Chromatographic studies of mitomycin C degradation in albumin microspheres.
Serum albumins and polylactic acid (PLA) have been used as bioerodable polymers in the preparation of drug-containing microspheres for parenteral drug delivery. The albumin microsphere may be prepared via either chemical cross-linking or heat denaturation of the protein. Heat-denatured albumin microspheres containing mitomycin C (MMC) have been used in pre-clinical and clinical investigations. Due to the high reactivity of MMC as a bifunctional alkylating agent, a study on the stability of MMC in the albumin and PLA microspheres has been carried out using a high-performance liquid chromatographic (HPLC) method. Human serum albumin (HSA) microspheres were prepared using an emulsion method via either heat denaturation at 120 or 170 degrees C or the use of 0.5 M biacetyl as a cross-linking agent. The PLA microspheres were prepared by an emulsion method at 55 degrees C. HPLC analysis of the HSA microspheres showed that about 37% of MMC was converted to 2,7-diaminomitosene derivatives in microspheres prepared by heat denaturation at 120 degrees C. The degradation increased to 82% when the microspheres were prepared with a denaturation temperature of 170 degrees C. The use of biacetyl as a cross-linking agent in the preparation of HSA microspheres resulted in a complete degradation of the incorporated MMC. Biacetyl was found to interact with MMC leading to the formation of 7-aminomitosene derivatives. In contrast to the albumin system, MMC may be incorporated into PLA microspheres without degradation.
Mehta
R C
RC
School of Pharmacy, West Virginia University, Morgantown 26506.
Hogan
T F
TF
Mardmomen
S
S
Ma
J K
JK
D000418:Albumins / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D007536:Isomerism; D007773:Lactates / Q000032:analysis; D019344:Lactic Acid; D008863:Microspheres; D016685:Mitomycin; D008937:Mitomycins / Q000032:analysis*; D011091:Polyesters; D011108:Polymers / Q000032:analysis; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
D000418:Albumins; D007773:Lactates; D008937:Mitomycins; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D016685:Mitomycin