Formulation and evaluation of colloidal nanocarriers for the management of skin cancer / Hemat Hassan Attia Rashed, Pharmacist at Dar El Salam Cancer Hospital; supervised by Prof. Dr. Dalia Samuel Shaker, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Prof. Dr. Aliaa Nabil ElMeshad, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Dr. Maha Osama Abd El-Aziz, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Future University.

supervised by Prof. Dr. Dalia Samuel Shaker, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Prof. Dr. Aliaa Nabil ElMeshad, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Dr. Maha Osama Abd El-Aziz, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Future University.

Thesis (M.Sc.)-Future University in Egypt, Faculty of Pharmacy, Department of Pharmaceutics and Pharmaceutical Technology, 2024.

Includes bibliographical references.

Skin cancer represents the most widely recognized type of cancer among all the recorded malignancies. Seeking for an alternative therapies using safe noninvasive drug, such as proniosomal gels containing carvedilol (CAR) is desirable in order to overcome the drawbacks that might exist upon using conventional skin cancer treatment options. However, its application in topical formulations has been problematic owing to its chemical instability and low bioavailability that result in inefficient delivery.
Therefore, in the present study, proniosomal gels containing carvedilol (CAR) were formulated, using various non-ionic surfactants (NISs) in combination with cholesterol for topical administration that can offer a good solution for the numerous CAR problems associated with the use of free CAR. Moreover, the topical administration would ensure drug targeting to skin tumors which can further enhance its chemotherapeutic potential in the treatment of skin cancer. The prepared proniosomal gel formulae were examined for the colloidal properties. A preliminary study (chapter I) was carried out in for the optimization of the colloidal properties of the prepared vesicles (namely particle size, polydispersity index and zeta potential) through preparing empty vesicles. Further optimization trials were performed on CAR-loaded vesicular systems through changing the loading amount of drug in vesicular carriers in order to achieve high drug loading with good colloidal properties. Vesicle size, size distribution (PDI), zeta potential (Z.pot) and entrapment efficiency (%EE) was carried out on the optimized formulae after increasing loading dose. In chapter II of the study ex-vivo skin permeability, deposition investigation, visualization using TEM, and stability study was conducted on the two selected formulae F3.3 (12mg) and F5.5 (20). As control the CAR dispersion containing equivalent amounts of the drug to their corresponding formulae were used.
In-vitro cytotoxicity study using Human Melanoma cell line (A375) and in-vitro free radical scavenging activity using DPPH were performed in chapter III using the two selected formulae F3.3 (12mg) and F5.5 (20). Blank formulae for vesicular carrier (formulae without loading the drug) were used with the CAR dispersion containing equivalent amounts of the drug to their corresponding as control.
All proniosomal formulae prepared using cholesterol and different NIS types were in the nano-size range. Adequate size distribution results were obtained where vesicles exhibiting particle size (242-712) showed PDI with average ≤ 0.5 reflecting mono-disperse dispersion and acceptable zeta potential values that were sufficiently high to provide adequate repulsion between the vesicles and encounter electrostatic stabilization.
CAR was efficiently entrapped in all prepared proniosomal gels (Up to 96%) %EE marked increase upon increasing the CAR loading dose in all the prepared vesicles along with accompanying increase in particle size. Direct correlation was observed between the particles size and %EE of the prepared vesicles.
Formulae F3.3 (12 mg) and F5.5 (20 mg) were selected as the optimal formulae for further investigations, since they exhibited the highest %EE values (≈95.5%) with acceptable particle size (≈420 nm) and uniform size distribution (PDI < 0.5) to fulfill the goal of our study; retaining the maximum drug amounts in different skin layers with minimal permeation in a trial to target the drug to the skin.
Results revealed that the prepared vesicles had a relatively high CAR entrapment efficiency and were in the nano-size range. Ex-vivo skin permeability and deposition results demonstrated the superiority of CAR proniosomal gel over free drug dispersions. The optimized CAR-loaded proniosomal gel showed a prominent cytotoxic activity on human melanoma cell line (A375), which was further confirmed by the results of DPPH free radical scavenging activity. Findings of this study suggest that the proniosomal gel F5.5 (20 mg) comprised of Span 40, Tween 80 and cholesterol in a 3:6:1 ratio and loaded with 20 mg CAR displayed enhanced skin deposition, potent antioxidant properties and significant cytotoxic activity, suggesting it to be a propitious and effective topical delivery system for treating melanoma.
Therefore, the encapsulation of CAR in proniosomal gel containing vesicles succeeded in offering an effective delivery system targeting skin cancer, in an attempt to widen the scope of CAR dermal delivery by rapidly crossing the stratum corneum and releasing the encapsulated drug at deeper skin layers. In addition, the optimized CAR-loaded vesicular system protected the encapsulated drug against degradation, improving the antioxidant capacity and anticancer efficacy of CAR.

Text in English, abstracts in English and Arabic.