title: Novel ionically crosslinked casein nanoparticles for flutamide delivery: formulation, characterization, and in vivo pharmacokinetics.
abstract: A novel particulate delivery matrix based on ionically crosslinked casein (CAS) nanoparticles was developed for controlled release of the poorly soluble anticancer drug flutamide (FLT). Nanoparticles were fabricated via oil-in-water emulsification then stabilized by ionic crosslinking of the positively charged CAS molecules below their isoelectric point, with the polyanionic crosslinker sodium tripolyphosphate. With the optimal preparation conditions, the drug loading and incorporation efficiency achieved were 8.73% and 64.55%, respectively. The nanoparticles exhibited a spherical shape with a size below 100 nm and a positive zeta potential (+7.54 to +17.3 mV). FLT was molecularly dispersed inside the nanoparticle protein matrix, as revealed by thermal analysis. The biodegradability of CAS nanoparticles in trypsin solution could be easily modulated by varying the sodium tripolyphosphate crosslinking density. A sustained release of FLT from CAS nanoparticles for up to 4 days was observed, depending on the crosslinking density. After intravenous administration of FLT-CAS nanoparticles into rats, CAS nanoparticles exhibited a longer circulation time and a markedly delayed blood clearance of FLT, with the half-life of FLT extended from 0.88 hours to 14.64 hours, compared with drug cosolvent. The results offer a promising method for tailoring biodegradable, drug-loaded CAS nanoparticles as controlled, long-circulating drug delivery systems of hydrophobic anticancer drugs in aqueous vehicles.
authors: Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. dr_ahmedelzoghby@yahoo.com
authors: Ahmed O
authors: AO
authors: Elzoghby
authors: Maged W
authors: MW
authors: Helmy
authors: Wael M
authors: WM
authors: Samy
authors: Nazik A
authors: NA
authors: Elgindy
mesh_terms: D000818:Animals; D002364:Caseins / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D005485:Flutamide / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011122:Polyphosphates; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002364:Caseins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011122:Polyphosphates; D005485:Flutamide; C005692:triphosphoric acid
keywords: biodegradability; casein nanoparticles; controlled release; in vivo pharmacokinetics; ionic crosslinking
references: J Pharm Pharm Sci. 2002 Sep-Dec;5(3):292-8
references: 12553899
references: Biomacromolecules. 2007 Nov;8(11):3345-54
references: 17994786
references: Drug Dev Ind Pharm. 2011 Jul;37(7):754-64
references: 21204753
references: Pharm Dev Technol. 2004 Nov;9(4):369-77
references: 15581073
references: Colloids Surf B Biointerfaces. 2008 Jun 15;64(1):104-10
references: 18294821
references: Pharm Res. 2010 Oct;27(10):2175-86
references: 20703895
references: Contraception. 2000 May;61(5):329-34
references: 10906504
references: Eur J Pharm Biopharm. 2010 Feb;74(2):397-405
references: 19944160
references: Int J Pharm. 2005 May 13;295(1-2):235-45
references: 15848008
references: J Pharm Pharmacol. 1993 Oct;45(10):887-91
references: 7904628
references: J Control Release. 2012 Jul 10;161(1):38-49
references: 22564368
references: Eur J Pharm Biopharm. 2012 Feb;80(2):298-305
references: 22085654
references: Colloids Surf B Biointerfaces. 2010 Jan 1;75(1):1-18
references: 19782542
references: J Colloid Interface Sci. 2007 Dec 15;316(2):405-12
references: 17915243
references: Int J Pharm. 2011 Jun 15;411(1-2):113-20
references: 21457767
references: J Pharm Pharm Sci. 2000 May-Aug;3(2):220-7
references: 10994035
references: J Control Release. 2011 Aug 10;153(3):206-16
references: 21338636
references: Eur J Pharm Sci. 2008 Nov 15;35(4):307-17
references: 18760352
references: Pharm Res. 2013 Feb;30(2):512-22
references: 23135815
references: DICP. 1990 Jun;24(6):616-23
references: 2193461
references: Cancer Treat Rev. 2003 Jun;29(3):171-87
references: 12787712
references: J Control Release. 2012 Jun 10;160(2):164-71
references: 22266050
references: Drug Dev Ind Pharm. 2011 Apr;37(4):446-55
references: 21446829
references: J Young Pharm. 2011 Jan;3(1):4-8
references: 21607048
references: J Control Release. 2012 Jan 30;157(2):168-82
references: 21839127
references: Biopolymers. 2006 Jun 5;82(2):121-33
references: 16453308
references: Colloids Surf B Biointerfaces. 2010 Mar 1;76(1):292-7
references: 20004558