Azithromycin-loaded liposomes and niosomes for the treatment of skin infections: Influence of excipients and preparative methods on the functional properties.

The aim of this study was to develop azithromycin (AZT)-loaded liposomes (LP) and niosomes (NS) useful for the treatment of bacterial skin infections and acne. LP based on phosphatidylcholine from egg yolk (EPC) or from soybean lecithin (SPC), and NS composed of sorbitan monopalmitate (Span 40) or sorbitan monostearate (Span 60) were prepared through the thin film hydration (TFH) and the ethanol injection (EI) methods. The formulations were subsequently characterized for their physico-chemical and functional properties. Vesicles prepared through TFH showed higher average sizes than the corresponding formulations obtained by EI. All the vesicles presented adequate encapsulation efficiency and a negative ζ potential, which assured good stability during the storage period (except for LP-SPC). Formulations prepared with TFH showed a more prolonged AZT release than those prepared through EI, due to their lower surface area and multilamellar structure, as confirmed by atomic force microscopy nanomechanical characterization. Finally, among all the formulations, NS-Span 40-TFH and LP-EPC-TFH allowed the highest drug accumulation in the skin, retained the antimicrobial activity and did not alter fibroblast metabolism and viability. Overall, they could ensure to minimize the dosing and the administration frequency, thus representing promising candidates for the treatment of bacterial skin infections and acne.

A promising eco-sustainable wound dressing based on cellulose extracted from Spartium junceum L. and impregnated with Glycyrrhiza glabra L extract: Design, production and biological properties.

Glycyrrhiza glabra extract is widely known for its antioxidant and anti-inflammatory properties and can improve the wound healing process. The aim of this work was to shorten the time of the healing process by using an eco-sustainable wound dressing based on Spanish broom flexible cellulosic fabric by impregnation with G. glabra extract-loaded ethosomes. Chemical analysis of G. glabra extract was performed by LC-DAD-MS/MS and its encapsulation into ethosomes was obtained using the ethanol injection method. Lipid vesicles were characterized in terms of size, polydispersity index, entrapment efficiency, zeta potential, and stability. In vitro release studies, biocompatibility, and scratch test on 3T3 fibroblasts were performed. Moreover, the structure of Spanish broom dressing and its ability to absorb wound exudate was characterized by Synchrotron X-ray phase contrast microtomography (SR-PCmicroCT). Ethosomes showed a good entrapment efficiency, nanometric size, good stability over time and a slow release of polyphenols compared to the free extract, and were not cytotoxic. Lastly, the results revealed that Spanish broom wound dressing loaded with G. glabra ethosomes is able to accelerate wound closure by reducing wound healing time. To sum up, Spanish broom wound dressing could be a potential new green tool for biomedical applications.

Probiotics, prebiotics and symbiotics in inflammatory bowel diseases: state-of-the-art and new insights.

Inflammatory bowel disease (IBD) consists of two distinct clinical forms, ulcerative colitis (UC) and Crohn's disease (CD), with unknown aetiology, which nevertheless are considered to share almost identical pathophysiological backgrounds. Up to date, a full coherent mechanistic explanation for IBD is still lacking, but people start to realize that the pathogenesis of IBD involves four fundamental components: the environment, gut microbiota, the immune system and the genome. As a consequence, IBD development might be due to an altered immune response and a disrupted mechanism of host tolerance to the non-pathogenic resident microbiota, leading to an elevated inflammatory response. Considering the available data arising from the scientific literature, here reviewed, in CD, a benefit of probiotics remains unproven; in UC, a benefit of probiotics remains unproven, even if E. coli Nissle 1917 seems promising in maintaining remission and it could be considered an alternative in patients intolerant or resistant to 5-ASA preparations; in pouchitis, small controlled trials suggest a benefit from VSL no. 3 in the primary and secondary prevention of pouchitis; in IBD-associated conditions, a benefit of probiotics remains unproven. However, well-designed randomized control clinical trials are necessary to understand the undoubted role of these agents in the management of gut physiology in health and disease.

Mucoadhesive and mucopenetrating chitosan nanoparticles for glycopeptide antibiotic administration.

The use of nanoparticles (NPs) represents a useful strategy for peptide antibiotic delivery to mucosal membranes by either prolonging drug residence time at the target site (mucoadhesive NPs) or by enhancing diffusion across mucus layer to reach the underlying epithelium (mucopenetrating NPs). The purpose of this study was to design chitosan (CH) NPs and to evaluate their employment as mucoadhesive and/or mucopenetrating systems for vancomycin (VM) delivery. NPs were prepared by ionic gelation of CH with sodium carboxymethylcellulose (CMC), sodium alginate (ALG), sodium tripolyphosphate (TPP) or phytic acid (PA) and characterized in terms of size, zeta-potential, morphology, drug encapsulation efficiency, mucoadhesion and mucopenetrating ability. Moreover, in vitro tests were conducted to evaluate VM release and the antibacterial activity against Staphylococcus aureus and Bacillus subtilis. NPs showed sizes ranged from 150 nm to 350 nm with good polydispersity index and positive zeta-potential. The selection of the suitable crosslinker allowed to modulate the mucoadhesive/mucopenetrating properties: CH/TPP NPs showed the best mucoadhesive ability, while CH/PA and CH/CMC NPs were characterized by an improved diffusion across the mucus layer. Further, NPs allowed a fast and complete release of VM, maintaining the antibacterial activity against the tested bacteria species.

[Subfascial endoscopic perforating vein surgery in patients with advanced trophic lesions (lipodermatosclerosis or ulcers)]. / La legatura endoscopica delle vene perforanti nei pazienti con lesione trofiche avanzate(lipodermatosclerosi o ulcere).

AIM: Subfascial endoscopic perforating vein surgery (SEPS) is proposed in the treatment of chronic venous insufficiency stages C4-C6 of the CEAP classification. METHODS: SEPS was performed in 10 patients (4 men, 6 women), 3 of which were stage C4, 4 stage C5 and 3 stage C6. RESULTS: Full resolution of ulcers was achieved in the 12-month follow-up period; no post-operative sepsis complications were observed. CONCLUSIONS: SEPS is a safe procedure and a valuable therapeutic aid in the treatment of chronic venous insufficiency complicated by trophic skin ulcers. Compared with other techniques, it is less invasive, works directly on the healthy skin and significantly reduces skin wounds.

Microparticles based on chitosan/carboxymethylcellulose polyelectrolyte complexes for colon delivery of vancomycin.

The aim of this work was to prepare polyelectrolyte complexes based on chitosan (CH) and carboxymethylcellulose (CMC) for colon delivery of vancomycin (VM). Various batches of polyelectrolyte complexes, using three different CH/CMC weight ratios (3:1, 1:1 and 1:3), were prepared and collected as microparticles by spray-drying process. Microparticles were characterized in terms of yield, encapsulation efficiency, drug loading, morphology and mucoadhesion properties. Microparticles water-uptake and VM release as well as its protection against gastric pepsin degradation were also investigated. Finally, the antibacterial activity against Staphylococcus aureus, a Gram-positive model strain, was evaluated. The best formulation CH/CMC 1:3 was selected based on the encapsulation efficiency, water-uptake and drug release rate. Moreover, microparticles were able to prevent VM degradation and showed a good antibacterial activity against S. aureus. Finally, to improve the release of VM in the colon the selected formulation was coated with lauric acid.

Chitosan based micro- and nanoparticles for colon-targeted delivery of vancomycin prepared by alternative processing methods.

The aim of this work was to prepare chitosan (CH) based particulate formulations for colon delivery of vancomycin (VM). Chitosan microparticles (MPs) and nanoparticles (NPs) loaded with VM were prepared using different CH/tripolyphosphate (TPP) molar ratios and different technological processes. In particular, nanoparticles were prepared by ionic gelation and freeze-drying to recover these particles, or, alternatively, by spray-drying method. Microparticles were prepared using a different spray-dryer. Micro- and nanoparticles were characterized in terms of size distributions by photon correlation spectroscopy (PCS), while encapsulation and drug loading efficiencies were studied using a dialysis method. Fourier Transform Infrared Spectroscopy (FT-IR) was employed to determine the surface composition of the micro- and nanoparticles respectively, and the morphologies of the developed systems were studied by scanning electron microscopy (SEM). Water uptake as well as drug release profiles were also measured. Antibacterial activity against Staphylococcus aureus, a Gram-positive model strain, was evaluated. FT-IR results suggested an electrostatic interaction between VM and CH/TPP particles. Moreover, the particles were found to hold a positive zeta-potential, indicating the presence of CH on the particle surfaces. Particle size and encapsulation efficiency were mainly influenced by the different manufacturing processes employed. Nanoparticles obtained by spray-drying showed the best results in terms of water uptake and drug release rate. Moreover, they showed a good bactericidal activity against S. aureus.

Chitosan/alginate complexes for vaginal delivery of chlorhexidine digluconate.

Chitosan/alginate complexes were prepared at different polycation/polyanion molar ratios and freeze-dried vaginal inserts were obtained for chlorhexidine digluconate local delivery in genital infections. Complex yield, FT-IR spectra, and TGA thermograms were studied to confirm the interaction between the two polyions. The influence of different complexes on physical handling, morphology, and drug distribution in the samples were evaluated by friability test, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS), respectively. In vitro water-uptake, mucoadhesion and release tests were performed as well as microbiological tests toward pathogenic vaginal microorganisms. The results showed that the selection of suitable chitosan/alginate molar ratio and drug loading allowed modulate insert ability to hydrate, adhere to the mucosa, and release chlorhexidine digluconate. The insert containing an excess of alginate was found to be the best performing formulation and showed good antimicrobial activity toward the pathogens Candida albicans and Escherichia coli.