Evaluation of hyaluronic acid nanoparticle embedded chitosan-gelatin hydrogels for antibiotic release.

The development of chitosan-gelatin (CS-G) hydrogels embedded with ampicillin-loaded hyaluronic acid nanoparticles (HA-NPs) for wound dressing is proposed. It was aimed to provide controlled ampicillin delivery by incorporation of HA-NPs into biocompatible CS-G hydrogel structure. According to in vitro ampicillin release studies, 55% of ampicillin was released from CS-G/HA-NPs hydrogels after 5 days. Antibacterial performance of CS-G/HA-NPs hydrogels was proven with agar disc diffusion test. For cytotoxicity assay, fibroblast cell viability increased in CS-G/HA-NPs hydrogels compared with CS-G group after 24 hr incubation. Consequently, the potential ability of CS-G/HA-NPs hydrogels as a controlled drug delivery system has been verified.

Application of Nanoemulsions (W/O) of Extract of Opuntia oligacantha C.F. Först and Orange Oil in Gelatine Films.

Over the past decade, consumers have demanded natural, completely biodegradable active packaging serving as food containers. Bioactive plant compounds can be added to biopolymer-based films to improve their functionality, as they not only act as barriers against oxidation, microbiological, and physical damage, they also offer functionality to the food they contain. A water-in-oil (W/O) nanoemulsion was produced by applying ultrasound to xoconostle extract and orange oil, and was incorporated into gelatine films in different proportions 1:0 (control), 1:0.10, 1:0.25, 1:0.50, 1:0.75, and 1:1 (gelatine:nanoemulsion). The nanoemulsions had an average size of 118.80 ± 5.50 nm with a Z-potential of -69.9 ± 9.93 mV. The presence of bioactive compounds such as phenols, flavonoids, and betalains in the films was evaluated. The 1:1 treatment showed the highest presence of bioactive compounds, 41.31 ± 3.71 mg of gallic acid equivalent per 100 g (GAE)/100g for phenols, 28.03 ± 3.25 mg of quercetin equivalent per 100 g (EQ)/100g flavonoids and 0.014 mg/g betalains. Radical inhibition reached 72.13% for 2,20-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and 82.23% for 1,1-diphenyl-2-picrylhydrazyl (DPPH). The color of the films was influenced by the incorporation of nanoemulsions, showing that it was significantly different (p < 0.05) to the control. Mechanical properties, such as tensile strength, Young's modulus, and percentage elongation, were affected by the incorporation of nanoemulsified bioactive compounds into gelatine films. The obtained films presented changes in strength and flexibility. These characteristics could be favorable as packaging material.

3D Bioprinting of Carbohydrazide-Modified Gelatin into Microparticle-Suspended Oxidized Alginate for the Fabrication of Complex-Shaped Tissue Constructs.

Extrusion-based bioprinting of hydrogels in a granular secondary gel enables the fabrication of cell-laden three-dimensional (3D) constructs in an anatomically accurate manner, which is challenging using conventional extrusion-based bioprinting processes. In this study, carbohydrazide-modified gelatin (Gel-CDH) was synthesized and deposited into a new multifunctional support bath consisting of gelatin microparticles suspended in an oxidized alginate (OAlg) solution. During extrusion, Gel-CDH and OAlg were rapidly cross-linked because of the Schiff base formation between aldehyde groups of OAlg and amino groups of Gel-CDH, which has not been demonstrated in the domain of 3D bioprinting before. Rheological results indicated that hydrogels with lower OAlg to Gel-CDH ratios possessed superior mechanical rigidity. Different 3D geometrically intricate constructs were successfully created upon the determination of optimal bioprinting parameters. Human mesenchymal stem cells and human umbilical vein endothelial cells were also bioprinted at physiologically relevant cell densities. The presented study has offered a novel strategy for bioprinting of natural polymer-based hydrogels into 3D complex-shaped biomimetic constructs, which eliminated the need for cytotoxic supplements as external cross-linkers or additional cross-linking processes, therefore expanding the availability of bioinks.

Intra-articular delivery of sinomenium encapsulated by chitosan microspheres and photo-crosslinked GelMA hydrogel ameliorates osteoarthritis by effectively regulating autophagy.

Reduced expression of autophagy regulators has been observed in pathological cartilage in humans and mice. The present study aimed to investigate the synergistic therapeutic effect of promotion of chondrocyte autophagy via exposure to sinomenium (SIN) encapsulated by chitosan microspheres (CM-SIN) and photo-crosslinked gelatin methacrylate (GelMA) hydrogel, with the goal of evaluating CM-SIN as a treatment for patients with osteoarthritis. First, we fabricated and characterized GelMA hydrogels and chitosan microspheres. Next, we measured the effect of SIN on cartilage matrix degradation induced by IL1-ß in chondrocytes and an ex vivo model. SIN ameliorated the pathological changes induced by IL1-ß at least partially through activation of autophagy. Moreover, we surgically induced osteoarthritis in mice, which were injected intra-articularly with CM-SIN and GelMA. Cartilage matrix degradation and chondrocyte autophagy were evaluated 4 and 8 weeks after surgery. Treatment with the combination of CM-SIN and GelMA retarded the progression of surgically induced OA. SIN ameliorated cartilage matrix degradation at least partially by inducing autophagy in vivo. Our results demonstrate that injection of the combination of GelMA hydrogel and CM-SIN could be a promising strategy for treating patients with osteoarthritis.

Evaluating gelatin based nanoparticles as a carrier system for double stranded oligonucleotides.

PURPOSE: Surface modified gelatin nanoparticles were tested as a potential carrier system for double stranded DNA and RNA oligonucleotides. The results will be discussed with regard to former experiments conducted with single stranded oligonucleotides. METHODS: Gelatin nanoparticles were prepared by a two step desolvation method and surface modified by the covalent coupling of a quaternary amine to obtain a permanent positive net charge. Oligonucleotide loading was conducted in three different media applying 50 microg oligonucleotide per mg nanoparticles in total. Five batches of nanoparticles varying in size and zeta potential (zeta) were tested. The zeta potentials were determined under enforced ionic conditions in a 10 mmol sodium chloride solution at pH 7.0. The separation of unbound oligonucleotides and gelatin nanoparticles was achieved by centrifugation. Free oligonucleotide was determined UV-spectrophotometrically (260 nm) in the supernatant. RESULTS: It could be shown that up to 50 microg nucleic acid per mg nanoparticles can be bound depending on the particle's zeta potential and the chosen incubation medium. CONCLUSIONS: The results suggest that the proposed procedure allows a successful drug loading of double stranded oligonucleotides onto to the surface of accordingly modified gelatin nanoparticles.

Preparation and evaluation of drug-loaded gelatin nanoparticles for topical ophthalmic use.

Gelatin nanoparticles encapsulating pilocarpine HCl or hydrocortisone as model drugs were produced using a desolvation method. The influence of a number of preparation parameters on the particle properties was investigated. For the pilocarpine HCl-loaded spheres, an influence of the pH during particle preparation on the size was observed. Slightly negative zeta potential values were measured for all samples. In the case of pilocarpine HCl-loaded spheres, no influence of the gelatin type or the pH level was observed, which could be attributed to the shielding effect of ions present in the dispersion medium. When hydrocortisone was entrapped, a difference in zeta potential value between gelatin type A and gelatin type B particles was measured. A high pilocarpine HCl entrapment was established. Hydrocortisone was complexed with cyclodextrins in order to increase its aqueous solubility. The drug encapsulation was lower than in the case of pilocarpine HCl, but still amounted to approximately 30-40%. Compared to the aqueous drug solutions, a sustained release for both drugs was observed. The release kinetics of pilocarpine HCl are close to zero order, and no significant differences were measured between the various preparations. In the case of hydrocortisone, the release data suggests a difference in release rate depending on the type of cyclodextrin employed.