An Experimental Study Of CO₂ Fractional Laser Assisted Topical Drug Delivery

Background:In 2010 ablative fractional laser(AFXL)was introduced as a new drug delivery enhancement technique based on a technique of fractional phototheromolysis.Laser beams create an array of very small thermal injuries in the skin.AFXL systems include the carbon dioxide(CO2,1=10,600 nm)and erbium-doped yttrium aluminium garnet(Er:YAG,1=2,940 nm)lasers.These far-infrared lasers vaporize tissue efficiently,creating an array of very small channels into the skin known as microscopic ablation zones or micro thermal zones(MTZ)The MTZs cross the skin barrier,providing direct access to viable epidermis and dermis until the channels close by local wound repair,without scarring.Ablative fractional laser itself is an evolving treatment modality with numerous clinical applications.Ablative fractional laser-assisted delivery of drugs,fillers,and other substances is rapidly emerging.However assessing the depth and bio distribution of the drug into the dermis without causing adverse effects have rarely been discussed also to evaluate a better formulation for topical application between cream and liquid formulations after fractional carbon dioxide(CO2)laser therapy is yet to be assessed.Hence this clinical study was performed to evaluate the optimal fractional CO2 laser settings required for its depth and bio distribution and to evaluate a better formulations between liquid and cream post laser therapy treatmentMaterial and Methods:Two separate studies were conducted.Firstly for formulation studies 16 foreskin samples were divided into two groups randomly(8 samples each)to compare them between solution formulation with cream formulation and subjected to lOmJ,20%respectively.In laser setting studies,a total of 48 foreskin samples were divided into 6 groups(each group had 8 samples).A pulse energy at 5,10 and 15 mJ and skin coverage at 10%or 20%of fractional CO2 laser were used to illuminate foreskin samples.Post laser therapy all these samples were covered with cream/solution formulations.(including the samples of formulation studies)i.e 64 samples,regardless of different laser settings or formulations were instantly cut into small pieces which were then over laid with plastic film and wrapped in adhesive bandage to shield away from light and to ensure close contact and stored in 5℃ for 20 minutes.After that they were made into frozen sections.The samples were then evaluated by a independent pathologist and standardized pictures taken under the low magnification(4×objective lens)Results:The distribution of cream formulation was extensive and evident all over the epidermis and dermis.The Mean and SEM(Standard error of mean)of the solution formulation was 1.011±0.07153 while it was 1.535±0.2283(p<0.01)of the cream formulation,which statistically suggests that the cream formulation is far more efficacious to the solution formulation.Comparison analysis for both laser depth and cream formulations studies between density of 10%and 20%.it showed no statistically significant differences irrespective of various laser energy used,i.e.5mJ,10mJ,15mJ(p>0.05)and The greater depth of the micro channels did not guarantee greater enhancement of the drug.The microchannels are lined by coagulated cells.The deeper channels produced by higher fluence formed a thicker coagulated lining,which acted as a barrier to drug transport[37]Hence further analysis was performed for cream formulations with 10%density only.Considering that high levels of energy and density causes more pain to the patients and liable to more adverse effects moreover since both 10 and 20%density were also statistically non-significant.In analysis of the laser depth with 10%density showed significant difference between energy of 5mJ and 15mJ(p≤0.01)and similarly between energy of lOmJ and 15mJ(p≤0.01).While there was no difference in the comparison between 5 mJ and 10 mJ(p>0.05).Cream depth Cream depth analysis and its distribution in 10 density with 3 different laser energy(5mJ,15mJ and 20mJ)performed revealed that peak level of significance in cream depth and its distribution was achieved at energy of 15mJ(p≤0.01).However No statistically significant difference was found in neither the energy of 5 mJ and 10 mJ(p>0.05)nor in between the energy of 10 mJ and 15 mJ(p>0.05).Conclusions:According to the study conducted we can assume that cream base formulations was a better medium for transdermal drug delivery post CO2 fractional laser therapy In determining the optimal laser parameter pulse energy of 15mJ and density of 10%would be the ideal laser settings to facilitate the transcutaneous drug delivery to the epidermis and the drug diffusing into the epidermis and dermis with minimal adverse effects.