Effect of encapsulation of chloramphenicol in albumin microspheres on its in vitro transfer across the human placenta

Abstract

The possibility of reducing drug transfer across the placenta was tested in two of our previous studies. The aim of those studies was to demonstrate an alternative method of drug application during pregnancy which we think would yield a dual benefit, i.e. protecting the foetus from the harmful effects of drugs while curing the mother. The present study was planned as a continuation of the testing of the same idea and we tried to see the effect of albumin microsphere encapsulation of chloramphenicol on its transfer across the human placenta in vitro. Microspheres containing chloramphenicol were prepared according to the method previously described. The mean per cent encapsulation of chloramphenicol in albumin microspheres was found to be 42 ± 4.3 per cent (n = 5) and the mean size of the albumin microspheres was 3.08 ± 0.6 mm. In vitro stability of the drug-carrying microspheres was measured by dialysing them at 37°C for 24h., Chloramphenicol was released from the microspheres gradually leaving about 50 per cent of the entrapped drug in the microspheres after 1.5 h. About 20 per cent of the chloramphenicol was retained in the microspheres at 24 h postincubation. The persistence of the antibacterial effect of the released chloramphenicol is confirmed by antibiogramme tests. In the perfusions the initial free drug concentration was kept at 100mg/ml. When the values are expressed as the mean total (per cent) transfer of chloramphenicol which is defined as the proportion of the total drug in the maternal circulation at zero time, that subsequently appeared in the foetal circulation per gram weight of the perfused cotyledon after 60min, the calculated mean values were 0.05 ± 0.018 per cent for the encapsulated (n = 5) and 1.04 ± 0.12 per cent for the free drug (n = 6). This means that about 21 times less drug is transferred to the foetal side when it is administered in albumin microspheres. Statistical analyses (t-test) revealed that this decrease in the drug transfer is significant (p < 0.01).