Sprague-Dawley rats were given a single intravenous administration of crosslinked daunorubicin

micelle, uncrosslinked daunorubicin micelle, or free daunorubicin at a 10mg/kg dose. Plasma … Figure 6 Pharmacokinetics of crosslinked BB4007431 micelles in rats. Sprague-Dawley rats were given a single intravenous administration of crosslinked BB4007431 micelle, or free BB4007431 at a 25mg/kg dose. Plasma was analyzed for BB4007431 concentration … 4. Discussion Improving stability of therapeutic molecules is a well-established aim in the field Inhibitors,research,lifescience,medical of drug delivery. An ideal drug-loaded nanoparticle would be stable to dilution in biological media, possess stealth-like properties to avoid uptake by the RES, and release the drug only in the area of diseased tissue. The data presented in this paper describe a versatile polymer micelle drug delivery system that has been engineered to efficiently Inhibitors,research,lifescience,medical encapsulate a wide variety of hydrophobic drugs. In addition, the stabilization technology

built-in to the micelle is dependent on pH, such that the micelle is stable at physiological pH, and unstable at low pH, thus providing a mechanism to release the drug in the tumor microenvironment or in endosomes, which are both slightly acidic environments. A vast number of drugs exist today that possess potent Inhibitors,research,lifescience,medical anticancer activity; however, many of them are unable to be utilized in the clinic due to their inability to be dissolved in aqueous solutions [27]. Some hydrophobic drugs can be solubilized with excipients; however, such vehicles have been shown to cause toxicity to the patient [28]. Inhibitors,research,lifescience,medical The core block of the triblock copolymer (poly(D-leucine-co-tyrosine)) was rationally designed and chosen to encapsulate

hydrophobic molecules. A key factor leading to the versatility arises from the use of both D and L stereoisomers of amino acids in the core block, which disrupts the secondary structure of the polypeptide. Replacing the rod-like helical nature of the polypeptide Inhibitors,research,lifescience,medical with the flexibility of a random coil allows for significant increases in drug loading efficiency. The ability of drugs to be encapsulated within the triblock copolymer was the related to its LogP value, such that only hydrophobic drugs could be encapsulated. This result is logical as hydrophilic molecules would prefer to associate with the hydrophilic part of the polymer versus the hydrophobic core, leading to inefficient drug encapsulation. Crosslinking was performed using metal acetate chemistry, specifically, iron (II) chloride. The crosslinking dialysis assay determined that 40–90% of the drug remained in the crosslinked micelle after six hours. Typically, 10% of the drug or less was VE-821 mw retained in uncrosslinked micelles examined using the same crosslinking dialysis assay. Although there was a correlation between LogP and encapsulation ability, there was no clear correlation between LogP and the crosslinking retention or the particle size.