5339
Mona Mohammad Abd Elmageed Agwa
Application Of Protein Nanocarriers For Tumor- Targeted Delivery Of Anticancer Drugs
Nanocarriers, Tumor, Anticancer, lung cancer
Several studies revealed the beneficial effect of co-administration of the natural pigment Prodigiosin with cytotoxic chemotherapeutic drugs owing to its down regulation for survivin a member of the inhibitor of apoptosis (IAP) family. This is in turn sensitizing the cancer cell to the effect of cytotoxic chemotherapeutic drugs and synergistically enhanced its death. The purpose of this study was to isolate β- casein (β-CAS) from bovin skimmed milk and Prodigiosin from Serratia marcescens to fabricate a novel natural protein nanocarrier for tumor-targeted co-delivery of Etoposide (ETP) and Prodigiosin (PRO) in lung cancer therapy via inhalation route which is the favoured route of administration of drugs over parenteral and oral routes. Also coating of β-CAS by either Lactoferrin (LF) or chitosan (CS) was achieved via electrostatic interaction for preparation of dual drug loaded β-CAS nanocarrier.The optimal nanoformulations that showed high (% EE) of both drugs, sustained drug release and suitable nanometer size range were then subjected to spray drying using suitable excibient (mannitol or hydroxy propylated beta cyclo dextrin) and Leucin as dispersibility enhancer. A total of nine spray-dried powders with different ratio of carriers were prepared and characterized aiming to develop a powder formulation with the highest emitted dose and fine particle fraction. Complete physicochemical characterization of the SD powders was performed including particle size measurements, X-ray diffraction, IR, SEM, flow properties and DSC. Reconstituted SD powders were characterized in terms of particle size, zeta potential and size distribution. Aerosol performances of spray-dried powders were evaluated using the twin stage glass impinger and the Aerolizer® as the inhaler to determine the aerodynamic performance and fine-particle fraction that is theoretically able to reach the lung. All the formulations when developed as dry powder inhalers showed significant in vitro lung deposition pattern in cascade impactor with a respirable faction in the range of 63.048-38.93%. Further, in-vitro cellular uptake and cell cytotoxicity of the prepared optimized SD-powders that showed higher deep lung deposition were evaluated using the MTT assayon human adenocarcinomic alveolar basal epithelial cells (A549 cells). The MTT cytotoxicity assay of the selected optimized spray dried formulae demonstrated a good safety profile and reduction in cytotoxicity combared to the free drugs. The study opens up a new strategy to treat lung cancer especially in cases of drugresistance. Moreover direct delivery to lung may provide an important role in complete remission of the disease due to target specificity.
2017
Ph.d
Alexandria
Institute of post graduate childhood studies