Effects of light on metalloporphyrin-treated newborn mice

Abstract

The use of polymeric particulate delivery systems can improve the stability and enhance intestinal absorption of ZnPP, while retaining HO inhibitory potency without photosensitising effects, and thus is potentially useful in treating neonatal hyperbilirubinemia.

Inhibition of heme oxygenase activity using a microparticle formulation of zinc protoporphyrin in an acute hemolytic newborn mouse model

“…In addition, ZnPP-Lipid had no inhibitory effect on brain, a nontarget organ, consistent with it not crossing the blood/brain barrier at those doses. In regards to photosensitivity, we have previously shown that even at a dose of 60 µmol/kg BW, ZnPP-Lipid (and the lipid vehicle alone) was not phototoxic to newborn mice exposed to fluorescent light (21). Furthermore, Maines have shown that ZnPP does not alter the other enzymatic activities, such as δ-aminolevulinate synthetase and cytochrome P-450, in the rat spleen and liver (7).…”

“…We first determined the peak inhibitory potency of ZnPPLipid in 4-d-old mice, by measuring liver HO activity at 1.5, 3, 6, and 12 h after IG administration of 30 µmol/kg body weight (BW) of ZnPP-Lipid, a dose we previously showed that significantly inhibits native liver HO activity in mice (21). We found that liver HO activity was significantly inhibited to 69 ± 6% (215 ± 19 pmol/h/mg fresh weight (FW), P < 0.01) and 73 ± 12% (229 ± 36 pmol/h/mg FW, P < 0.01) of control levels at 3 and 6 h, respectively, after ZnPP-Lipid administration (Figure 1).…”

“…We chose to use these lipid microparticles because they are already approved by the FDA for use in premature infants as components of synthetic surfactants (21).…”

“…A stock solution of 4 mmol/l ZnPP-Lipid (containing DPPC and DSPC) was prepared as previously described (21). Briefly, 6.26 mg of ZnPP-Lipid was dissolved in 250 µl NaCl and vigorously vortexed just prior to administration.…”

“…To allow oral bioavailability and enhance gastric passage and intestinal absorption of ZnPP, we created a lipid-based formulation of ZnPP (ZnPP-Lipid) and found that it has sufficient potency in inhibiting liver and spleen HO activity in vitro and after intragastric (IG) administration, and most importantly, is neither photo-nor chemically toxic (21).…”