Gelation of Vesicles and Nanoparticles Using Water-Soluble Hydrophobically Modified Chitosan

Hydrophobically modified chitosan (hmC) is a self-assembling polymer that has attracted recent attention for many applications, including as a hemostatic agent. One limitation with chitosan and its derivatives like hmC is that these polymers are soluble in water only under acidic conditions (because the pKa of chitosan is about 6.5), which could be undesirable for biomedical applications. To circumvent this limitation, we have synthesized a derivative of a C12-tailed hmC that is soluble in water at neutral pH. This water-soluble hmC (ws-hmC) is obtained by grafting O-carboxymethyl groups onto some of the primary hydroxyls on hmC. The solubility of ws-hmC at neutral pH is shown to be the result of a net anionic character for the polymer due to ionization of the carboxymethyl groups (in comparison, hmC is cationic). We also demonstrate that ws-hmC retains the self-assembling properties of hmC. Specifically, ws-hmC is able to induce gelation at neutral pH in dispersions of anionic surfactant vesicles as well as polymethylmethacrylate latex nanoparticles. Gelation is attributed to hydrophobic interactions between the hydrophobes on ws-hmC with vesicle bilayers and nanoparticle surfaces. In each case, gelation can be reversed by the addition of α-cyclodextrin, a supramolecule with a hydrophobic cavity that sequesters the hydrophobes on the polymer

Sprayable Foams Based on an Amphiphilic Biopolymer for Control of Hemorrhage Without Compression

Hemorrhage (severe blood loss) from traumatic injury is a leading cause of death for soldiers in combat and for young civilians. In some cases, hemorrhage can be stopped by applying compression of a tourniquet or bandage at the injury site. However, the majority of hemorrhages that prove fatal are “non-compressible”, such as those due to an internal injury in the truncal region. Currently, there is no effective way to treat such injuries. In this initial study, we demonstrate that a sprayable polymer-based foam can be effective at treating bleeding from soft tissue without the need for compression. When the foam is sprayed into an open cavity created by injury, it expands and forms a self-supporting barrier that counteracts the expulsion of blood from the cavity. The active material in this foam is the amphiphilic biopolymer, hydrophobically modified chitosan (hmC), which physically connects blood cells into clusters via hydrophobic interactions (the hemostatic mechanism of hmC is thus distinct from the natural clotting cascade, and it works even with heparinized or citrated blood). The amphiphilic nature of hmC also allows it to serve as a stabilizer for the bubbles in the foam. We tested the hmC-based hemostatic foam for its ability to arrest bleeding from an injury to the liver in pigs. Hemostasis was achieved within minutes after application of the hmC foams (without the need for external compression). The total blood loss was 90% lower with the hmC foam relative to controls