Gelatin Matrices Research Articles

Development of novel carboxymethyl cellulose/gelatin-based edible films with pomegranate peel extract as antibacterial/antioxidant agents for beef preservation

Novel antioxidant and antibacterial composite films were fabricated by incorporating pomegranate peel extract (PPE) into gelatin and carboxymethyl cellulose matrices. Increasing PPE concentration significantly (p < 0.05) altered physical properties and improved UV (decrease in light transmission 87.30 % to 9.89 % at 400 nm) and water resistance, while FTIR and molecular docking results revealed hydrogen bonding between PPE and film matrix. PPE incorporation enhanced antioxidant activity up to 84.15 ± 0.12 % and also restricted gram-positive and gram-negative bacterial growth by 72.4 % and 65.9 % respectively after 24 h, measured by antimicrobial absorption assays. For beef packaging applications at refrigeration temperatures, PPE films were most effective at extending shelf-life up to 3 days, as evidenced by reduced total viable counts, total volatile basic nitrogen, weight loss, and pH changes compared to control films. Therefore, these antioxidant and antibacterial films have potential applications in food packaging to protect against mechanical stress, light exposure, microbial spoilage, and oxidative free radicals.

Adeno-associated virus vector hydrogel formulations for brain cancer gene therapy applications

Gelatin-based formulations are utilized in neurosurgical procedures, with Medisponge® serving as an illustration of a secure and biocompatible hemostatic formulation. Noteworthy are combined hemostatic products that integrate pharmacological agents with gelatin. Gelatin matrices, which host biologically active substances, provide a platform for a variety of molecules. Biopolymers function as carriers for chemicals and genes, a facet particularly pertinent in brain cancer therapy, as gene therapy complement conventional approaches. The registration of Zolgensma underscores the efficacy of rAAV vectors in therapeutic gene delivery to the CNS. rAAVs, renowned for their safety, stability, and neuron-targeting capabilities, predominate in CNS gene therapy studies. The effectiveness of rAAV vector therapy varies based on the serotype and administration route. Local gene therapy employing hydrogel (e.g., post-tumor resection) enables the circumvention of the blood-brain barrier and restricts formulation diffusion. This study formulates gelatin rAAV gene formulations and evaluates vector transduction potential. Transduction efficiency was assessed using ex vivo mouse brains and in vitro cancer cell lines. In vitro, the transduction of rAAV vectors in gelatin matrices was quantified through qPCR, measuring the itr and Gfp expression. rAAVDJ and rAAV2 demonstrated superior transduction in ex vivo and in vitro models. Among the cell lines tested (Hs683, B16-F10, NIH:OVCAR-3), gelatin matrix F1 exhibited selective transduction, particularly with Hs683 human glioma cells, surpassing the performance Medisponge®. This research highlights the exploration of local brain cancer therapy, emphasizing the potential of gelatin as an rAAV vector carrier for gene therapy. The functional transduction activity of gelatin rAAV formulations is demonstrated.

Embryonic Stem Cells Can Generate Oral Epithelia under Matrix Instruction.

We aimed to investigate whether molecular clues from the extracellular matrix (ECM) can induce oral epithelial differentiation of pluripotent stem cells. Mouse embryonic stem cells (ESC) of the feeder-independent cell line E14 were used as a model for pluripotent stem cells. They were first grown in 2D on various matrices in media containing vitamin C and without leukemia inhibitory factor (LIF). Matrices investigated were gelatin, laminin, and extracellular matrices (ECM) synthesized by primary normal oral fibroblasts and keratinocytes in culture. Differentiation into epithelial lineages was assessed by light microscopy, immunocytochemistry, and flow cytometry for cytokeratins and stem cell markers. ESC grown in 2D on various matrices were afterwards grown in 3D organotypic cultures with or without oral fibroblasts in the collagen matrix and examined histologically and by immunohistochemistry for epithelial (keratin pairs 1/10 and 4/13 to distinguish epidermal from oral epithelia and keratins 8,18,19 to phenotype simple epithelia) and mesenchymal (vimentin) phenotypes. ECM synthesized by either oral fibroblasts or keratinocytes was able to induce, in 2D cultures, the expression of cytokeratins of the stratified epithelial phenotype. When grown in 3D, all ESC developed into two morphologically distinct cell populations on collagen gels: (i) epithelial-like cells organized in islands with occasional cyst- or duct-like structures and (ii) spindle-shaped cells suggestive of mesenchymal differentiation. The 3D culture on oral fibroblast-populated collagen matrices was necessary for further differentiation into oral epithelia. Only ESC initially grown on 2D keratinocyte or fibroblast-synthesized matrices reached full epithelial maturation. In conclusion, ESC can generate oral epithelia under matrix instruction.

Advances in Gelatin Bioinks to Optimize Bioprinted Cell Functions.

Gelatin is a widely utilized bioprinting biomaterial due to its cell-adhesive and enzymatically cleavable properties, which improve cell adhesion and growth. Gelatin is often covalently cross-linked to stabilize bioprinted structures, yet the covalently cross-linked matrix is unable to recapitulate the dynamic microenvironment of the natural extracellular matrix (ECM), thereby limiting the functions of bioprinted cells. To some extent, a double network bioink can provide a more ECM-mimetic, bioprinted niche for cell growth. More recently, gelatin matrices are being designed using reversible cross-linking methods that can emulate the dynamic mechanical properties of the ECM. This review analyzes the progress in developing gelatin bioink formulations for 3D cell culture, and critically analyzes the bioprinting and cross-linking techniques, with a focus on strategies to optimize the functions of bioprinted cells. This review discusses new cross-linking chemistries that recapitulate the viscoelastic, stress-relaxing microenvironment of the ECM, and enable advanced cell functions, yet are less explored in engineering the gelatin bioink. Finally, this work presents the perspective on the areas of future research and argues that the next generation of gelatin bioinks should be designed by considering cell-matrix interactions, and bioprinted constructs should be validated against currently established 3D cell culture standards to achieve improved therapeutic outcomes.

Perspectives on the Use of Biopolymeric Matrices as Carriers for Plant-Growth Promoting Bacteria in Agricultural Systems.

The subject of this review is to discuss some aspects related to the use of biopolymeric matrices as carriers for plant-growth promoting bacteria (PGPB) in agricultural systems as a possible technological solution for the establishment of agricultural production practices that result in fewer adverse impacts on the environment, reporting some promising and interesting results on the topic. Results from the encapsulation of different PGPB on alginate, starch, chitosan, and gelatin matrices are discussed, systematizing some advances made in this area of knowledge in recent years. Encapsulation of these bacteria has been shown to be an effective method for protecting them from unsuitable environments, and these new products that can act as biofertilizers and biopesticides play an important role in the establishment of a sustainable and modern agriculture. These new products are technological solutions for replacing deleterious chemical fertilizers and pesticides, maintaining soil fertility and stability, and improving crop productivity and food security. Finally, in the near future, scale-up studies will have to provide new information about the large-scale production of these materials as well as their application in the field under different biotic and abiotic stress conditions.

Invadopodia Methods: Detection of Invadopodia Formation and Activity in Cancer Cells Using Reconstituted 2D and 3D Collagen-Based Matrices.

Tumor dissemination involves cancer cell migration through the extracellular matrix (ECM). ECM is mainly composed of collagen fibers that oppose cell invasion. To overcome hindrance in the matrix, cancer cells deploy a protease-dependent program in order to remodel the matrix fibers. Matrix remodeling requires the formation of actin-based matrix/plasma membrane contact sites called invadopodia, responsible for collagen cleavage through the accumulation and activity of the transmembrane type-I matrix metalloproteinase (MT1-MMP). In this article, we describe experimental procedures designed to assay for invadopodia formation and for invadopodia activity using 2D and 3D models based on gelatin (denatured collagen) and fibrillar type-I collagen matrices.

Anionic polymers amplify electrokinetic perfusion through extracellular matrices.

Electrical stimulation (ES) promotes healing of chronic epidermal wounds and delays degeneration of articular cartilage. Despite electrotherapeutic treatment of these non-excitable tissues, the mechanisms by which ES promotes repair are unknown. We hypothesize that a beneficial role of ES is dependent on electrokinetic perfusion in the extracellular space and that it mimics the effects of interstitial flow. In vivo, the extracellular space contains mixtures of extracellular proteins and negatively charged glycosaminoglycans and proteoglycans surrounding cells. While these anionic macromolecules promote water retention and increase mechanical support under compression, in the presence of ES they should also enhance electro-osmotic flow (EOF) to a greater extent than proteins alone. To test this hypothesis, we compare EOF rates between artificial matrices of gelatin (denatured collagen) with matrices of gelatin mixed with anionic polymers to mimic endogenous charged macromolecules. We report that addition of anionic polymers amplifies EOF and that a matrix comprised of 0.5% polyacrylate and 1.5% gelatin generates EOF with similar rates to those reported in cartilage. The enhanced EOF reduces mortality of cells at lower applied voltage compared to gelatin matrices alone. We also use modeling to describe the range of thermal changes that occur during these electrokinetic experiments and during electrokinetic perfusion of soft tissues. We conclude that the negative charge density of native extracellular matrices promotes electrokinetic perfusion during electrical therapies in soft tissues and may promote survival of artificial tissues and organs prior to vascularization and during transplantation.

Development of gelatin/PVA based colorimetric films with a wide pH sensing range winery solid by-product (Vinasse) for monitor shrimp freshness

Anthocyanins were extracted from a winery solid by-product (Vinasse) and added to fish gelatin (FG) and polyvinyl alcohol (PVA) matrices to create freshness monitoring labels. Three different colorimetric indicator smart films [PWE = polyvinyl alcohol with wine extract (WE), FWE = fish gelatin with WE, and PFWE = polyvinyl alcohol and FG blended film with WE] were generated and examined for their suitability to monitor the freshness of shrimp. The mechanical and optical properties, ammonia sensitivity, and colorimetric analysis of smart films were determined. Fourier transform-infrared spectroscopy (FTIR) was used to evaluate the interaction of anthocyanins with FG and PVA and changes in the film's chemical composition with storage. The film surfaces were characterized with atomic force microscopy (AFM). The incorporation of WE enhanced the films' flexibility by providing plasticizer and surfactant properties. The PWE film showed the best color stability. The FWE film showed the least amount of total color change with exposure to ammonia gas and was deemed suitable for refrigerated food packaging. The color of all indicator films showed significant changes suggesting that PWE, FWE, and PFWE films can be utilized in the intelligent packaging application for protein-rich foods to detect spoilage.

Investigating the Ovarian Microstructure in the Genera Helicolenus and Scorpaena (Teleostei, Sub-Order Scorpaenoidei) with Implications for Ovarian Dynamics and Spawning.

Simple SummaryThe diversity of reproductive mechanism in bony fishes is greater than in any other group of vertebrates. It ranges from oviparous, to several stages of viviparous forms. In this context, scorpaenoid fishes belonging to the families Scorpaenidae and Sebastidae are of particular interest, since they show extremely varied reproductive modes connected with ovarian structures. We describe here the ovarian morphology of five rockfish species showing different reproductive modalities, using histology. Specialized microscopic features were found during gametogenesis, strictly related to the production of gelatinous mass surrounding the eggs, typical of these species. Based on microscopic maturity stages here analyzed, we found that all species shed eggs more than once through the spawning season, and were characterized by continuous oogenesis with multiple oocyte deposition. Further ovarian dynamic observations supported the hypothesis that all species had an indeterminate fecundity.The sub-order Scorpenoidei appears to be particularly interesting due to the presence of intermediate stages between oviparity and viviparity in several species. The present study aims to describe the ovarian morphology, using a histological and histochemical approach, in four ovuliparous species belonging to Scorpaena genus compared with a zygoparous species, H. dactylopterus, focusing also on the assessment of the ovarian dynamics in the populations of such species in Sardinia waters (central–western Mediterranean). Ovarian sections of all species were examined using light microscopy. All species showed a specialized ovary, cystovarian type II-3, strictly related to the production of gelatinous matrices surrounding the eggs. Some microscopic peculiarities in the oogenesis process were found: thin zona pellucida, small and low cortical alveoli, and a specialized ovarian wall during the spawning period. All species analyzed were batch-spawners with an asynchronous ovarian organization. A continuous recruitment of oocytes and the occurrence of de novo vitellogenesis was also observed. During the spawning period, low atresia intensity was detected, while a marked increase in this intensity found in the ovaries at the end of spawning season. Our observations may support an indeterminate fecundity type for these species.

Analysis of Swelling Capability and Efficacy of Gelatin‐Based Antibiotic Eluting Hemostatic Agents

During surgical procedures, hemostatic agents are applied within incisions to accelerate the clotting process and mitigate excessive blood loss. These hemostats are typically gelatin based and remain within the surgical site after the incision is closed, which can serve as an ideal environment for microbial growth. Therefore, we developed a gelatin‐based hemostatic agent capable of sustained release of antibiotics to serve as a prophylactic measure against surgical site infections, while avoiding the disadvantages associated with systemic antibiotic administration. Gelatin matrices containing trapped/covalently bonded antibiotics were generated using type B gelatin, the cross‐linking agent 1‐ethyl‐3‐(‐3‐dimethylaminopropyl)carbodiimide, and either vancomycin, ciprofloxacin, or ceftazidime. Gelatin matrices were allowed to elute antibiotics over time in phosphate‐buffered saline solution to simulate release under native conditions, and elution samples were analyzed via infrared spectroscopy, Kirby‐Bauer, microdilution, and cell viability assays. Temporal swelling assays were also performed to assess the swelling capacity of the antibiotic‐eluting matrices. Eluted antibiotics retained structural integrity as demonstrated with infrared spectroscopy. Vancomycin and ciprofloxacin‐containing matrices inhibited microbial growth, while ceftazidime matrices exhibited no significant difference in inhibition when compared to controls. The antibiotic‐eluting matrices maintained their biocompatibility, as evaluated by cell viability assays. In addition, temporal swelling assays affirmed the ability of the matrices to perform as viable hemostats. Thus, adoption of these antibiotic‐eluting hemostatic agents in surgical practice could result in a novel method of combating surgical site infections while avoiding drawbacks associated with systemic antibiotic administration.

Effect of gelatin type on the structure and properties of microfibrillated cellulose reinforced gelatin edible films

AbstractThe physical and mechanical properties of gelatin edible films need to be significantly improved to meet the increasing requirements of food and pharmaceutical industry. This study investigates the effect of gelatin type on the structure and properties of glycerol plasticized gelatin films reinforced by microfibrillated cellulose (MFC). Results indicate that the tensile strength of type‐A and type‐B gelatin (GelA and GelB) films increases by 48% and 90% respectively at an optimum MFC content of 15 wt% in comparison to control gelatin films without MFC. The incorporation of MFC also has a more pronounced impact on optical properties and moisture absorption capability of GelB films than on those of GelA films. Scanning electron microscopy and polarized optical microscopy studies show that the MFC fibrils are uniformly distributed in both types of gelatin matrices. X‐ray diffraction and attenuated total reflectance‐Fourier transform infrared analyses reveal that the interactions between MFC and GelB are stronger than those of between the MFC and GelA. The mechanism behind the more significant mechanical performance improvement of GelB films by the addition of MFC is speculated to be that stronger hydrogen bonding interactions contribute to enhanced structural integrity and stability of the gelatin‐based films.

Long-term maintenance of functional primary human hepatocytes in 3D gelatin matrices produced by solution blow spinning

Solution blow spinning (SBS) has recently emerged as a novel method that can produce nano- and microfiber structures suitable for tissue engineering. Gelatin is an excellent precursor for SBS as it is derived mainly from collagens that are abundant in natural extracellular matrices. Here we report, for the first time the successful generation of 3D thermally crosslinked preforms by using SBS from porcine gelatin. These SBS mats were shown to have three-dimensional fibrous porous structure similar to that of mammalian tissue extracellular matrix. In pharma industry, there is an urgent need for adequate 3D liver tissue models that could be used in high throughput setting for drug screening and to assess drug induced liver injury. We used SBS mats as culturing substrates for human hepatocytes to create an array of 3D human liver tissue equivalents in 96-well format. The SBS mats were highly cytocompatible, facilitated the induction of hepatocyte specific CYP gene expression in response to common medications, and supported the maintenance of hepatocyte differentiation and polarization status in long term cultures for more than 3 weeks. Together, our results show that SBS-generated gelatin scaffolds are a simple and efficient platform for use in vitro for drug testing applications.

Composite scaffolds of black phosphorus nanosheets and gelatin with controlled pore structures for photothermal cancer therapy and adipose tissue engineering

Breast cancer treatment needs to eradicate cancer cells and restore breast defects after surgical intervention. Herein, bifunctional composite scaffolds of black phosphorus nanosheets (BPNSs) and gelatin were designed to kill breast cancer cells and induce adipose tissue reconstruction. The composite scaffolds were prepared by hybridizing photothermal BPNSs with porous gelatin matrices by adding pre-prepared ice particles to precisely adjust their pore structures. The composite scaffolds had large, well-interconnected spherical pores, which allowed cell migration and infiltration. Hybridization with BPNSs increased the compression strength of the scaffolds. The composite scaffolds possessed a high photothermal conversion capacity that was dependent on the amount of BPNSs. The composite scaffold with a high amount of BPNSs could completely kill breast cancer cells in vitro and in vivo under laser irradiation. Moreover, cell culture and animal experiment results showed that the composite scaffolds promoted lipid oil droplet formation and upregulated the expression of adipogenesis-related genes when hMSCs were cultured in the scaffolds. The composite scaffolds could offer a facile platform to exert anticancer effects against breast cancer cells and promote the reconstruction of adipose tissue.

Development of genipin crosslinked gelatin matrices on surface interaction: Enhancing the biocompatibility by attenuating sterile inflammation

The inflammation can be stimulated by the surgical implantation and biomaterial presence through the foreign body via bio-interface. Macrophages play a key role in the interaction of host tissue to implant surfaces. In present study, the immuno-inflammatory responses of genipin crosslinked gelatin matrices (GCGM) to macrophages in vitro and the host tissue surfaces in rats were investigated. The results showed that the mechanical properties, swelling and degradation of gelatin matrices were improved by the crosslinking of genipin at physiological conditions. The macrophage on the surface of GCGM could avoid to be activated. The interaction of macrophage and GCGM suggested that GCGM could reduce the inflammatory response with downregulating the production and mRNA expression of pro-inflammatory cytokines. The anti-inflammatory effect of GCGM was demonstrated to be related to inhibit nuclear factor kappa-B (NF-κB) signaling pathway . Furthermore, gelatin matrices crosslinked with genipin could decrease the acute and chronic inflammatory response interacting with host tissue surfaces to enhance the biocompatibility in rats. These results showed that GCGM could avoid to active macrophages and were endowed with anti-inflammatory properties, suggesting the significant potential for clinical success with the development of immunomodulatory biomaterials.

Microwave-assisted Preparation of Cross-linked Gelatin-Paracetamol Matrices: Optimization Using the D-optimal Design

This study was conducted to assess the effect of microwave heating on the preparation of paracetamol cross-linked gelatin matrices by using the design of experiment (DoE) approach and explore the influence of the duration of microwave irradiation, the concentrations of crosslinker, and the amount of sodium bicarbonate (salt) on paracetamol release. These parameters were also compared with those of the matrices prepared via conventional heating. Twenty gel matrices were prepared with different durations of microwave irradiation, amounts of maize, and concentrations of sodium bicarbonate as suggested by Design Expert (DX®). The percentage drug release, the coefficient of variance (CV) in release, and the mean dissolution time (MDT) were the properties explored in the designed experimentation. Target responses were dependent on microwave irradiation time, cross-linker amount, and salt concentration. Classical and microwave heating did not demonstrate statistically significant difference in modifying the percentage of drug released from the matrices. However, the CVs of microwave-assisted formulations were lower than those of the gel matrices prepared via classical heating. Thus, microwave heating produced lesser variations in drug release. The optimized gel matrices demonstrated that the observed percentage of drug release, CV, and MDT were within the prediction interval generated by DX®. The release mechanism of the matrix formulations followed the Peppas-Korsmeyer anomalous transport model. The DoE-supported microwave-assisted approach could be applied to optimize the critical factors of drug release with less variation.

Raman spectroscopy assisted biochemical evaluation of L929 fibroblast cells on differentially crosslinked gelatin hydrogels

Biochemical evaluation of cell-matrix interaction using conventional labelling techniques often possesses limitations due to dye entrapment. In contrast, Raman spectroscopy guided approach offers label-free determination of cell-matrix biochemistry. Herein, gelatin (Gel) matrices modified with 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/ N-Hydroxysuccinimide (EDC/NHS) and glutaraldehyde (GTA) was used as standards for comparative evaluation. Raman spectroscopy was deployed as a label-free approach to investigate interaction of cells with Gel hydrogels. Raman-based approach assisted in evaluation of cell-matrix interactions by identifying key biomolecular signatures retrospecting the fact that L929 fibroblast cells portrayed excellent growth and proliferation kinetics in crosslinked Gel as compared to its bare counterpart. EDC crosslinked hydrogels exhibited superior cell proliferation than its GTA counterparts. Cell proliferation on differentially crosslinked gel was also confirmed using standard MTT Assay and Rhodamine-DAPI staining thus corroborating the fact that Raman spectroscopy can be deployed as a superior label-free alternative towards real-time determination of cell proliferation and growth.

Nanofibrous Gelatin-Based Biomaterial with Improved Biomimicry Using D-Periodic Self-Assembled Atelocollagen.

Design of bioinspired materials that mimic the extracellular matrix (ECM) at the nanoscale is a challenge in tissue engineering. While nanofibrillar gelatin materials mimic chemical composition and nano-architecture of natural ECM collagen components, it lacks the characteristic D-staggered array (D-periodicity) of 67 nm, which is an important cue in terms of cell recognition and adhesion properties. In this study, a nanofibrous gelatin matrix with improved biomimicry is achieved using a formulation including a minimal content of D-periodic self-assembled atelocollagen. We suggest a processing route approach consisting of the thermally induced phase separation of the gelatin based biopolymeric mixture precursor followed by chemical-free material cross-linking. The matrix nanostructure is characterized using field emission gun scanning electron microscopy (FEG-SEM), transmission electron microscopy (TEM), wide angle X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR). The cell culture assays indicate that incorporation of 2.6 wt.% content of D-periodic atelocollagen to the gelatin material, produces a significant increase of MC3T3-E1 mouse preosteoblast cells attachment and human mesenchymal stem cells (hMSCs) proliferation, in comparison with related bare gelatin matrices. The presented results demonstrate the achievement of an efficient route to produce a cost-effective, compositionally defined and low immunogenic “collagen-like” instructive biomaterial, based on gelatin.

Evaluation of smart gelatin matrices for the development of scaffolds via 3D bioprinting

Throughout history, different techniques have been used for the development of scaffolds for Tissue Engineering. Among them, three-dimensional (3D) printing for this application has been recently enhanced due to its ease in defining the structure of the material. In this sense, a novel potential alternative could be the development of a three-part device whose leading utility is to improve the introduction of the scaffold in a bioreactor. Thus, the device consists of a polycaprolactone support on which smart gelatin (GE) matrix, and finally, on top, a collagen (C) scaffold. This gelatin matrix is included to integrate the scaffold into the support, but once both are assembled, it must be removed, leaving only the support and the scaffold. Thus, in the present work, a small gelatin matrix has been evaluated. To this end, matrices with different gelatin percentages were studied, evaluating their mechanical and morphological properties at different temperatures (22 and 37 °C) to control their deposition and elimination. The results show the high application of this smart matrix for the development of scaffolds via 3D bioprinting for Tissue Engineering.

A Review of Bioactive Glass/Natural Polymer Composites: State of the Art.

Collagen, gelatin, silk fibroin, hyaluronic acid, chitosan, alginate, and cellulose are biocompatible and non-cytotoxic, being attractive natural polymers for medical devices for both soft and hard tissues. However, such natural polymers have low bioactivity and poor mechanical properties, which limit their applications. To tackle these drawbacks, collagen, gelatin, silk fibroin, hyaluronic acid, chitosan, alginate, and cellulose can be combined with bioactive glass (BG) nanoparticles and microparticles to produce composites. The incorporation of BGs improves the mechanical properties of the final system as well as its bioactivity and regenerative potential. Indeed, several studies have demonstrated that polymer/BG composites may improve angiogenesis, neo-vascularization, cells adhesion, and proliferation. This review presents the state of the art and future perspectives of collagen, gelatin, silk fibroin, hyaluronic acid, chitosan, alginate, and cellulose matrices combined with BG particles to develop composites such as scaffolds, injectable fillers, membranes, hydrogels, and coatings. Emphasis is devoted to the biological potentialities of these hybrid systems, which look rather promising toward a wide spectrum of applications.

Comparing cefotaxime and ceftriaxone in combating meningitis through nose-to-brain delivery using bio/chemoinformatics tools

Bio/chemoinformatics tools can be deployed to compare antimicrobial agents aiming to select an efficient nose-to-brain formulation targeting the meningitis disease by utilizing the differences in the main structural, topological and electronic descriptors of the drugs. Cefotaxime and ceftriaxone were compared at the formulation level (by comparing the loading in gelatin and tripalmitin matrices as bases for the formation of nanoparticulate systems), at the biopharmaceutical level (through the interaction with mucin and the P-gp efflux pumps) and at the therapeutic level (through studying the interaction with S. pneumoniae bacterial receptors). GROMACS v4.6.5 software package was used to carry-out all-atom molecular dynamics simulations. Higher affinity of ceftriaxone was observed compared to cefotaxime on the investigated biopharmaceutical and therapeutic macromolecules. Both drugs showed successful docking on mucin, P-gp efflux pump and S. pneumoniae PBP1a and 2b; but ceftriaxone showed higher affinity to the P-gp efflux pump proteins and higher docking on mucin. Ceftriaxone showed less out-of-matrix diffusion and higher entrapment on the gelatin and the tripalmitin matrices. Accordingly, Ceftriaxone gelatin nanospheres or tripalmitin solid lipid nanoparticles may pose a more feasible and efficient nose-to-brain formulation targeting the meningitis disease compared to the cefotaxime counterparts.