الفهرس 
General IntroductionOnly 14 pages are availabe for public view
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Abstract
Psoriasis is one of the majorly encountered skin diseases accompanied by several severe effects such as the formation of scales called psoriatic plaques with severe inflammatory episodes, and extensive dryness of skin surface causing insurmountable problems for the patient. Also, psoriasis is one of chronic diseases requiring long periods of treatment resulting to the emergence of many side effects favoring topical drug treatment. It was found that the skin of psoriatic patients are severely depleted from ceramide which is a type of skin lipids (sphingolipids), that reduces the rate of skin cell death leading to rapid growth of these cells and the appearance of specific plaques of the disease and many studies have suggested that ceramide can be used in treating many skin diseases suffering from rapid cells multiplication including psoriasis
Tazarotene is the third generation of retinoid family medically recommended for use in topical treatment for many skin diseases including psoriasis
Nowadays, to improve the effect of medicine used topically, attempts are made to develop novel local delivery systems like vesicular systems which have proven their ability to achieve better drug penetration and optimum deposition at the required site of action, leading to enhanced therapeutic effectiveness.
Therefore, the aim of this work was to develop new tazarotene vesicular systems containing ceramide for optimum therapeutic effect.
Accordingly, the work was divided into two chapters as follows:
Chapter I: Preparation and characterization of different tazarotene vesicles.
Chapter II: Clinical Study on selected ceramide containing vesicles on psoriatic Patients.
Chapter I: Preparation and characterization of different tazarotene vesicles
This chapter was concerned with the preparation of tazarotene containing cerosomes, and ceramide free tazarotene vesicles using the thin film hydration method. Two types of surfactants were used in the vesicular formulations; Tween 80 and SDC with different amounts of ceramide. After preliminary studies, cerosomes were prepared according to factorially design experiment to assess the effect of different variables and their amounts on the EE%, viscosity, and in vitro release of the vesicles. The vesicles were further characterized by TEM, DSC, and ex-vivo skin deposition studies on different formulae, followed by stability study on selected formulae for clinical study. Results of this chapter revealed that:
1. Ceramide alone was incapable of forming vesicular structures without surfactant addition.
2. Tazarotene EE% increased with increasing ceramide content.
3. The addition of ethanol decreased the drug EE%.
4. The highest EE% values were obtained when using the highest ceramide: surfactant ratio (9:1) in absence of alcohol when using SDC as surfactant , and the lowest EE% was obtained obvious with the lowest ceramide: surfactant ratio (1:1) in presence of alcohol and using Tween as surfactant.
5. The edge activator was the key factor influencing the vesicular viscosity.
6. Regardless the type of used surfactant, decreasing ceramide: surfactant ratio increased the vesicular viscosity, with higher increase of Tween containing formulations than their counterparts containing SDC.
7. Ethanol addition led to significant increase in viscosity compared to other formulae prepared without ethanol addition.
8. The highest viscosity was obtained when using the lowest ceramide: surfactant ratio (1:1) in presence of Tween and in presence of ethanol, while the lowest viscosity was obtained when using the highest ceramide: SDC ratio (9:1) in absence of ethanol.
9. The in vitro release study over 24 hours showed the extremely low release of tazarotene.
To determine the effect of ceramide addition on vesicular properties, ceramide free vesicles were prepared showing the following results:
1. Phosphatidylcholine as a sole lipidic member was capable of forming stable vesicular systems.
2. SDC containing vesicles showed higher EE% than corresponding ones containing Tween.
3. Ethanol decreased the drug’s EE%.
4. Formulae containing Tween 80 as surfactant showed higher viscosity than their SDC containing analogues.
5. All ceramide free vesicles showed relatively low in-vitro release over 24 hours except F16 and 17 containing Tween 80 as surfactant.
6. Addition of ethanol decreased the vesicular particle size.
7. The type of surfactant didn’t affect the vesicular particle size.
8. Ethanol containing formulae showed lower negative charge on the vesicles than their corresponding ethanol free ones.
9. SDC containing vesicles showed higher negative charge values than Tween containing formulae.
10. TEM examination showed the liposomes, transfersomes, and ethosomes as well identified spherical vesicles, with thinner wall for ethosomal ones.
11. Cerosomal vesicles showed unique tubular forms which appeared as intertwined filaments owing to ceramide presence.
12. DSC of tazarotene showed an endothermic peak at 124.6˚C, while the DSC of ceramide showed no thermal events, with disappearance of tazarotene peak in the formulae indicating complete drug solubilization in the phospholipid bilayer.
13. Ex-vivo study for selected cerosomal formulae showed high drug deposition after 24, 48, and 72 hours, while the ex-vivo study for the ceramide free vesicles was almost similar to the marketed product and lower than cerosomal ones.
14. Chosen formulae showed remarkable stability in EE% over one year storage at refrigeration temperature.
Chapter II: Clinical Study of selected ceramide containing vesicles on psoriatic Patients
In this chapter, we evaluate the clinical efficacy of the chosen formulae in psoriasis treatment. Twenty patients were selected for this study, and results of formulae (1 and 6) were compared with marketed product. Patients were divided into two groups one receiving formula 1 (group A) and the other formula 6 (group B) with control Acnitaz® gel product. Study was performed by applying different drug preparations on the same patient to ensure comparable responses. The severity of psoriasis was evaluated using PASI score and statistically compared before and after treatment. By analyzing the results of this chapter it was revealed that:
1. Formula 1 led to approximately 65% reduction in the mean PASI score after 8 weeks of treatment.
2. Formula 6 and Acnitaz® gel, both led to approximately 30% reduction in the mean PASI score after 8 weeks of treatment.
3. Formula 1 containing ethanol and higher amount of ceramide was more efficacious than formula 6.
4. Prepared formulae were characterized by lacking of patients complaints concerning skin sensitization or burning sensation upon application, unlike what is known and observed with marketed product Acnitaz® reflecting the successful tazarotene encapsulation, and confirms that the prepared formulae were characterized by minimizing drug side effects.
Findings of this thesis suggest that cerosomes, as novel vesicular delivery were successful for loading tazarotene and achieving a better therapeutic outcome in psoriatic patients compared to the marketed product.