Author: Mahmoud, Mona Ahmed./ Title: Preparation of Nano Dosage Forms for Novel Anticancer Agents and Pharmacokinetic Evaluation Using Radio-Labeling Technique /

الموضوع

The goal of the current thesis was to formulate niosomes of acemetacin (ACM) and mefenamic acid (MEF) and developed them to improve their tumor targeting in addition to radio-kinetic evaluation performed using 131I. Niosomes were prepared by ether injection method and characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%) and in vitro drug release. Factors affecting radiolabeling with 131I were studied and optimized. Radio-kinetic evaluation was done for 131I-ACM optimum niosomal and 131I-MEF optimum niosomal formula by intravenous (I.V) administration to solid tumor bearing mice and compared to I.V 131I-ACM solution and I.V 131I-MEF solution as a control, respectively. The average droplet size, zeta potential and in vitro release after 24 h for the optimum ACM niosomal formula were 315.23 ± 5.37 nm, − 9.16 ± 2.91 and 76 %, respectively. The greatest labeling yield of 131I-ACM was 93.1 ± 1.1%. Radio-kinetic evaluation showed a maximum tumor uptake of 5.431 %ID/g for 131I-ACM niosomal formula and 2.601 %ID/g for 131I-ACM solution at 60 min post I.V. injection. While the average PS and ZP values for the optimum MEF niosomal formulation were 247.23 ± 2.32 nm and – 28.3 ± 1.21, respectively. In vitro release study of the optimum formula showed appropriate cumulative drug release of (77.73 %) after 24 hr. The highest labeling yield of 131I-MEF was 98.7  0.8%. The biodistribution study revealed that the highest tumor uptake of 131I-MEF niosomal formula and 131I-MEF solution at 60 min after I.V. injection were 2.73 and 1.94 % ID/g, respectively. As a conclusion, ACM-loaded niosomes and MEF-loaded niosomes are excellent substitutes in cancer treatment due to enhanced tumor uptake of 131I-ACM and 131IMEF by passive targ