INDICATIONS: Equine Sarcoids
PHARMACOLOGY:
Release Profile
The solubility of Cisplatin is 1 mg/ml. Hence, 99% of the Cisplatin is suspended in the MIII Cisplatin Beads as small solid particles (≤ 63 micron).
According to Fick’s law the diffusion rate is given by Rate = AD(d[m]/dx) where d[M]/dx is the concentration gradient of the medicinal at the boundary of the bead.
We can express D as a variation of the Stokes-Einstein Equation:
D = kS/vMw
In which k is a constant, S is the solubility of the medicinal, v is the viscosity, and Mw is the molecular weight of the medicinal. The relative low solubility of the Cisplatin would contribute to prolonged release. The presence of the polymer potentially slows the release in two ways. First, the viscosity, v, is raised and the Cisplatin effective molecular weight would be raised by ionic complexation with the polymer.
An In Vitro release profile shown below.
In Vitro Release Profile
When beads are placed subcutaneously the drug travels 1.5 cm radius (Figure 3). The release profile and activity of Cisplatin may also be influenced by the following equilibria:
Pt(NH2)(Cl2) + H20 = Pt(NH2)(Cl)(H2O)+ + Cl - (1)
Pt(NH2)(Cl)(H2O)+ = Pt(NH2)(Cl)(OH) + H+ (2)
In the cell, the chloride concentration is much lower than that in the interstitial fluid, which would favor reaction (1). In other words, the neutral Cisplatin enters the cell and the aquation reaction occurs which produces a cationic species (reaction (2)) which has an affinity for DNA (negatively charged).
In Vivo Release Profile. Matrix IIITM Cisplatin Beads (3 mm) Placed s.c.
Mean Concentration versus Distance from Bead Boundary.
Stability of MIII Cisplatin Beads
Crystalline Cisplatin is stable indefinitely in the solid state at ambient temperature in the dark. Not surprising, we have tested the stability of MIII Cisplatin Beads and have shown no significant change after one year. Chemical criteria and biological activity were assessed. We are confident that the product is stable for much longer than one year.