Gellan gum spongy-like hydrogel-based dual antibiotic therapy for infected diabetic wounds.

Diabetic foot infection (DFI) is an important cause of morbidity and mortality. Antibiotics are fundamental for treating DFI, although bacterial biofilm formation and associated pathophysiology can reduce their effectiveness. Additionally, antibiotics are often associated with adverse reactions. Hence, improved antibiotic therapies are required for safer and effective DFI management. On this regard, drug delivery systems (DDSs) constitute a promising strategy. We propose a gellan gum (GG)-based spongy-like hydrogel as a topical and controlled DDS of vancomycin and clindamycin, for an improved dual antibiotic therapy against methicillin-resistant Staphylococcus aureus (MRSA) in DFI. The developed DDS presents suitable features for topical application, while promoting the controlled release of both antibiotics, resulting in a significant reduction of in vitro antibiotic-associated cytotoxicity without compromising antibacterial activity. The therapeutic potential of this DDS was further corroborated in vivo, in a diabetic mouse model of MRSA-infected wounds. A single DDS administration allowed a significant bacterial burden reduction in a short period of time, without exacerbating host inflammatory response. Taken together, these results suggest that the proposed DDS represents a promising strategy for the topical treatment of DFI, potentially overcoming limitations associated with systemic antibiotic administration and minimizing the frequency of administration.

Development of an antibiotics delivery system for topical treatment of the neglected tropical disease Buruli ulcer.

Skin infection by Mycobacterium ulcerans causes Buruli ulcer (BU) disease, a serious condition that significantly impact patient' health and quality of life and can be very difficult to treat. Treatment of BU is based on daily systemic administration of antibiotics for at least 8 weeks and presents drawbacks associated with the mode and duration of drug administration and potential side effects. Thus, new therapeutic strategies are needed to improve the efficacy and modality of BU therapeutics, resulting in a more convenient and safer antibiotic regimen. Hence, we developed a dual delivery system based on poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) microparticles and a gellan gum (GG) hydrogel for delivery of rifampicin (RIF) and streptomycin (STR), two antibiotics used for BU treatment. RIF was successfully loaded into PHBV microparticles, with an encapsulation efficiency of 43%, that also revealed a mean size of 10 µm, spherical form and rough topography. These microparticles were further embedded in a GG hydrogel containing STR. The resultant hydrogel showed a porous microstructure that conferred a high water retention capability (superior to 2000%) and a controlled release of both antibiotics. Also, biological studies revealed antibacterial activity against M. ulcerans, and a good cytocompatibility in a fibroblast cell line. Thus, the proposed drug delivery system can constitute a potential topical approach for treatment of skin ulcers caused by BU disease.

Comparing deep eutectic solvents and cyclodextrin complexes as curcumin vehicles for blue-light antimicrobial photodynamic therapy approaches.

Curcumin (Cur), a polyphenolic compound derived from Curcuma longa L., has garnered the attention of the scientific community due to its remarkable biological properties such as its potential as a photosensitizing agent for photodynamic therapy (PDT). However, due to its low solubility in aqueous media and instability at physiological and alkaline pH, Cur has struggled to find relevant clinical application. To tackle these shortcomings, two distinct Cur-based formulations based on either complexation with methyl-ß-cyclodextrin (MßCD), MßCDC-Cur, or dissolution in a choline chloride (ChCl): glycerol (Gly) deep eutectic solvent (DES), DES-Cur, were produced, physio-chemically characterized and compared regarding their potential as phototherapeutic agents for blue-light antimicrobial photodynamic therapy (aPDT) approaches. Both MßCD-Cur and DES-Cur were able to greatly enhance Cur solubility profile when compared to Cur powder. However, MßCD-Cur appears to hinder some of Cur's basal biological properties and possessed greater basal cytotoxicity towards L929 murine fibroblast cell line. Furthermore, MßCD-Cur was less photo-responsive when exposed to light which may hamper its application in blue-light aPDT approaches. In contrast, DES-Cur showed good biological properties and high photoresponsivity, displaying relevant phototoxicity against bacterial pathogens (≥ 99.9% bacterial reduction) while being better tolerated by L929 murine cells. Overall, this study found DES to be the more effective vehicle for Cur in terms of phototherapeutic potential which will serve as basis to develop novel platforms and approaches for blue-light aPDT targeting localized superficial infections.

Surface Functionalization of Ureteral Stents-Based Polyurethane: Engineering Antibacterial Coatings.

Bacterial colonization of polyurethane (PU) ureteral stents usually leads to severe and challenging clinical complications. As such, there is an increasing demand for an effective response to this unmet medical challenge. In this study, we offer a strategy based on the functionalization of PU stents with chitosan-fatty acid (CS-FA) derivatives to prevent bacterial colonization. Three different fatty acids (FAs), namely stearic acid (SA), oleic acid (OA), and linoleic acid (LinA), were successfully grafted onto chitosan (CS) polymeric chains. Afterwards, CS-FA derivatives-based solutions were coated on the surface of PU stents. The biological performance of the modified PU stents was evaluated against the L929 cell line, confirming negligible cytotoxicity of the developed coating formulations. The antibacterial potential of coated PU stents was also evaluated against several microorganisms. The obtained data indicate that the base material already presents an adequate performance against Staphylococcus aureus, which slightly improved with the coating. However, the performance of the PU stents against Gram-negative bacteria was markedly increased with the surface functionalization approach herein used. As a result, this study reveals the potential use of CS-FA derivatives for surface functionalization of ureteral PU stents and allows for conjecture on its successful application in other biomedical devices.

A Fibrin Coating Method of Polypropylene Meshes Enables the Adhesion of Menstrual Blood-Derived Mesenchymal Stromal Cells: A New Delivery Strategy for Stem Cell-Based Therapies.

Polypropylene (PP) mesh is well-known as a gold standard of all prosthetic materials of choice for the reinforcement of soft tissues in case of hernia, organ prolapse, and urinary incontinence. The adverse effects that follow surgical mesh implantation remain an unmet medical challenge. Herein, it is outlined a new approach to allow viability and adhesion of human menstrual blood-derived mesenchymal stromal cells (MenSCs) on PP surgical meshes. A multilayered fibrin coating, based on fibrinogen and thrombin from a commercial fibrin sealant, was optimized to guarantee a homogeneous and stratified film on PP mesh. MenSCs were seeded on the optimized fibrin-coated meshes and their adhesion, viability, phenotype, gene expression, and immunomodulatory capacity were fully evaluated. This coating guaranteed MenSC viability, adhesion and did not trigger any change in their stemness and inflammatory profile. Additionally, MenSCs seeded on fibrin-coated meshes significantly decreased CD4+ and CD8+ T cell proliferation, compared to in vitro stimulated lymphocytes (p < 0.0001). Hence, the proposed fibrin coating for PP surgical meshes may allow the local administration of stromal cells and the reduction of the exacerbated inflammatory response following mesh implantation surgery. Reproducible and easy to adapt to other cell types, this method undoubtedly requires a multidisciplinary and translational approach to be improved for future clinical uses.

Use of hemostatic agents for surgical bleeding in laparoscopic partial nephrectomy: Biomaterials perspective.

In recent years, there was an abrupt increase in the incidence of renal tumors, which prompt up the appearance of cutting-edge technology, including minimally invasive and organ-preserving approaches, such as laparoscopic partial nephrectomy (LPN). LPN is an innovative technique used to treat small renal masses that have been gaining popularity in the last few decades due to its promissory results. However, the bleeding control remains the main challenge since the majority of currently available hemostatic agents (HAs) used in other surgical specialities are inefficient in LPN. This hurried the search for effective HAs adapted for LPN surgical peculiarities, which resulted on the emergence of different types of topical HAs. The most promising are the natural origin HAs because of their inherent biodegradability, biocompatibility, and lowest toxicity. These properties turn them top interests' candidates as HAs in LPN. In this review, we present a deep overview on the progress achieved in the design of HAs based on natural origin polymers, highlighting their distinguishable characteristics and providing a clear understanding of their hemostat's role in LPN. This way it may be possible to establish a structure-composition properties relation, so that novel HAs for LPN can be designed to explore current unmet medical needs.

In vitro bioactivity studies of ceramic structures isolated from marine sponges.

In this work, we focused on the potential of bioceramics from different marine sponges-namely Petrosia ficiformis, Agelas oroides and Chondrosia reniformis-for novel biomedical/industrial applications. The bioceramics from these sponges were obtained after calcination at 750 °C for 6 h in a furnace. The morphological characteristics were evaluated by scanning electron microscopy (SEM). The in vitro bioactivity of the bioceramics was evaluated in simulated body fluid (SBF) after 14 and 21 d. Observation of the bioceramics by SEM after immersion in SBF solution, coupled with spectroscopic elemental analysis (EDS), showed that the surface morphology was consistent with a calcium-phosphate (Ca/P) coating, similar to hydroxyapatite crystals (HA). Evaluation of the characteristic peaks of Ca/P crystals by Fourier transform infrared spectroscopy and x-ray diffraction further confirmed the existence of HA. Cytotoxicity studies were carried out with the different ceramics and these were compared with a commercially available Bioglass(®). In vitro tests demonstrated that marine bioceramics from these sponges are non-cytotoxic and have the potential to be used as substitutes for synthetic Bioglass(®).

Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems.

A therapeutic deep eutectic system (THEDES) is here defined as a deep eutectic solvent (DES) having an active pharmaceutical ingredient (API) as one of the components. In this work, THEDESs are proposed as enhanced transporters and delivery vehicles for bioactive molecules. THEDESs based on choline chloride (ChCl) or menthol conjugated with three different APIs, namely acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA), were synthesized and characterized for thermal behaviour, structural features, dissolution rate and antibacterial activity. Differential scanning calorimetry and polarized optical microscopy showed that ChCl:PA (1:1), ChCl:AA (1:1), menthol:AA (3:1), menthol:BA (3:1), menthol:PA (2:1) and menthol:PA (3:1) were liquid at room temperature. Dissolution studies in PBS led to increased dissolution rates for the APIs when in the form of THEDES, compared to the API alone. The increase in dissolution rate was particularly noticeable for menthol-based THEDES. Antibacterial activity was assessed using both Gram-positive and Gram-negative model organisms. The results show that all the THEDESs retain the antibacterial activity of the API. Overall, our results highlight the great potential of THEDES as dissolution enhancers in the development of novel and more effective drug delivery systems.

Design of controlled release systems for THEDES-Therapeutic deep eutectic solvents, using supercritical fluid technology.

Deep eutectic solvents (DES) can be formed by bioactive compounds or pharmaceutical ingredients. A therapeutic DES (THEDES) based on ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), and menthol was synthesized and its thermal behavior was analyzed by differential scanning calorimetry (DSC). A controlled drug delivery system was developed by impregnating a starch:poly-ϵ-caprolactone polymeric blend (SPCL 30:70) with the menthol:ibuprofen THEDES in different ratios (10 and 20 wt%), after supercritical fluid sintering at 20 MPa and 50 °C. The morphological characterization of SPCL matrices impregnated with THEDES was performed by scanning electron microscopy (SEM) and micro-computed tomography (micro-CT). Drug release studies were carried out in a phosphate buffered saline. The results obtained provide important clues for the development of carriers for the sustainable delivery of bioactive compounds.

Isolation of friedelin from black condensate of cork.

Black condensates (BC) are wastes of the insulation corkboard industry that contain several valuable chemicals, including friedelin, a terpene exhibiting biological activity. Herein, we report a straightforward procedure to extract friedelin from BC. Using this procedure, we were able to extract friedelin with yields between 0.4% and 2.9% and to further purify it obtaining purities from 77.0% to 99.3% (HPLC). The initial BC (2 batches), extracted raw product and purified friedelin were analyzed using FTIR. The extraction yields and purities were found to be directly related to the intensity of the carbonyl vibration at 1713 cm(-1) in the FTIR spectrum of the used BC batch. Therefore, these spectra can be used to screen and select BC batches suitable for friedelin extraction.