While stability is important, equally important is the ability to release the drug in a controlled fashion at the site of disease. In vitro release assays demonstrated progressive release of drug from the core of the micelle as the pH decreased, which has physiological relevance for delivering drugs to tumors. While passive targeting of nanoparticles within tumor tissue is accomplished by the EPR effect, an Inhibitors,research,lifescience,medical additional layer of targeting is possible by employing active targeting strategies, such as decorating the surface of nanoparticles with targeting ligands [29–33]. It is logical to conclude, however,

that the ability to target a nanoparticle to tumors is dependent on the stability of the nanoparticle in vivo. In pharmacokinetic experiments, superior AUC and Cmax were obtained with several crosslinked micelles, including daunorubicin and BB4007431, compared to their free Inhibitors,research,lifescience,medical drug or uncrosslinked micelle counterparts. These data suggest that higher tumor accumulation, and correspondingly improved antitumor efficacy, would be achieved following

Inhibitors,research,lifescience,medical administration of crosslinked micelle compared to free drug in mouse biodistribution experiments. This would primarily be due to passive targeting by the EPR effect although active targeting has the potential to even further improve delivery of crosslinked micelles. Polymer micelles hold great promise as drug delivery agents. Indeed, many polymer micelles carrying

chemotherapeutic drugs are currently in clinical trials [6, 34]. The utility of a single platform to encapsulate and systemically deliver Inhibitors,research,lifescience,medical hydrophobic cancer drugs allows for faster drug screening and facilitated manufacturing processes. In addition to improving the delivery of Inhibitors,research,lifescience,medical current anticancer drugs, the polymer micelle system presented herein holds promise for the development of potent, but insoluble novel anticancer drugs. It is envisioned that this new technology will ultimately provide superior treatment options for patients with cancer. L-NAME HCl 5. Conclusions A polymer micelle drug delivery system was developed that demonstrated encapsulation and stabilization of a wide variety of hydrophobic anticancer drugs. Drug release from stabilized micelles was determined to be pH dependent in vitro. In vivo pharmacokinetic studies validated increased stability of crosslinked micelles in biological media and demonstrated improved AUC and Cmax compared to uncrosslinked micelles or free drug. These data demonstrate the utility and versatility of a single platform to enable delivery of hydrophobic anticancer drugs to solid tumors.
selleck chemicals llc Bupivacaine is a local anesthetic/analgesic widely used in the perioperative and postsurgical settings.