Effect Of Transdermal Liniment Of Lomefloxacin With Laurocapram On Epidermal Morphology Of Piglet And Mouse Skin

OBJECTIVE: The transdermal liniment of lomefloxacin with Laurocapram (Azone) is a new type of transdermal absorbent used for veterinary clinical medication. It has been shown many advantages in the treatment and control of some bacterial infections of animals, with its favorable pharmacokinetic characteristics. In order to clarify the mechanism of action of Azone in this liniment, the epidermal morphologic changes of skin in piglet and mouse were studied in this paper.METHODS: 12 male piglets of 10-12 days old and 35 KM male mice were randomly divided into 8 and 7 groups respectively, according to the design of group of random units. Except one group as control, the rest groups were experimental groups. The positions of medication were selected on the abdominal skin and on the postauricular skin of all the piglets, and only on the abdominal skin of all the mice. The skins were picked at 2h, 4h, 6h, 12h, 24h, 48h and 72h after the treatments respectively in the groups of piglets, and were excised at 2.25h, 4.5h, 9h, 18h, 36h and 72h after the treatments respectively in the groups of mice. All the collected skins were examined comparatively by light microscopy (LM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: 1. 1. LM results show that the stratum corneum (SC) in the abdominal skins of piglets became looser from 2h to 6h after treatments with lomefloxacin liniment with Azone. These changes were found obviously at 48h. The recovery of the changes was still on at 72h. The SC of mice skin appeared to be the similar changes as piglets, but the viable epidermis of mice skin presented apparent incrassation after treatments with the transdermal liniment of lomefloxacin with Azone at 9h, especially at 36h. The SC of piglet s postauricular skins were looser than that of abdominal skins and the dilated and hemorrhagic vein was found in the dermis of postauricular region in each trail of piglets. 2. The results of SEM indicate that the piglet skin had at least two obvious exfoliations within the medication of 72h.One is between 2-6h after medication, the other is between 24-72h. The SC of mice skin appeared intense desquamation from 2.25h to4.5h.And the orifice of hair follicles did not enlarged obviously in this study. 3. Under TEM, the results reveal that lomefloxacin liniment combined with Azone loosen the outermost SC cell layers, disrupted the keratin pattern, and resulted in swell of basal SC cell layers of piglet and mouse epidermis. Within and between cells of basal SC of piglet epidermis, we found circular or elliptic vacuole and phagosome; many of them were seen at 4h after medication. But in mice, we found circular vesicle with high electron density between cells of basal SC. In addition, we found changes in piglet as follows: the volume of keratohylin in stratum granulosum were increased, especially at 6h and 48h after medication; from 24h to 72h, inflammatory cells were seen in the stratum basale of epidermis; there were many vacuoles with different sizes in the plasma of internal root sheath of hair follicles except 48h group.CONCLUSION: 1. these results of LM and EM suggest that the mechanism of action of Azone as a penetration enhancer are as follows:(l) Azone disrupts the highly ordered lipid structure of SC, and makes the structure of SC loose, which decreases the barrier function of skin for the trandermal absorption of drug. (2) Azone penetrating into the intracellular matrix of SC cells breaks down and fluidizes the filaggrin matrix protein, swells the dermal SC, which could increase the free volume of drug and water content in the SC; (3) Hair follicle is a minor penetration route in the transdermal absorption of lomefloxacin liniment. 2. The change of epidermis caused by Azone is a reversible course. The major time that Azone enhances the absorption of drug is within 6h after medication, the swell and exfoliation of SC in the subsequent time are the result of epidermal Physiological and compensatory hyperplasia. Between 24h and 72h after medication,...