials. 1995;16:1123–1130. doi: 10.1016/0142-9612(95)93575-X. [PubMed] [Cross Ref]
21. Sato H, Wang YM, Adachi I, Horikoshi I. Pharmacokinetic study of taxol-loaded poly(lactic-co-glycolic acid) microspheres containing isopropyl myristate after targeted delivery to the lung in mice. Biol Pharm Bull. 1996;19:1596–1601. [PubMed]
22. Wang YW, Sato H, Adachi I, Horikoshi I. Preparation and characterization of poly(lactic-co-glycolic acid) microspheres for targeted delivery of a novel anticancer agent, taxol. Chem Pharm Bull (Tokyo) 1996;44:1935–1940. [PubMed]
23. Juni K, Ogata J, Matsui N, Kubota M, Nakano M. Modification of the release rate of aclarabicin from polylactic acid microspheres. Chem Pharm Bull (Tokyo) 1985;33:1734–1738. [PubMed]
24. Chow D, Shah J. Stability-indicating high performance liquid chromatography of etoposide at various pH conditions using a reversed-phase octyl column. J Chromatogr. 1987;396:217–223. doi: 10.1016/S0021-9673(01)94059-2. [PubMed] [Cross Ref]

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