The physical chitosan hydrogel, obtained by ionic gelation in lactic acid solution, was combined with biocompatible oil-in-water microemulsion with ibuprofen, to prepare composite hydrogels with 0.25–1% of the polymer and 5% of the drug. The electrical conductivity measurement, photon correlation spectroscopy (PCS), and rheological analysis showed that the composite hydrogels comprise oil nanodroplets (16.21–22.56 nm) embedded within pseudoplastic chitosan hydrogel. In vitro ibuprofen release was sustained for 12 h and followed zero-order kinetics. pH values of the composite hydrogels were in the range of 4.80–5.27, thus physiologically acceptable. The formulation containing 0.5% chitosan enabled the maximum drug release rate of 239.25 μgh⁻¹cm⁻² as well as cohesiveness (154.958 ± 0.731 g*s) higher than hardness (13.546 ± 0.065 g) and adhesiveness (−12.042 ± 1.161 g*s), so textural properties were suitable for application along skin surface, without spillage, and for easy removal. This is the first study in which the composite chitosan hydrogels with ibuprofen were formulated by combining the chitosan hydrogel prepared without harmful chemical crosslinkers and low viscosity oil-in-water microemulsion, and the preclinical characterization of their biopharmaceutical aspect and textural characterization, that is of key importance in improving the patient’s compliance, were performed. Graphical Abstract

The formulation of biocompatible drug carriers based on cationic biopolymer chitosan and natural or synthetic polymers represents an important research interest. Therefore, this review aims to perceive their potential in drug delivery. The most investigated chitosan-based polymer blends are polyelectrolyte complexes (PECs) obtained by establishing ionic interactions with biocompatible polyanions as alginates, pectin, xanthan gum, carrageenan, carboxymethylcellulose, and collagen. Depending on the preparation conditions, PECs could be prepared in versatile forms including membranes/films, hydrogel beads, nanoparticles, and microparticles, to achieve controlled (e.g., extended, delayed, colon-specific and pH-dependent) drug delivery. PECs can encapsulate hydrophilic and lipophilic drug substances with different molecular weights. Drug encapsulation allows the preservation of their structure, activity, improvement in absorption efficiency, reduction in adverse effects and long-term stability in vitro and in vivo. The biocompatible structures as non-covalent chitosan-based complexes could be formed also by establishing hydrogen bonds, for example with poly(vinyl alcohol). The swelling of these complexes is not pH-dependent and encapsulated drug substances are often released by already known types of diffusion. Moreover, grafted chitosan derivatives (e.g., carboxymethyl chitosan, trimethyl chitosan, acrylated chitosan) are synthesized to improve water solubility at a wide pH range and enhance the encapsulation capacity of promising PEC-based drug carriers.