Polyquaternium-4

Rodrı́guez, R., Alvarez-Lorenzo, C., & Concheiro, A. (2003). Journal of Controlled Release, 86(2-3), 253-265.

Polyquaternium-4 (PQ-4), a cationic hydroxyethylcellulose with a relatively high content of hydroxyethyl substituents and lower intrinsic viscosity, has been demonstrated as an efficient precursor for the preparation of chemically cross-linked cellulose hydrogels. In a representative study, PQ-4 was cross-linked with ethylene glycol diglycidyl ether (EGDE) under alkaline conditions to form three-dimensional, water-swellable polymer networks suitable for controlled drug delivery applications.

Rheometric time-sweep experiments revealed that effective cross-linking of PQ-4 requires a minimum NaOH concentration of 0.05 M and temperatures above 30 °C, confirming the base-catalyzed activation of EGDE. The evolution of elastic (G′) and viscous (G″) moduli followed first-order kinetics, with G′ increasing more rapidly than G″, indicating progressive network formation. Compared to polyquaternium-10, PQ-4 exhibited a higher cross-linking rate, attributed to its lower initial viscosity and greater accessibility of reactive hydroxyl groups. Apparent activation energies derived from gel times ranged from 70 to 90 kJ mol⁻¹.

Under optimized conditions (0.10 M NaOH, 60 °C), PQ-4 hydrogels were transparent, mechanically stable, and superabsorbent, without evidence of polymer depolymerization. The resulting hydrogels showed significant loading capacity for diclofenac sodium through combined ionic and hydrophobic interactions. Drug release was strongly pH-dependent: retention under acidic conditions and sustained release at pH 8 for over 4 h.

These findings highlight polyquaternium-4 as a versatile cationic cellulose derivative for fabricating pH-responsive hydrogels with potential in site-specific drug delivery systems.

Rodrıguez, R., C. Alvarez-Lorenzo, and A. Concheiro. European journal of pharmaceutics and biopharmaceutics 56.1 (2003): 133-142.

Polyquaternium-4 (PQ-4), a cationic hydroxyethylcellulose widely used in cosmetics and topical drug delivery systems, has been extensively investigated as a model polymer for understanding surfactant–polymer interactions and their impact on hydrogel behavior. In a representative study, the interaction between PQ-4 and sodium dodecyl sulfate (SDS) was systematically analyzed in both aqueous dispersions and chemically cross-linked hydrogels.

Multitechnique characterization—including surface tension, fluorescence spectroscopy, microcalorimetry, viscosity, and oscillatory rheometry—demonstrated that SDS binds strongly to PQ-4 through a combination of electrostatic attraction between ammonium and sulfate groups and hydrophobic interactions. The critical aggregation concentration (cac) was identified at 0.05% SDS, corresponding to an ammonium/sulfate ratio of 2.61, significantly lower than values reported for non-ionic cellulose ethers. This highlights the dominant role of ionic interactions in PQ-4/SDS affinity. The binding process was strongly exothermic and insensitive to physiological salt concentrations, indicating robust interaction behavior.

Rheological analysis revealed a dramatic increase in both elastic (G′) and viscous (G″) moduli—up to four orders of magnitude—near charge neutralization, where a stable three-dimensional network was formed without precipitation. In contrast to polyquaternium-10, PQ-4 dispersions and hydrogels remained structurally coherent due to the presence of free hydrophilic hydroxyethyl groups that prevent aggregate collapse.

Surfactant-induced shrinking experiments further showed that PQ-4 hydrogels undergo only moderate volume reduction at neutralization, confirming superior structural stability. These findings establish polyquaternium-4 as an excellent platform for designing surfactant-responsive hydrogels and for predicting dispersion behavior in pharmaceutical and cosmetic formulations.