Spermidine Cross-Linked Hydrogels as a Controlled Release Biomimetic Approach for Cloxacillin

Abstract

The intrinsic ability of albumin to bind active substances in the physiological fluids has been explored to endow hydrogels with improved capability to regulate drug release. To develop such biomimetic-functional hydrogels, it is critical that albumin conformation is not altered and that the protein remains retained inside the hydrogel keeping its conformational freedom, i.e., it should be not chemically cross-linked. Thus, the hydrogels were prepared with various proportions of albumin by physical cross-linking of anionic polysaccharides (gellan gum and chondroitin sulfate) with the cationic endogen polyamine spermidine under mild conditions in order to prevent albumin denaturation. Texture and swelling properties of hydrogels with various compositions were recorded, and the effect of the preparation variables was evaluated applying neurofuzzy logic tools for hydrogels prepared with and without albumin and associating the antibiotic cloxacillin. Developed hydrogel systems were extensively analyzed by means of nuclear magnetic resonance (NMR) to determine weak-to-medium and strong binding modes and the equilibrium constants of the albumin-cloxacillin association. NMR techniques were also employed to demonstrate the successful modulation of the cloxacillin release from the albumin-containing hydrogels. In vitro microbiological tests carried out with Staphylococcus aureus and Staphylococcus epidermidis confirmed the interest of the albumin-containing hydrogels as efficient platforms for cloxacillin release in its bioactive form.

Matrix-Assisted Regulation of Antimicrobial Properties: Mechanistic Elucidation with Ciprofloxacin-Based Polymeric Hydrogel Against Vibrio Species

“…8,9 Target specificity of these drugs can be further enhanced by molecular modifications with liposomes, micelles, or nanomaterials. 10,11 Efficient derivatization of antibiotics with polymeric material could be a promising alternative for a new class of antibiotics because of the lower toxicity, increased solubility, and prolonged activity originating from polymer antibiotic conjugates (PACs). 12,13 Although there are several reports regarding the potential applications of PACs in detoxification of anticancer drugs such as doxorubicin, 14,15 in therapeutic antibiotic carriers by using degradable 16,17 or nondegradable 18,19 polymer matrices, ittle attention has been paid toward exploring permanently bound polymer antibiotic conjugates on the treatment of bacterial infections.…”

“…High costs for new drug development and stringent approval protocols result in fewer trials of new antimicrobial agents per year. , An alternative path to shorten the time of development for new antimicrobial agents is formulation and derivatization of existing antibiotics with modified functional groups or alteration of charge density, solubility, degradability, selectivity, and efficiency. , Target specificity of these drugs can be further enhanced by molecular modifications with liposomes, micelles, or nanomaterials. , Efficient derivatization of antibiotics with polymeric material could be a promising alternative for a new class of antibiotics because of the lower toxicity, increased solubility, and prolonged activity originating from polymer antibiotic conjugates (PACs). , Although there are several reports regarding the potential applications of PACs in detoxification of anticancer drugs such as doxorubicin, , in therapeutic antibiotic carriers by using degradable , or nondegradable , polymer matrices, ittle attention has been paid toward exploring permanently bound polymer antibiotic conjugates on the treatment of bacterial infections . Introduction of commonly employed polyethylene glycol to several antibiotics moieties like penicillin V, tobramycin or vancomycin can lead to generation of a series of PACs which could exhibit antimicrobial properties against several microorganisms including bacteria.…”

Conjugation of Ciprofloxacin with Poly(2-oxazoline)s and Polyethylene Glycol via End Groups

“…Moreover, formulations based on macromolecules such as nanoparticles, liposomes, or molecular micelles are mostly optimized to change bioavailability. − Another very successful way to prepare efficient derivatives of antibiotics is their combination with polymers. Macromolecules as carriers for therapeutics become increasingly important alternatives because such polymer antibiotic conjugates (PACs) afford lower toxicity, increase solubility, and prolonged activity. , In 2013, two of the top 10 selling drugs in the United States were polymer therapeutics .…”

Advancements in release‐active antimicrobial biomaterials: A journey from release to relief

“…Biocompatible hydrogel scaffold derived from polymers such as chitosan, gelatine, cellulose, and polyethylene glycol (PEG) can accommodate the antibiotics, which are summarized below (Table 1; Casadidio et al, 2018;H. Chen et al, 2017;Das et al, 2015;Grolman et al, 2019;Gustafson et al, 2016;Lakes et al, 2014;L opez-Cebral et al, 2014;Nimal et al, 2016;Özkahraman et al, 2021;Pimenta et al, 2019;Qu et al, 2019;Romero-Montero et al, 2020;Sharma et al, 2019;Sundaram et al, 2018;Vahedi et al, 2018;Yu et al, 2019;Zhang, Qin, et al, 2021).…”