Calcitermin-Loaded Smart Gels Activity against Candida albicans: A Preliminary In Vitro Study

Abstract

Calcitermin is an antimicrobial peptide of 15 amino acids found in human nasal fluid characterized by antifungal and antibacterial properties. Candida albicans is the most common human fungal pathogen affecting many tissues, such as vaginal mucosa. In this study a formulation suitable for calcitermin administration on vaginal mucosa was developed for the treatment of fungal infections. To favor topical application, mucosal adhesion, and permanence, gels based on poloxamer 407 and xanthan gum were designed and compared with regard to their rheological behavior, erosion, and leakage. The selected gel was loaded with calcitermin, whose release kinetic was evaluated in vitro by Franz cells. An antifungal activity assay was conducted to assess the calcitermin anticandidal potential and the effect of its inclusion in the selected gel. The rheological study revealed the elastic and viscous moduli behavior as a function of poloxamer 407 and xanthan gum concentration. Xanthan gum presence decreased the transition temperature of the gel, while prolonging its erosion and leakage. Particularly, poloxamer 407, 18% and xanthan gum 0.4% were chosen. The calcitermin loading in the selected gel resulted in a transparent and homogeneous formulation and in a 4-fold decrease of the release rate with respect to the calcitermin solution, as evidenced by Franz cell study. The anticandidal activity tests demonstrated that calcitermin-loaded gel was more active against Candida albicans with respect to the peptide solution.

In Situ Gelling Behavior and Biopharmaceutical Characterization of Nano-Silver-Loaded Poloxamer Matrices Designed for Nasal Drug Delivery

“…The thermo-sensitive Poloxamer 407 (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer)—P407—was selected as the main constituent in the composition of in situ gelling nasal spray for protection against respiratory infections. The polymer is known for its low toxicity, good tolerability, great chemical inertness, and drug–polymer compatibility [ 2 , 10 ]; because of its amphiphilic nature, P407 self-assembles into micelles, which aggregate with the increase in temperature and forms a crystal network (micelles order into a hexagonal crystalline packing and form a solid gel) [ 11 , 12 ]. The gelation temperature (T g ) of P407 solutions depends on the polymer’s concentration and the presence of additives such as active pharmaceutical ingredients and excipients [ 11 ]; in any case, the gelation of P407 ≥ 15 w / w % aqueous solutions occurs in a temperature range appropriate for biomedical applications [ 13 , 14 ].…”

Metal coordination governs the antimicrobial efficacy of calcitermin derivatives

“…13 The lowering of the pH value contributes to the protonation of the three histidine residues, thus favouring the interaction of calcitermin with the negatively charged groups present on the surface of bacterial cells. 12,14,15 A systematic study was undertaken on calcitermin derivatives obtained by introducing modifications in the amino acid sequence of the native peptide, with the aim of studying their impact on the stability in plasma, metal coordination and antimicrobial activity of the peptide. Previous studies carried out on metal-chelating peptides have highlighted that the presence of serine residues in the proximity of coordinated histidines favours the binding of the backbone N-amides by copper ions, affecting the complex formation ability of the investigated systems and generally increasing the Cu 2+ binding affinity.…”

“…Ala-to-Ser substitutions are introduced with the aim of verifying their impact on metal coordination, and whether this can affect the antimicrobial activity of calcitermin. [19][20][21][22][23][24] Metal coordination and antimicrobial properties have also been investigated for the calcitermin variant truncated between positions 7 and 8 and protected at the amino and carboxyl termini (Ac-AHYHTHKE-NH 2 , WT (8)(9)(10)(11)(12)(13)(14)(15)). Compared to wild-type calcitermin, in WT (8)(9)(10)(11)(12)(13)(14)(15) the more lipophilic portion of the molecule, not directly involved in metal coordination, was excluded in order to clarify whether the coordination site -HYHTH-is sufficient to form Cu 2+ and Zn 2+ complexes with microbicidal activity.…”

Polymer-Based Hydrogels Applied in Drug Delivery: An Overview

“…By incorporating specific bioactive molecules or sensors into the hydrogel network, changes in the surrounding environment [16,17,29], such as the presence of target analytes, can be detected and transduced into measurable signals [81,104,105]. This capability opens up opportunities for the development of diagnostic platforms [11,83,106], implantable biosensors [13,15,69,107,108], and smart drug delivery systems [11,56,109].…”