Phosphonium Polyelectrolyte Complexes for the Encapsulation and Slow Release of Ionic Cargo

Abstract

Polyelectrolyte complexation, the combination of anionically and cationically charged polymers through ionic interactions, can be used to form hydrogel networks. These networks can be used to encapsulate and release cargo, but the release of cargo is typically rapid, occurring over a period of hours to a few days and they often exhibit weak, fluid-like mechanical properties. Here we report the preparation and study of polyelectrolyte complexes (PECs) from sodium hyaluronate (HA) and poly­[tris­(hydroxypropyl)­(4-vinylbenzyl)­phosphonium chloride], poly­[triphenyl­(4-vinylbenzyl)­phosphonium chloride], poly­[tri­(n-butyl)­(4-vinylbenzyl)­phosphonium chloride], or poly­[triethyl­(4-vinylbenzyl)­phosphonium chloride]. The networks were compacted by ultracentrifugation, then their composition, swelling, rheological, and self-healing properties were studied. Their properties depended on the structure of the phosphonium polymer and the salt concentration, but in general, they exhibited predominantly gel-like behavior with relaxation times greater than 40 s and self-healing over 2–18 h. Anionic molecules, including fluorescein, diclofenac, and adenosine-5′-triphosphate, were encapsulated into the PECs with high loading capacities of up to 16 wt %. Fluorescein and diclofenac were slowly released over 60 days, which was attributed to a combination of hydrophobic and ionic interactions with the dense PEC network. The cytotoxicities of the polymers and their corresponding networks with HA to C2C12 mouse myoblast cells was investigated and found to depend on the structure of the polymer and the properties of the network. Overall, this work demonstrates the utility of polyphosphonium-HA networks for the loading and slow release of ionic drugs and that their physical and biological properties can be readily tuned according to the structure of the phosphonium polymer.

Phosphonium versus Ammonium Compact Polyelectrolyte Complex Networks with Alginate—Comparing Their Properties and Cargo Encapsulation

“…13 As reported previously, Et-P, Bu-P, and Hp-P were polymerized to provide M w values of 588 kg/mol for P-Et-P (measured by light scattering), 442 kg/mol for P-Bu-P (D̵ = 2.6, measured by SEC), and 666 kg/mol for P-Hp-P (measured by light scattering). 13 The polymerization of Et-N proceeded with complete conversion (Figure S4). Bu-N was polymerized but required purification by dialysis to remove the residual monomer and afford the pure polymer (Figure S7).…”

“…40,41 Poly[triethyl(4-vinylbenzyl)phosphonium chloride] (P-Et-P), poly[tri(n-butyl)(4-vinylbenzyl)phosphonium chloride] (P-Bu-P), and poly[tris(hydroxypropyl)(4-vinylbenzyl)phosphonium chloride] (P-Hp-P) were also synthesized as previously reported. 13 Triethylamine, tributylamine, 4-vinylbenzyl chloride, fluorescein sodium salt, and D 2 O were purchased from Sigma-Aldrich and used as received. Sodium alginate (Alg), low viscosity, was purchased from Carbosynth (Compton, UK) and used as received.…”

“…Ultraviolet (UV)−visible spectra were obtained on a Tecan Infinite M1000 Pro plate reader using Costar 96-well UV plates (#3635) with UV transparent flat bottoms. The cell toxicity assays were performed as previously reported, 13 and the full procedure is provided in the Supporting Information.…”

“…29 Ionic networks composed of sodium hyaluronate (HA) and four different phosphonium polymers were also explored for drug encapsulation and release. 13 These networks exhibited the ability to self-heal in less than 24 h and were able to retain and release drug molecules over 60 days, making them promising candidates for drug delivery. While ammonium and phosphonium polymers have both been investigated for polyion complex network formation, the properties of analogous ammonium and phosphonium networks have not been directly compared to the best of our knowledge.…”

Weak Polyelectrolytes as Nanoarchitectonic Design Tools for Functional Materials: A Review of Recent Achievements

“…The charges on weak polyelectrolytes are dynamic, causing polymer chains to adopt different equilibrium conformations even with relatively small changes to the surrounding environment [ 174 ] ( Scheme 1 and Scheme 2 ). For instance, phosphonium polymer has been demonstrated to be able to control the physical and biological properties of sodium hyaluronate/phosphonium polyelectrolyte complexes [ 175 ]. The network swelling and therefore drug release rates of these systems can be controlled by varying the concentration of salt in the medium.…”