title: Ionically-crosslinked milk protein nanoparticles as flutamide carriers for effective anticancer activity in prostate cancer-bearing rats.
abstract: In this study, casein (CAS) nanoparticles were used to encapsulate the hydrophobic anticancer drug, flutamide (FLT), aiming at controlling its release, enhancing its anti-tumor activity, and reducing its hepatotoxicity. The nanoparticles were prepared by emulsification of CAS, at pH below its isoelectric point, and stabilized via ionic-crosslinking with sodium tripolyphosphate (TPP). The nanoparticles were spherical and positively charged with a size below 100 nm and exhibited a sustained drug release up to 4 days. After intravenous administration into prostate cancer-bearing rats for 28 days, FLT-loaded CAS nanoparticles showed a higher anti-tumor efficacy as revealed by a significantly higher % reduction in PSA serum level (75%) compared to free FLT (55%). Moreover, the nanoparticles demonstrated a marked reduction in the relative weights of both prostate tumor and seminal vesicle (43% and 32%) compared to free FLT (12% and 18%), respectively. A significantly higher anti-proliferative, anti-angiogenic, and apoptotic effects was demonstrated by the nanoparticles compared to drug solution as evidenced by their ability to decrease the expression of the proliferative marker (Ki-67) and reduce the level of tumor angiogenic markers (VEGF and IGF-1) as well as their ability to activate caspase-3 with subsequent induction of apoptosis in prostate cancer cells. Conclusively, these novel ionically-crosslinked milk protein nanovehicles offer a promising carrier to allow controlled intravenous delivery of hydrophobic anticancer drugs.
authors.affiliation: Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. Electronic address: dr_ahmedelzoghby@yahoo.com.
authors.forename: Ahmed O
authors.initials: AO
authors.lastname: Elzoghby
authors.forename: Noha I
authors.initials: NI
authors.lastname: Saad
authors.forename: Maged W
authors.initials: MW
authors.lastname: Helmy
authors.forename: Wael M
authors.initials: WM
authors.lastname: Samy
authors.forename: Nazik A
authors.initials: NA
authors.lastname: Elgindy
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002364:Caseins / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005485:Flutamide / Q000008:administration & dosage* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D011122:Polyphosphates / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018931:Antineoplastic Agents, Hormonal; D002364:Caseins; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011122:Polyphosphates; D005485:Flutamide; D053148:Caspase 3; C005692:triphosphoric acid
keywords: Casein; In vivo anti-tumor activity; Ionic-crosslinking; Nanoparticles; Prostate cancer; Sustained release