Incorporation Of Dexamethasone Research Articles

O-carboxymethylchitosan hydrogel loaded with dexamethasone for intraocular use

This study aimed to develop hydrogels from carboxymethyl chitosan (CMC), and carboxymethyl chitosan (CMC) with dexamethasone (DEX) for intraocular application, aiming to provide structural stability to the eye and attenuation of inflammatory processes. CMC hydrogels were prepared at concentrations of 0.5%, 1% and 2% (w/v) and incorporated with 10% (v/v) DEX. The samples were characterized by FT-IR spectroscopic, thermogravimetric analysis, injectability, rheology, and cytotoxicity. The results showed that the incorporation of DEX did not significantly alter the absorption bands and thermal behavior of the CMQ hydrogels. Injectability tests revealed that hydrogels with DEX require injection force similar to the commercial material. In rheological tests, pseudoplastic and linear viscoelastic behavior was identified. Cytotoxicity tests confirmed the biocompatibility of the hydrogels. These results demonstrate that the developed hydrogels have properties suitable for biomedical applications, especially aimed at the ophthalmological context.

ROS-Scavenging Lignin-Based Tolerogenic Nanoparticle Vaccine for Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating autoimmune disease, in which the immune system attacks myelin. Although systemic immunosuppressive agents have been used to treat MS, long-term treatment with these drugs causes undesirable side effects such as altered glucose metabolism, insomnia, and hypertension. Herein, we propose a tolerogenic therapeutic vaccine to treat MS based on lignin nanoparticles (LNP) with intrinsic reactive oxygen species (ROS)-scavenging capacity derived from their phenolic moieties. The LNP loaded with autoantigens of MS allowed for inducing tolerogenic DCs with low-level expression of costimulatory molecules while presenting antigenic peptides. Intravenous injection of an LNP-based tolerogenic vaccine into an experimental autoimmune encephalomyelitis (EAE) model led to durable antigen-specific immune tolerance via inducing regulatory T cells (Tregs). Autoreactive T helper type 1 cells, T helper type 17 cells, and inflammatory antigen presentation cells (APCs) were suppressed in the central nervous system (CNS), ameliorating ongoing MS in early and late disease states. Additionally, the incorporation of dexamethasone into an LNP-based tolerogenic nanovaccine could further improve the recovery of EAE mice in the severe chronic stage. As lignin is the most abundant biomass and waste byproduct in the pulping industry, a lignin-based tolerogenic vaccine could be a novel, cost-effective, high-value vaccine platform with potent therapeutic efficiency in treating autoimmune diseases.

Structurally dynamic self-healable hydrogel cooperatively inhibits intestinal inflammation and promotes mucosal repair for enhanced ulcerative colitis treatment

Hydrogels are a class of biocompatible materials with versatile functions that have been increasing explored for the localized treatment of ulcerative colitis (UC), but various mechanical stimuli may cause premature hydrogel breakage and detachment, impeding their further clinical translation. Here we report a multifunctional mechanically-resilient self-healing hydrogel for effective UC treatment, which is synthesized through the host-guest interaction between dopamine/β-cyclodextrin-modified hyaluronic acid (HA-CD-DA) and amantadine-modified carboxymethyl chitosan (CMCS-AD). The excessive β-CD cavities allow the incorporation of dexamethasone (DEX), while the porous hydrogel network potentiates the encapsulation of basic fibroblast growth factor (bFGF) and L-alanyl-l-glutamine (ALG). DA moieties in HA components allow firm adhesion of the hydrogel to the ulcerative lesions after in-situ implantation, while the reversible host-guest interaction between CD and AD could enhance the persistence of hydrogel. The hydrogel demonstrated favorable biocompatibility and could continuously release DEX to induce M1-to-M2 repolarization of mucosal macrophages through inhibiting the toll-like receptor 4 (TLR4)-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) axis. Furthermore, the co-delivered bFGF and ALG facilitates the regeneration of ulcerative mucosa and restore its barrier functions to ameliorate UC symptoms. The mechanically resilient hydrogel offers an integrative approach for UC therapy in the clinics.

Dexamethasone release from photopolymerised PEGDA700 for cochlea drug delivery

Abstract Sustained local drug release and high local drug concentrations can be achieved by specially designed DDSs, which can be created for different applications. This results in therapeutic drug amounts at the site of action, simultaneously providing a very low drug amount in total. Bodily compartments that contain liquids may be used to transport the drugs from DDS into the tissue, such as the cochlea with the perilymph in the case of cochlea implants. However, predominantly dry environments, such as the middle ear, are lacking such a medium but may deliver enough moisture for the use of swellable DDS through the surrounding mucus membranes. Therefore, DDS with new functionalities are needed to ensure a sustained drug release. In this study, the release of dexamethasone out of a photopolymer system is presented. The system is built from UV-polymerized PEGDA followed by the incorporation of dexamethasone via swelling. The drug release is tested in vitro with isotonic NaCl solution for specified time periods, showing two phases: a swelling phase and a release phase. After the swelling phase the concentration of dexamethasone in the release medium was not controlled by diffusion, although sink conditions were ensured. In contrast, this system can be used to release the drug until equilibrium with a final medium concentration that is far below the solubility of dexamethasone. Hence, such DDS may be useful for dexamethasone delivery into the cochlea through the round window membrane by ensuring a constant concentration in the perilymph.

Preparation of dexamethasone-loaded calcium phosphate nanoparticles for the osteogenic differentiation of human mesenchymal stem cells.

As an earliest known and readily available osteogenic inducer for stem cells, dexamethasone (DEX) plays a key role in affecting cell functions and cellular processes, especially for cell proliferation and differentiation. However, the clinical application of DEX has been limited because of its uncontrolled release. An ideal carrier is desired to control the DEX release for the osteogenic differentiation of stem cells and bone tissue engineering. Biphasic calcium phosphate nanoparticles (BCP-NPs) should be potential carriers for DEX due to their osteoconductive properties and good biocompatibility as a bone graft biomaterial. In this study, DEX-loaded BCP-NPs were prepared by two methods: (1) immersion of BCP-NPs in a DEX solution (denoted DEX/BCP-NPs), (2) DEX incorporation during BCP-NP formation in a calcifying solution (denoted DEX@BCP-NPs). The DEX@BCP-NPs showed a higher DEX loading amount and more sustainable DEX release than did the DEX/BCP-NPs. The DEX@BCP-NPs were used for the culture of human bone marrow-derived mesenchymal stem cells (hMSCs) and showed a promotive effect on the proliferation of hMSCs. Furthermore, the DEX@BCP-NPs significantly increased the alkaline phosphatase (ALP) activity, calcium deposition and gene expressions of the osteogenic markers of hMSCs when compared to BCP-NPs without DEX loading. The results demonstrated BCP-NPs were good carriers for DEX loading and the DEX@BCP-NPs should be useful for bone tissue engineering.

Magnetic hyaluronic acid nanospheres via aqueous Diels–Alder chemistry to deliver dexamethasone for adipose tissue engineering

Biopolymer-based nanospheres have great potential in the field of drug delivery and tissue regenerative medicine. In this work, we present a flexible way to conjugate a magnetic hyaluronic acid (HA) nanosphere system that are capable of vectoring delivery of adipogenic factor, e.g. dexamethasone, for adipose tissue engineering. Conjugation of nanospheres was established by aqueous Diels–Alder chemistry between furan and maleimide of HA derivatives. Simultaneously, a furan functionalized dexamethasone peptide, GQPGK, was synthesized and covalently immobilized into the nanospheres. The magnetic HA nanospheres were fabricated by encapsulating super-paramagnetic iron oxide nanoparticles, which exhibited quick magnetic sensitivity. The aqueous Diels–Alder chemistry made nanospheres high binding efficiency of dexamethasone, and the vectoring delivery of dexamethasone could be easily controlled by a external magnetic field. The potential application of the magnetic HA nanospheres on vectoring delivery of adipogenic factor was confirmed by co-culture of human adipose-derived stem cells (ASCs). In vitro cytotoxicity tests demonstrated that incorporation of dexamethasone into magnetic HA nanospheres showed high efficiency to promote ASCs viabilities, in particular under a magnetic field, which suggested a promising future for adipose regeneration applications.

Effect of embedded dexamethasone in cochlear implant array on insertion forces in an artificial model of scala tympani.

Loading otoprotective drug into cochlear implant might change its mechanical properties, thus compromising atraumatic insertion. This study evaluated the effect of incorporation of dexamethasone (DXM) in the silicone of cochlear implant arrays on insertion forces. Local administration of DXM with embedded array can potentially reduce inflammation and fibrosis after cochlear implantation procedure to improve hearing preservation and reduce long-term impedances. Four models of arrays have been tested: 0.5-mm distal diameter array (n = 5) used as a control, drug-free 0.4-mm distal diameter array (n = 5), 0.4-mm distal diameter array with 1% eluded DXM silicone (n = 5), and 0.4-mm distal diameter array with 10% eluded DXM silicone (n = 5). Via a motorized insertion bench, each array has been inserted into an artificial scala tympani model. The forces were recorded by a 6-axis force sensor. Each array was tested seven times for a total number of 140 insertions. During the first 10-mm insertion, no difference between the four models was observed. From 10- to 24-mm insertion, the 0.5-mm distal diameter array presented higher insertion forces than the drug-free 0.4-mm distal diameter arrays, with or without DXM. Friction forces for drug-free 0.4-mm distal diameter array and 0.4-mm distal diameter DXM eluded arrays were similar on all insertion lengths. Incorporation of DXM in silicone for cochlear implant design does not change electrode array insertion forces. It does not raise the risk of trauma during array insertion, making it suitable for long-term in situ administration to the cochlea.

Design and functionalization of chitin-based microsphere scaffolds

Chitin agglomerated scaffolds were produced and functionalized using green chemistry principles and clean technologies. This combination enabled the functionalization of chitin microparticles prepared by dissolution of the polymer in ionic liquids, followed by the application of a sol–gel method. Finally, the 3D constructs were moulded and dried by a supercritical assisted agglomeration method. Structural and morphological characterization was performed using scanning electron microscopy (SEM) and micro-computed tomography (μ-CT). An evaluation of the bioactive behavior of the matrices was done by immersing them in simulated body fluid (SBF) for up to 21 days. The potential use of such matrices as drug delivery systems was evaluated after the incorporation of dexamethasone into the matrices during drying in supercritical assisted agglomeration. The findings suggested that the morphological features such as porosity, interconnectivity and pore size distribution of the matrices can be tuned by changing the particle size, chitin concentration and the pressure applied during moulding. Chitin microspheres were modified by siloxane and silanol groups, providing a bioactive behavior; the apatite formation was shown to be dependent on the amount and arrangement of silanol groups. Furthermore, in vitro drug release studies showed that dexamethasone was sustainably released. All these findings suggest that this strategy is a feasible and advantageous process to obtain chitin-based 3D structures with both functional and structural characteristics that make them suitable for regenerative medicine applications.

Development of a specially tailored local drug delivery system for the prevention of fibrosis after insertion of cochlear implants into the inner ear

A cochlear implant (CI)-associated local drug delivery system based on dexamethasone (DMS) was developed with the purpose to inhibit the growth of fibrotic tissue which influences the signal transmission from the CI to the neurons of the inner ear. For the realization of a targeted DMS delivery the following concepts were combined: modification of the silicone-based electrode carrier by incorporation of DMS and a DMS-containing polymeric coating chemically attached on the surface of the electrode carrier. It was demonstrated that the coated CI showed a high coating stability in a simulated implantation procedure. The in vitro drug release studies in a quasi-stationary model revealed a faster DMS release in the initial phase originating from the DMS-containing coatings and then a lower and sustained DMS release originating from the DMS-loaded silicone carrier. The performed in vitro biocompatibility study confirmed that the released DMS was non-toxic for cultured spiral ganglion cells.

Physicochemical properties of extruded and non-extruded liposomes containing the hydrophobic drug dexamethasone

The physicochemical and release properties of non-extruded ‘multilamellar’ and small sonicated and extruded 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) liposomes containing hydrophobic drug dexamethasone were investigated. Non-extruded liposomes had similar diameter, however dexamethasone encapsulation decreased with increase in lipid chain length. Dexamethasone destabilized the liposome membranes as indicated by decrease in enthalpy and increase in the peak width of the main transition. Based on calorimetric analysis, it appeared that dexamethasone and cholesterol were heterogeneously distributed in the non-extruded liposomes. Sonication and extrusion reduced the diameter (DSPC > DPPC > DMPC) and decreased drug encapsulation (approximately 50%). Cholesterol incorporation decreased drug encapsulation in both extruded and non-extruded DMPC liposomes which appeared to be due to structural similarities between cholesterol and dexamethasone. Incorporation of dexamethasone and cholesterol in the same DMPC liposomes caused a marked perturbation in the phase transition. Dexamethasone release from extruded liposomes was fast, while non-extruded liposomes showed slower release. Release was fastest from DMPC liposomes and slowest from liposomes of high phase transition lipid DSPC. Incorporation of cholesterol did not decrease release from DMPC liposomes. These results indicated that change in the physicochemical properties and the phase transition behavior of liposomes, due to processing as well as incorporation of hydrophobic drug dexamethasone, changed their release properties.

Dexamethasone Incorporating Liposomes: Effect of Lipid Composition on Drug Trapping Efficiency and Vesicle Stability

Effect of lipid composition on encapsulation and stability of dexamethasone (DXM) incorporating multilamellar vesicles (MLV) is studied. MLVs composed of phosphatidylcholine (PC) or distearoyl-glycero-PC (DSPC), with or without cholesterol (Chol), are prepared and the release of DXM during vesicle incubation in buffer or plasma proteins is evaluated. Incorporation of DXM is slightly higher in DSPC liposomes compared with PC, whereas the drug is displaced from liposomes, as the Chol content of liposome membranes increases. Plain lipid and Chol-containing liposomes lose similar fractions of vesicle-incorporated DXM during incubation in buffer or serum, whereas DXM release kinetics are similar (for each liposome type studied), implying that drug release is due mainly to dilution of liposome dispersions that leads to repartitioning of DXM.

Prolonged Regional Anesthesia with Lidocaine Microspheres by Using a Biodegradable Polymer

Background : Biodegradable microspheres are a useful method of drug delivery because they are both injectable and biodegradable. Previous work in our group has characterized implantable preparations of local anesthetics in pellets for prolonged regional anesthesia. In this paper we evaluated injectable suspensions of lidocaine-polymer microspheres for extended period of percutaneous sciatic nerve blockade in rats. Methods : Microspheres were prepared using poly (lactide-co-glycolide) loaded with 50 wt% lidocaine by a solvent evaporation method. In vitro release rate of lidocaine from microspheres was determined by high performance liquid chromatography (HPLC). Percutaneous blockade of the rat sciatic nerve was performed, and sensory blockade of the nerve was assessed using an analgesiometer. Results : Lidocaine was released in a controlled manner in vitro. In general 60% of the drug released in the first day, 80% in two days. Sciatic nerve blockade duration ranged from 8 to 12 hours. Incorporation of dexamethasone 0.05 wt% into the microspheres resulted in significant prolongation of block. Conclusion : Prolonged percutaneous blockade of peripheral nerve is achieved using biodegradable polymeric lidocaine microspheres. (Korean J Anesthesiol 1999; 36: 305∼310)

Glucocorticoids prolong rat sciatic nerve blockade in vivo from bupivacaine microspheres.

Previous work showed that incorporation of dexamethasone (0.05 weight/weight percentage) into bupivacaine microspheres prolonged blockade by eight to 13 times compared with that produced by bupivacaine microspheres alone. The determinants of dexamethasone's block-prolonging effect were examined and reported here. Polylactic-co-glycolic acid polymer microspheres (65/35) with 75 weight/weight percentage bupivacaine were prepared. Microspheres were injected adjacent to the rat sciatic nerve, and sensory and motor blockade were assessed. A procedure was developed to test drugs for block-prolonging ability in vivo by placing test drugs in the injection fluid along with a suspension of bupivacaine microspheres. Dexamethasone alone in suspension did not produce blockade, nor did it prolong blockade induced by aqueous bupivacaine. Bupivacaine microspheres (150 mg drug/kg rat weight) produced blockade for 6 to 10 h. Dexamethasone in the suspending solution of microspheres prolonged block by up to five times. Glucocorticoids prolonged block in proportion to glucocorticoid/antiinflammatory potency. The corticosteroid antagonist cortexolone inhibited dexamethasone's blockade-prolonging action. Durations of blockade with or without dexamethasone were unaltered by hydroxyurea-induced neutrophil depletion. Microspheres were extracted from rats at time points ranging from 7 h to 7 days, and residual microsphere dry weight and bupivacaine content were similar in groups of rats injected with either bupivacaine microspheres or bupivacaine microspheres containing dexamethasone, respectively. Glucocorticoids prolong blockade from bupivacaine microspheres. The mechanism appears unrelated to the kinetics of bupivacaine release in vivo.

Micro high-performance liquid chromatographic determination of cardiac glycosides in β-methyldigoxin and digoxin tablets

A micro high-performance liquid chromatographic (micro-HPLC) method has been developed for the assay of β-methyldigoxin and digoxin tablets. Quantitation of cardiac glycosides in tablets was carried out by the incorporation of dexamethasone as an internal standard. The procedure consisted of disintegration of tablets, extraction with acetone-ethanol (9:1) and injection for micro-HPLC on an ODS micro column, using acetonitrile-water (28:72) for β-methyldigoxin tablets and methanol-water (1:1) for digoxin tablets; the effluent was monitored by UV detection at 220 nm. The average values of the contents in β-methyldigoxin and digoxin tablets were 99.6 and 100.2% of the labelled amounts, respectively. The proposed method is sufficiently precise and sensitive to examine the content uniformity of tablets.

Growth ofCandida albicansin dexamethasone-supplemented media

Candida albicans grown in dexamethasone (DXM) shows an apparent increase in dry weight. This increase, however, represents an artefact due to entrapment and incorporation of DXM by the yeast. Thus opportunistic infections by C. albicans which are promoted by DXM must be due entirely to effects other than growth enhancement of the organism.

Incorporation of steroid hormones in nuclei of different ploidy and different phases of the cell cycle

The incorporation in dido of oestradiol in mouse mammary tumour nuclei, and of dexamethasone in nuclei of rat liver, regenerating rat liver and hepatoma was investigated. The nuclei were fractionated in various ploidy classes by sedimentation at unit gravity. Incorporation of oestradiol was about six times higher in both diploid and tetraploid nuclei of hormone responsive mammary tumours of GR mice, than in the respective nuclei of hormone independent tumours. Dexamethasone was incorporated in both diploid and polyploid nuclei of rat liver, regenerating liver and hepatoma BY484. Incorporation of dexamethasone in vivo and in vitro increased with increasing ploidy of the nuclei. The results indicate that in proliferating normal and cancer tissues, translocation of receptor-bound steroid hormones occurs during both the g 1, S and G 2 phases of the cell mitotic cycle. The amount of hormone incorporated per nucleus in vivo and in vitro depends on the ploidy of the nucleus and on the receptor concentration in the cytoplasm.

Murine mammary tumor virus (MuMTV) infection of an epithelial cell line established from C57BL/6 mouse mammary glands

An epithelioid cell line derived from the mammary glands of a C57BL/6 mouse and designated C57MG cell line was found to be susceptible to infection by routine mammary tumor virus (MuMTV). Although uninfected C57MG cells contain endogenous MuMTV-related DNA sequences, no RNA sequences homologous to MuMTV were detectable, even after treatment with the glucocorticoid, dexamethasone. However, after infection with MuMTV, these cells acquire additional MuMTV DNA, and viral RNA and proteins were readily detectable. Most, if not all, of the additional MuMTV DNA in infected C57MG cells appeared to be integrated. Synthesis of viral RNA and protein, and the release of virions into culture fluid by infected C57MG cells, was stimulated by incorporation of dexamethasone in the growth medium. The efficiency of infection by MuMTV in C57MG cells was similar to that in nonmurine cells. There was a direct relationship between multiplicity of infection (m.o.i.) and the average number of MuMTV RNA molecules detected per cell 5 weeks after infection. However, even at the highest m.o.i. used (4 × 10 5 virions/cell), a plateau in the average number of viral RNA molecules per cell was not achieved. The origin of MuMTV synthesized by infected C57MG cells, whether it is the progeny of infecting MuMTV or of the endogenous C57BL/6 MuMTV or of both, remains undetermined. We have been unable to detect any morphological or growth pattern changes in C57MG cells following infection with MuMTV.