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

Abstract

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.

Carboxymethyl Chitosan and Its Hydrophobically Modified Derivative as pH-Switchable Emulsifiers

“…In literature, h-CMChi has been employed for reversible gelation of vesicles and nanoparticles. 11 In that study, the reversibility was achieved by the addition of α-cyclodextrin that sequesters the hydrophobic alkyl chains resulting in the degelation.…”

“… 10 These carboxyl and hydrophobic groups containing hydrophobically modified carboxymethyl chitosans (h-CMChi) are amphiphilic and water-soluble. 11 …”

Preparation of Chitosan-Coated Poly(L-Lactic Acid) Fibers for Suture Threads

“…In addition, CS is used prominently as a biomaterial because of its numerous excellent properties, which include biocompatibility, biodegradability, and antibacterial and wound-healing abilities [18][19][20][21]. CS is a cationic polymer bearing amino (-NH 2 ) groups, a consequence of its glucosamine units, and is soluble in acidic aqueous solutions [22]. SA is also a natural biopolymer composed of (1,4) β-D-mannuronate and α-L-guluronate [23].…”

Synthesis of N-alkylated Chitosan and its Aggregation Behavior

“…Among many of its derivatives, hydrophobic modification of CS is a promising one, since they are capable of self-assembling to form micellar nanoparticles with a hydrophobic core in water and therefore it can be used as a hydrophobic drug carrier such as Taxol to improve the stability of drugs and facilitate the delivery and release. [4][5][6] Nowadays, there are many researches based on the hydrophobic alkyl modification of CS biomaterials, which can be synthesized by grafting alkyl onto CS backbone by a reductive method [7][8][9]. However, the effect of alkyl chain length and degree of substitution (DS) on the ability of self-assembling to form micelles is unclear.…”