Beta-casein nanovehicles for oral delivery of chemotherapeutic drugs.
Bovine beta-casein (beta-CN) is an abundant milk protein that is highly amphiphilic and self-assembles into stable micellar structures in aqueous solutions. Here we introduce a drug-delivery system comprising a model hydrophobic anticancer drug, mitoxantrone (MX), entrapped within beta-CN-based nanoparticles. This novel drug-delivery system allows hydrophobic drugs to be thermodynamically stable in aqueous solutions for oral-delivery applications aimed at treatment of various disorders. The gastric digestibility of beta-CN suggests possible targeting to stomach tumors. Dimethyl sulfoxide (DMSO)-dissolved MX was entrapped in beta-CN nanoparticles by stirring this solution into phosphate-buffered beta-CN solution. High-affinity MX-beta-CN association was found (K(a) = [2.15 +/- 0.30] x 10(6) M(-1)). The optimal nanovehicle formation conditions were 1 mg/mL beta-CN, <or=6% (vol/vol) DMSO in phosphate-buffer solution, 10 mM MX in DMSO, and a MX:beta-CN molar-ratio of approximately 4:1. Under these conditions, particles of 100 to 300-nm diameter were formed. beta-CN nanoparticles may serve as effective oral-delivery nanovehicles for solubilization and stabilization of hydrophobic drugs.


BACKGROUND
Bovine beta-casein (beta-CN) is an abundant milk-protein that is highly amphiphilic and self-assembles into stable micellar-structures in aqueous solutions. beta-CN nanoparticles may serve as effective oral-delivery nanovehicles for solubilization and stabilization of hydrophobic drugs, as demonstrated in this study utilizing methotrexate.
Shapira
Alina
A
Russell Berrie Nanotechnology Institute, Technion, Israel Institute of Technology, Haifa, Israel.
Assaraf
Yehuda G
YG
Livney
Yoav D
YD
D000284:Administration, Oral; D000818:Animals; D002364:Caseins / Q000378:metabolism*; D002417:Cattle; D004337:Drug Carriers / Q000737:chemistry*; D005453:Fluorescence; D008823:Micelles; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000494:pharmacology*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013696:Temperature; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism
D002364:Caseins; D004337:Drug Carriers; D008823:Micelles; D014364:Tryptophan; D008942:Mitoxantrone