Primary Experimental Research Of Targeting Distribution In Normal Skin After Liposome Podophyllotoxin Topical Application In The Rat

The incidence rates of condyloma accuminatum(CA) is increasing annually. It is the second of sexually transmitted diseases (STDs) in our country now. There are no effective anti-virus therapeutic methods so far;and parts of CA can transform into squamous cell carcinoma or cervix cancer. The infection of HPV is discovered in 90% of carcinoma or anaplasia of cervix. Therefore,the CA has become the serious problem of threatening healthy of people. Many methods can treat warts and it is very easy to remove the obvious warts,however,any method has high recurrence rate. In addition,the latent infection of HPV that is main reason of recurrence has not effective method to diagnose clinically now. Therefore,the incidence,dissemination and spread of CA are difficult to prevent and control. It can hardly be avoided of recur in situation or in other places after therapy. Therefore,some progresses have to be made to treat the latent part. The study of targeting-drug vehicles is the important theory and applied worth at present. As drug-delivery vehicles liposome is one of hot spots .Use of specific liposome encapsulated podophyllotoxin can accumulate and slowly release in epidermis cells infected of HPV,will improve ameliorate the drug's pharmacokinetic aspects and pharmacodynamic aspects. It may be a new method to suppress the latent infection of HPV or prevent recurrence of CA and related tumor. We are to make primary research to study distribution,regular pattern of liposome podophyllotoxin in skin. The purpose of this study:1. To study distribution regular pattern of liposome podophyllotoxin in animal skin2. Investigate the change of serum concentrations of podophyllotoxin after topical applying liposome-podophyllotoxin suspension on rat skin.3. To evaluate the effect to hepatic and renal functions after liposome-podophyllotoxin topical application.Materials and methods:1. Liposome-podophyllotoxin was made ideal formulations according to early study methods,and control group was taken with podophyllotoxin alcohol solution. Two drugs were applied on rat skin under the principle of random and comparison. After a regulated time the skin was samples were taken and made into optical sections. Confocal laser scanning microscopy was used to detect the fluorescence,comparing their different and distribution regular pattern in skin.2. Two kind of drugs,Liposome-podophyllotoxin and podophyllotoxin alcohol solution,were applied on rat skin under the principle of random and comparison. The serum concentration of podophyllotoxin was detected by spectrofluorometry. The results were discussed.3. Liposome-podophyllotoxin was made ideal formulations according to early study methods,and control group was taken with podophyllotoxin alcohol solution. Two drugs were applied on rat skin under the principle of random and comparison. The drugs were applied on the rats skin twice a day for three days. To detect hepatic and renal functions after four days.Results:1. Confocal laser scanning microscopy shows that the AUC of fluorescent in epidermal and dermal test group is 1.5~2.3-fold higher than that of control. Unit area fluorescent amount of epidermal and dermal was highest after 2h in control group(l 585.527 u m2 and 2005.66 7u m2),and quick reduced after 4h;But unit area fluorescent amount of epidermal and dermal was rather low before 4h in observing group,and gradually increased after 6h,and was highest after 12h (750.287 u m2 and 1073.087 um2) .2. The AUC of podophyllotoxin control group is 2.3-fold higher than that of the test. After 8h topical application,the serum concentration of podophyllotoxin was the highest in test group,while it reached in 2h as far as control group was concerned. The highest serum concentrations of podophyllotoxin in test group were significantly lower than those in control group (P<0.001).3. There were no differences between test group and control group andspace group in hepatic and renal functions (P>0.05) Conclusion:1. Podophyllotoxin of lipos...