Poloxamer 407-Based Thermosensitive Emulgel as a Novel Formulation Providing a Controlled Release of Oil-Soluble Pharmaceuticals—Ibuprofen Case Study

This article covers the design and evaluation of a novel drug vehicle: a thermosensitive, injectable, high-oil-content (50% w/w) emulgel providing a controlled release of lipophilic pharmaceuticals. Different vegetable (castor, canola, olive, peanut, grapeseed, linseed), mineral (paraffin) and semisynthetic (isopropyl myristate, oleic acid) oils were screened for ibuprofen (IBU) solubility and for their capacity for high-shear emulsification in a 17% (w/w) aqueous solution of poloxamer 407. Chosen emulgels were subject to a rheological evaluation, a syringeability test (TA.XT texture analyser; 2 mL syringe; 18 G, 20 G and 22 G needles) and a drug release study (48 h; cellulose membrane; 0.05 mol/L phosphate buffer at pH 7.4). Castor oil turned out to be an optimal component for IBU incorporation. Blank and drug-loaded castor oil emulgels were susceptible to administration via a syringe and needle, with the absolute injection force not exceeding 3 kg (29.4 N). The drug release test revealed dose-dependent, quasi-linear kinetics, with up to 44 h of controlled, steady, linear release. The results indicate the significant potential of high-oil-content, oil-in-water thermosensitive emulgel formulations as vehicles for the controlled release of lipophilic APIs.

Investigation of an injectable gold nanoparticle extracellular matrix

Post-traumatic osteoarthritis (PTOA) is a progressive articular degenerative disease that degrades articular cartilage and stimulates apoptosis in chondrocyte cells. An injectable decellularized, extracellular matrix (ECM) scaffold, that might be able to combat the effects of PTOA, was developed where the ECM was conjugated with 20 nm gold nanoparticles (AuNP) and supplemented with curcumin and hyaluronic acid (HA). Porcine diaphragm ECM was decellularized and homogenized; AuNPs were conjugated using chemical crosslinking followed by mixing with curcumin and/or HA. Injection force testing and scanning electron microscopy with energy-dispersive X-ray spectroscopy were utilized to characterize the ECM scaffolds. In vitro testing with L929 murine fibroblasts, equine synovial fibroblasts, and Human Chondrocytes were used to determine biocompatibility, reactive oxygen species (ROS) reduction, and chondroprotective ability. The results demonstrated that conjugation of 20 nm AuNPs to the ECM was successful without significantly altering the physical properties as noted in the low injection force. In vitro work provided evidence of biocompatibility with a propensity to reduce intracellular ROS and an ability to mitigate apoptosis of chondrocyte cells stimulated with IL-1β, a known apoptosis inducing cytokine. It was concluded that an injectable AuNP-ECM may have the ability to mitigate inflammation and apoptosis.

A microfluidic approach to studying the injection flow of concentrated albumin solutions

Subcutaneous injection by means of prefilled syringes allows patients to self-administrate high-concentration (100 g/L or more) protein-based drugs. Although the shear flow of concentrated globulins or monoclonal antibodies has been intensively studied and related to the injection force proper of SC processes, very small attention has been paid to the extensional behavior of this category of complex fluids. This work focuses on the flow of concentrated bovine serum albumin (BSA) solutions through a microfluidic “syringe-on-chip” contraction device which shares some similarities with the geometry of syringes used in SC self-injection. By comparing the velocity and pressure measurements in complex flow with rheometric shear measurements obtained by means of the “Rheo-chip” device, it is shown that the extensional viscosity plays an important role in the injection process of protinaceous drugs. Article Highlights A microfluidic “syringe on chip” device mimicking the injection flow of protinaceous drugs has been developed. The velocity field of concentrated BSA solutions through the “syringe on chip” is Newtonian-like. The extensional viscosity of concentrated protein solutions should also be considered when computing injection forces through needles.

Bioactive Hydrogels: Design and Characterization of Cellulose-Derived Injectable Composites

Cellulose represents a low cost, abundant, and renewable polysaccharide with great versatility; it has a hierarchical structure composed of nanofibers with high aspect ratio (3–4 nm wide, hundreds of μm long). TEMPO-mediated oxidation represents one of the most diffused methods to obtain cellulose nanofibers (CNFs): It is possible to obtain physically crosslinked hydrogels by means of divalent cation addition. The presence of inorganic components, such as calcium phosphates (CaP), can improve not only their mechanical properties but also the bioactivity of the gels. The aim of this work is to design and characterize a TEMPO-oxidized cellulose nanofibers (TOCNFs) injectable hydrogel embedded with inorganic particles, CaP and CaP-GO, for bone tissue regeneration. Inorganic particles act as physical crosslinkers, as proven by rheological characterization, which reported an increase in mechanical properties. The average load value registered in injection tests was in the range of 1.5–4.4 N, far below 30 N, considered a reasonable injection force upper limit. Samples were stable for up to 28 days and both CaP and CaP-GO accelerate mineralization as suggested by SEM and XRD analysis. No cytotoxic effects were shown on SAOS-2 cells cultured with eluates. This work demonstrated that the physicochemical properties of TOCNFs-based dispersions could be enhanced and modulated through the addition of the inorganic phases, maintaining the injectability and bioactivity of the hydrogels.

Silanization of Chitosan and Hydrogel Preparation for Skeletal Tissue Engineering

Tissue engineering is a multidisciplinary field that relies on the development of customized biomaterial to support cell growth, differentiation and matrix production. Toward that goal, we designed the grafting of silane groups onto the chitosan backbone (Si-chito) for the preparation of in situ setting hydrogels in association with silanized hydroxypropyl methylcellulose (Si-HPMC). Once functionalized, the chitosan was characterized, and the presence of silane groups and its ability to gel were demonstrated by rheology that strongly suggests the presence of silane groups. Throughout physicochemical investigations, the Si-HPMC hydrogels containing Si-chito were found to be stiffer with an injection force unmodified. The presence of chitosan within the hydrogel has demonstrated a higher adhesion of the hydrogel onto the surface of tissues. The results of cell viability assays indicated that there was no cytotoxicity of Si-chito hydrogels in 2D and 3D culture of human SW1353 cells and human adipose stromal cells, respectively. Moreover, Si-chito allows the transplantation of human nasal chondrocytes in the subcutis of nude mice while maintaining their viability and extracellular matrix secretory activity. To conclude, Si-chito mixed with Si-HPMC is an injectable, self-setting and cytocompatible hydrogel able to support the in vitro and in vivo viability and activity of hASC.

Injectability of Thermosensitive, Low-Concentrated Chitosan Colloids as Flow Phenomenon through the Capillary under High Shear Rate Conditions

Low-concentrated colloidal chitosan systems undergoing a thermally induced sol–gel phase transition are willingly studied due to their potential use as minimally invasive injectable scaffolds. Nevertheless, instrumental injectability tests to determine their clinical utility are rarely performed. The aim of this work was to analyze the flow phenomenon of thermosensitive chitosan systems with the addition of disodium β-glycerophosphate through hypodermic needles. Injectability tests were performed using a texture analyzer and hypodermic needles in the sizes 14G–25G. The rheological properties were determined by the flow curve, three-interval thixotropy test (3ITT), and Cox–Merz rule. It was found that reducing the needle diameter and increasing its length and the crosshead speed increased the injection forces. It was claimed that under the considered flow conditions, there was no need to take into account the viscoelastic properties of the medium, and the model used to predict the injection force, based solely on the shear-thinning nature of the experimental material, showed very good agreement with the experimental data in the shear rate range of 200–55,000 s−1. It was observed that the increase in the shear rate value led to macroscopic structural changes of the chitosan sol caused by the disentangling and ordering of the polysaccharide chains along the shear field.

Evaluation of Eleview® Bioadhesive Properties and Cushion-Forming Ability

Submucosal injection is generally required for both endoscopic-mucosal resection (EMR) and submucosal dissection (ESD). SIC-8000 (Eleview®) is a new liquid composition in the form of a microemulsion for submucosal injection, approved by the Food and Drug Administration (FDA) 510(k) and Conformité Européene (CE) marked, containing a biocompatible polymer as a cushioning agent. The aim of this study was to evaluate Eleview®’s performance in terms of bioadhesive properties and cushion-forming ability. The bioadhesion was evaluated by measuring the interaction between Eleview® and the extracellular matrix (the main component of the submucosal layer) using the texture analyzer. To better comprehend the mechanism of action of Eleview® after submucosal injection, force of detachment and adhesion work were measured for the following formulations: Eleview®, Eleview® without poloxamer (functional polymer), poloxamer solution alone, normal saline, and MucoUp® (competing product on the Japanese market). The results obtained show the interaction between Eleview® and the extracellular matrix, highlighting the stronger bioadhesive properties of Eleview® compared with Eleview® without poloxamer, poloxamer solution alone, as well as normal saline and MucoUp®. The ability of Eleview® to form a consistent and long-lasting cushion in situ, once injected into the submucosal layer, was tested ex vivo on a porcine stomach. The results obtained show a better permanence in situ for the product compared with normal saline injection and to MucoUp® (t-test, p < 0.05).