Preparation And Primary Clinical Application Of Stearic Acid Solid Lipid Nanoparticles Containing Podophyllotoxin

Solid lipid nanoparticles (SLN) are nanoparticles generally made from solid lipids by high pressure homogenization. Combining advantages of the traditional systems but avoiding some of their major disadvantages, SLN represent an alternative carrier system to traditional colloidal carriers, such as emulsions, liposomes and polymeric nanoparticles.Early work on Solid lipid nanoparticles dispersions mainly focused on the parentearl route of drug administration, sustained release and drug targeting were the primary objectives. Only recently have the peroral or dermal use been evaluated. Drugs encapsulated into SLN showed a reduced peak plasma concentration and prolonged therapeutic drug level following oral administration. More-over, their bioavailability appeared more reproducible as compared to a commercial formulation.Because SLN are based on non irritative and non toxic lipids they seem to be well suited for use on damaged or inflamed skin. Sustained drug release properties can also be useful for dermal formulations. For example, for topical antibiotics it is desirable to maintain high drug concentrations over a prolonged time on the skin surface and within the skin tissue. Moreover, irritant drugs like benzoyl peroxide or tretinoin turned out to less irritating if applied in a controlled release device. This also reduces systemic uptake of the active agent. With respect to their use as carriers for drugs and cosmetics, further favorable properties of SLN include an occlusion effect due to film formation on the skin surface which reduces transepidermal water loss. Occlusion also favours drug penetration into the skin. The high specific surface area of nanometer sized SLN facilitates contact of encapsulated drugswith the stratum corneum.The anti-recurrence therapy of condyloma acuminatum is a very difficult task. LPI (Latent papillomavirus infection) is believed as one of the major factors of high recurrence. Controlled-sustained release system and targeting treatment can increase drug effectiveness and reduce adverse effect of drugs, if used in podophyllotoxin which is recommended by WHO to cure condyloma acuminatum, will ameliorate the drug's pharmacokinetic aspects and pharmacodynamic aspects. It may be a new method to suppress the latent infection of HPV or to prevent recurrence of CA and HPV related tumor. We are to make primary research to study podophyllotoxin SLN's preparation, property and topical application effect in Clinic. Methods:1. To prepare stearic acid solid lipid nanoparticles containing podophyllotoxin with the method of modified microemulsion technique, its morphology was examined by transmission electron microscope, the HPLC method for determination of podophyllotoxin in nanoparticles.2. We chose carbomer 940 as a base in the gel, Freeze-drying and mixing method were used to prepare PDT-SLN gel .The quality control standard was established in respect to the property, PH value, hygienic index, et al.3. In a randomized, double-blind study two kinds of drugs, podophyllotoxin SLN gel and ordinary preparation of podophyllotoxin gel was applied with volunteer patients. The therapeutic effect, anti-recurrence effect and adverse effect was discussed.Results:1. The mean diameter of podophyllotoxin SLN is (56.5 +25.8) nm, mean entrapment efficiency is 85.6% and the dispersions are stable.2. The prepared gel exhibited a fine consistency and transparency. PH of the preparation was 7.2, the examination of microbial limitation accorded with standard .in addition, the gel was stable and no change occurred after stability test.3. Wart clearance rate (the first course) applied with PDT-SLN gel to condyloma acuminatum was 97.1%, close to that of the ordinary preparation, 90.6%. However its recurrence and adverse effect rate is lower.Conclusion:1. Podophyllotoxin SLN has high entrapment efficiency, an even distribution in size and a satisfactory stability, indicating that it might be a hopeful skin topical preparation in...