title: Food proteins as novel nanosuspension stabilizers for poorly water-soluble drugs.
abstract: Nanonization of the poorly water-soluble drugs is a promising strategy to improve dissolution and oral bioavailability. To stabilize the drug nanosuspensions, stabilizers are usually used; however, the use of common stabilizers is limited by weak stabilization effect and toxicological concerns for long-term treatment. The present work was to investigate the potential of food proteins as novel safe stabilizers for nanosuspensions using indomethacin as a model drug. The nanosuspensions stabilized by food proteins (soybean protein isolate, whey protein isolate and β-lactoglobulin) were prepared by the nanoprecipitation-ultrasonication method. The particle size could be easily reduced to 100-400 nm with bimodal particle-size distribution through monitoring the preparative variables. The exposure of buried hydrophobic moieties due to heat-denaturation and subsequent adsorption onto the surface of drug particles was assumed to contribute to their efficient stabilization effect. In comparison with conventional stabilizers, food proteins are superior in stabilization efficiency. The dissolution was enhanced significantly owing to particle size reduction. The protein-stabilized nanosuspensions could be easily freeze-fried and reconstituted into nanosuspensions, keeping the original mean particle size and particle-size distribution. It is concluded that the three denatured proteins perform as efficient stabilizers for indomethacin nanosuspensions.
authors.affiliation: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education and PLA, Shanghai 201203, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Jianping
authors.initials: J
authors.lastname: Qi
authors.forename: Lingyun
authors.initials: L
authors.lastname: Chen
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D011232:Chemical Precipitation; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry*; D007782:Lactoglobulins / Q000737:chemistry; D008894:Milk Proteins / Q000737:chemistry; D053758:Nanoparticles; D010316:Particle Size; D012995:Solubility; D030262:Soybean Proteins / Q000737:chemistry; D013535:Suspensions; D014465:Ultrasonics; D000067816:Whey Proteins
chemical_list: D005079:Excipients; D007782:Lactoglobulins; D008894:Milk Proteins; D030262:Soybean Proteins; D013535:Suspensions; D000067816:Whey Proteins; D007213:Indomethacin