Micellar Delivery of Flutamide Via Milk Protein Nanovehicles Enhances its Anti-Tumor Efficacy in Androgen-Dependent Prostate Cancer Rat Model

• Published in: Pharmaceutical research Vol. 30; no. 10; pp. 2654 - 2663
• Main Authors: Elzoghby, Ahmed O., Helmy, Maged W., Samy, Wael M., Elgindy, Nazik A.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.10.2013; Springer; Springer Nature B.V
• Subjects: Androgens - metabolism; Animals; Antineoplastic agents; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - therapeutic use; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cancer therapies; Caseins - chemistry; Delayed-Action Preparations; Drug Carriers - chemistry; Drug Compounding; Drug delivery systems; Flutamide - administration & dosage; Flutamide - therapeutic use; General aspects; Gynecology. Andrology. Obstetrics; Male; Male genital diseases; Medical Law; Medical sciences; Micelles; Nanoparticles; Nanoparticles - chemistry; Nephrology. Urinary tract diseases; Particle Size; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Proteins; Rats; Rats, Sprague-Dawley; Research Paper; Solubility; Surface Properties; Toxicity; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; casein micelles; prostate cancer; hydrophobic anti-cancer drugs; hepatotoxicity; anti-tumor efficacy; spray-drying; Antineoplastic agent; Prostate disease; Rat; Toxicity; Liver; Micelle; Antihormone; Casein; Efficiency; Non steroid compound; Male genital diseases; Hormonodependence; Urinary system disease; Androgen; Rodentia; Spray drying; Antiandrogen; Malignant tumor; Vertebrata; Mammalia; Flutamide; Treatment; Animal; Animal protein; Prostate cancer; Cancer
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-013-1091-7

ABSTRACT Purpose This article describes the preparation, physicochemical characterization and in vivo assessment of parenteral colloidal formulation of flutamide (FLT) based on biocompatible casein (CAS) self-assembled micelles in order to control drug release, enhance its antitumor efficacy and reduce its hepatotoxicity. Methods Spray-drying technique was successfully utilized to obtain solidified redispersible drug-loaded micelles. Results Spherical core-shell micelles were obtained with a particle size below 100 nm and a negative zeta potential above −30 mV exhibiting a sustained drug release up to 5 days. After intravenous administration into prostate cancer bearing rats for 28 days, FLT-loaded CAS micelles showed a higher antitumor efficacy as revealed by significantly higher reduction in PSA serum level (65.95%) compared to free FLT (55.43%). Moreover, micellar FLT demonstrated a marked decrease in relative weights of both prostate tumor and seminal vesicle (34.62 and 24.59%) compared to free FLT (11.86 and 17.74%), respectively. These antitumor responses were associated with notable reduction of cell proliferation, intratumoral angiogenesis and marked increase of tumor apoptosis. A significantly lower risk of hepatotoxicity was observed by micellar FLT as evidenced by lower alanine aminotransferase (ALT) serum level compared to free FLT. Conclusions Overall this approach suggested that CAS micelles might be an ideal candidate for intravenous delivery of hydrophobic anticancer drugs.