Evaluation of Physically and/or Chemically Modified Chitosan Hydrogels for Proficient Release of Insoluble Nystatin in Simulated Fluids

Abstract

To avoid fungal spreading in the bloodstream and internal organs, many research efforts concentrate on finding appropriate candidiasis treatment from the initial stage. This paper proposes chitosan-based physically or chemically cross-linked hydrogels aimed to provide sustained release of micronized nystatin (NYSm) antifungal drug, known for its large activity spectrum. Nystatin was demonstrated itself to provide hydrodynamic/mechanic stability to the chitosan hydrogel through hydrophobic interactions and H-bonds. For chemical cross-linking of the succinylated chitosan, a non-toxic diepoxy-functionalized siloxane compound was used. The chemical structure and composition of the hydrogels, also their morphology, were evidenced by infrared spectroscopy (FTIR), by energy dispersive X-ray (EDX) analysis and by scanning electron microscopy (SEM), respectively. The hydrogels presented mechanical properties which mimic those of the soft tissues (elastic moduli < 1 MPa), necessary to ensure matrix accommodation and bioadhesion. Maximum swelling capacities were reached by the hydrogels with higher succinic anhydride content at both pH 7.4 (429%) and pH 4.2 (471%), while higher amounts of nystatin released in the simulative immersion media (57% in acidic pH and 51% in pH 7.4) occurred from the physical cross-linked hydrogel. The release mechanism by non-swellable matrix diffusion and the susceptibility of three Candida strains make all the hydrogel formulations effective for NYSm local delivery and for combating fungal infections.

Amphiphilic Chitosan Porous Membranes as Potential Therapeutic Systems with Analgesic Effect for Burn Care

“…In addition, the increase in intensity and slight displacement of primary N – H absorption band indicates that the succinylation reaction occurred at the free NH 2 group of CS with the formation of new amide units – NH – CO – [ 51 ]. The crosslinking process with DS was also confirmed by the disappearance of the epoxy C – H group absorption band from 3055 cm −1 (shown in Figure S4 ) and the appearance of new siloxane (Si – CH 3 ) specific absorption bands at 1252 cm −1 , 839 cm −1 and−778 cm −1 [ 36 ].…”

“…A similar modified chitosan system (in the form of hydrogels and thin films formulations) was investigated by our group in a previous piece of work for the embedment and release of the insoluble antifungal drug nystatin [ 36 ]. In this work, a new approach in the preparation of the chitosan formulation is pursued to fulfill the burns therapeutic system requirements.…”

“…The chitosan membrane without lidocaine (CS-SA/DS-1) spectrum shows absorption bands in accordance with CS chemical modifications. The succinylation of the polysaccharide induced the disappearance of the 3016 cm −1 , 1861 cm −1 and 1773 cm −1 absorption bands (from the SA spectrum— Figure S4 ), following the opening of the anhydride cycle [ 36 ]. In addition, the increase in intensity and slight displacement of primary N – H absorption band indicates that the succinylation reaction occurred at the free NH 2 group of CS with the formation of new amide units – NH – CO – [ 51 ].…”

“…In order to analyze the swelling properties, the experimental data were fitted by using two mathematical models in SCILAB software (version 6.1.0, ESI Group, Rungis, France). Therefore, the pseudo-second order kinetic model (PSO) was applied to investigate the rate of absorbed PBS solution at equilibrium (Equation (5)) and Korsmeyer–Peppas (K–P) adapted kinetic model was used to determine the water diffusion behavior in the polymeric membranes (Equation (6)) [ 39 , 40 ]: where S t1 and S t2 represent the swelling content of the membranes at time t (min), S e1 and S e2 are the equilibrium swelling contents, k s is the second-order constant of the swelling rate, F represents the fractional swelling, k p is a constant dependent on the polymeric matrix structure and n is the diffusion exponential coefficient of the PBS solution into the membranes [ 36 , 39 ].…”

“…Coupled chemical modification of chitosan by acylation with succinic anhydride and crosslinking with an epoxy-terminated disiloxane in order to obtain an amphiphilic matrix was proved in a previous piece of work to be adequate for embedding, and it releases an insoluble antifungal drug [ 36 ]. In this context, the present work proposes deeper investigation of this amphiphilic system by obtaining a novel chitosanthree-dimensional porous membrane, to fulfill all the necessary requirements in burns management, such as: (i) pain relief by solubilization and release of lidocaine; (ii) absorption of large amounts of exudate; (iii) maintaining a moist environment needed for wound healing; (iv) offering protection and covering large areas of injured tissue; and (v) possessing antibacterial activity.…”