Polysaccharide‐based membranes loaded with erythromycin for application as wound dressings

Abstract

In this study, the antibiotic erythromycin (Ery) was incorporated into chitosan (Ch)-alginate (A) and Ch-xanthan (X) membranes with the aim of using them as bioactive wound dressings. Drug incorporation was performed by direct addition (DA) to the polysaccharide mixture and by membrane impregnation in solution (IS). A higher incorporation efficiency was obtained for DA, but higher amounts of drug were loaded into membranes by the IS method (maxima % 2.1 and 0.7 g/g for Ch-X and Ch-A, respectively) because the initial concentration of drug could be higher than that in the DA method. Ery release in phosphate-buffered saline was slow, reaching about 12 and 32 mg of drug/g of membrane in 60 h for Ch-X and 4 and 16 mg/g for Ch-A by the DA and IS methods, respectively. With formulations prepared with IS, the required therapeutic dosage was reached within 60 h, whereas for those incorporating the drug by DA, prolonged use would be required. Both membrane types behaved as drug reservoirs, providing continuous antibiotic release to the wound site. Formulations with higher drug contents showed effective antibacterial activity against two species of bacteria commonly found in skin lesions, Staphylococcus aureus and Pseudomonas aeruginosa, and were thus potentially capable of protecting the wound site from bacterial attack.Erythromycin (Ery) is a medium-spectrum antibiotic of the macrolide family and is produced by Streptomyces erythreus. 6 Susceptible microorganisms include aerobic Gram-positive bacteria, Gram-negative cocci, spirochetes, actinomycetes, rickettsia, Chlamydia trachomatis, Mycoplasma pneumoniae, Legionella pneumophila, nontuberculous mycobacteria, and some anaerobic bacteria. 7 This antibiotic consists of a 13-carbon ring with two sugars attached by glycosidic linkages 8,9 (Figure 1) and has a molecular weight of 733.9 Da. It is slightly soluble in water and very soluble in organic solvents such as ethanol 10 ; it is useful in the therapy of pneumonia, diphtheria, whooping cough, urethritis, and erythrasma and acne treatments. 7 For topical administration, the common dosage is 20 mg/g of vehicle. 11The incorporation of Ery into wound dressings is of interest if prolonged protection and drug delivery are simultaneously desired, mostly for extensive and painful lesions of difficult manipulation. These systems show improved therapy efficiency by means of an appropriate release profile; this leads to drug availability at the wound site for long periods and, thereby, reduces the need for repeated administrations. 12The main purpose of using a wound dressing is to provide a suitable environment at the wound site so that healing is fast

Analysis of the performance of polysaccharide membranes in aqueous media as a tool to assist wound‐dressing selection

“…When wet, all of the membranes were highly transparent and capable of easily adjusting to the body's contours [ Figure 1 , which also showed fibers on its surface. The same behavior was observed by Souza et al 42 Conversely, the Ch-G membranes had a dense structure and a rather smooth surface [ Figure 1(I)], as reported previously by Souza et al 49 Souza et al 42 proposed a mechanism for the organization of Ch-A and Ch-X membranes in lamellar structures on the basis of the interactions that stabilize the final PEC structure. The formation of this structure involves three steps.…”

“…The same behavior was observed by Souza et al 42 Conversely, the Ch-G membranes had a dense structure and a rather smooth surface [ Figure 1(I)], as reported previously by Souza et al 49 Souza et al 42 proposed a mechanism for the organization of Ch-A and Ch-X membranes in lamellar structures on the basis of the interactions that stabilize the final PEC structure. 14,50 Souza et al 42 stated that the lamellae were probably a result of the spacing between secondary complexes, as a consequence of local mild, but multiple hydrophobic interactions, and they occurred for both the Ch-A and Ch-X matrixes. 14 The first step refers to primary complex formation, in which Coulomb forces between the two polyelectrolytes are involved.…”

“…[Color figure can be viewed at wileyonlinelibrary.com] ARTICLE WILEYONLINELIBRARY.COM/APPCh-X membranes,42 FTIR analysis corroborated the formation of PECs among the polymers through interactions between the amino groups of chitosan and the carboxyl groups of alginate and xanthan gum. [Color figure can be viewed at wileyonlinelibrary.com] ARTICLE WILEYONLINELIBRARY.COM/APPCh-X membranes,42 FTIR analysis corroborated the formation of PECs among the polymers through interactions between the amino groups of chitosan and the carboxyl groups of alginate and xanthan gum.…”

“…35 Xanthan gum, on the other hand, is produced by Xanthomonas campestris, and presents a branched structure formed by repeated pentasaccharide blocks (two glucoses, two mannoses, and one glucuronic acid unit, with a pK a close to 4.6) with a main chain consisting of ß-D-glucose units linked at the 1 and 4 positions. Souza et al 42 evaluated the activity of chitosan and alginate or xanthan gum membranes against the same bacteria and also observed no antibacterial activity in either formulation. 24,38 This polymer is extracted from the seeds of Cyamopsis tetragonolobus, and its structure consists of a linear chain of Dmannopyranose residues to which, on average, every alternate mannose, a D-galactopyranose residue, is linked.…”

Antibacterial wound dressing nanofibrous mats composed of cellulose acetate loaded with chitosan/erythromycin nanoparticles

“…Erythromycin (Ery), is a medium-spectrum antibiotic, achieved by Streptomyces erythreus that contains a 13-carbon ring with two sugars involved by glycosidic linkages (Scheme 1c) [30,31]. It is very soluble in organic solvents and poorly soluble in water; it is valuable in the remedy of pneumonia, diphtheria, whooping cough, and acne handlings [30][31][32]. The common dosage for topical administration is about 20 mg/g [33].…”