Dexamethasone 21-phosphate disodium salt

Electrofluidic control of bioactive molecule delivery into soft tissue models based on gelatin methacryloyl hydrogels using threads and surgical sutures.[Pubmed:32345999]

Sci Rep. 2020 Apr 28;10(1):7120.

The delivery of bioactive molecules (drugs) with control over spatial distribution remains a challenge. Herein, we demonstrate for the first time an electrofluidic approach to controlled delivery into soft tissue models based on gelatin methacryloyl (GelMA) hydrogels. This was achieved using a surgical suture, whereby transport of bioactive molecules, including drugs and proteins, was controlled by imposition of an electric field. Commonly employed surgical sutures or acrylic threads were integrated through the hydrogels to facilitate the directed introduction of bioactive species. The platform consisted of two reservoirs into which the ends of the thread were immersed. The anode and cathode were placed separately into each reservoir. The thread was taken from one reservoir to the other through the gel. When current was applied, biomolecules loaded onto the thread were directed into the gel. Under the same conditions, the rate of movement of the biomolecules along GelMA was dependent on the magnitude of the current. Using 5% GelMA and a current of 100 microA, 2 uL of fluorescein travelled through the hydrogel at a constant velocity of 7.17 +/- 0.50 um/s and took less than 8 minutes to exit on the thread. Small molecules such as riboflavin migrated faster (5.99 +/- 0.40 mum/s) than larger molecules such as dextran (2.26 +/- 0.55 mum/s with 4 kDa) or BSA (0.33 +/- 0.07 mum/s with 66.5 kDa). A number of commercial surgical sutures were tested and found to accommodate the controlled movement of biomolecules. Polyester, polyglactin 910, glycolide/lactide copolymer and polyglycolic acid braided sutures created adequate fluid connection between the electrodes and the hydrogel. With a view to application in skin inflammatory diseases and wound treatment, wound healing, slow and controlled delivery of Dexamethasone 21-phosphate disodium salt (DSP), an anti-inflammatory prodrug, was achieved using medical surgicryl PGA absorbable suture. After 2 hours of electrical stimulation, still 81.1% of the drug loaded was encapsulated within the hydrogel.

Supercritical impregnation and optical characterization of loaded foldable intraocular lenses using supercritical fluids.[Pubmed:29120719]

J Cataract Refract Surg. 2017 Oct;43(10):1343-1349.

PURPOSE: To prepare drug-loaded intraocular lenses (IOLs) used to combine cataract surgery with postoperative complication treatment through supercritical impregnation while preserving their optical properties. SETTING: Aix-Marseille Universite, CNRS, Centrale Marseille, Laboratoire de Mecanique, Modelisation & Procedes Propres, Marseille, France, and He University Eye Hospital, Liaoning Province, China. DESIGN: Experimental study. METHODS: Supercritical impregnations of commercial foldable IOLs used in cataract surgery with ciprofloxacin (an antibiotic) and Dexamethasone 21-phosphate disodium salt (an antiinflammatory drug) were performed in a noncontinuous mode. Impregnation amounts were determined through drug-release kinetic studies. The optical characterizations of IOLs were determined by evaluating the dioptric power and the imaging quality by determining the modulating transfer function (MTF) at a specified spatial frequency according to the International Organization for Standardization (ISO 11979-2:2014). RESULTS: Transparent IOLs presenting an effective impregnation were obtained with a prolonged drug delivery during approximately 10days. Optical characterizations (dioptric powers and MTF values) show preserved optical properties after supercritical treatment/impregnation. CONCLUSION: Supercritical treatments/impregnations do not damage the optical properties of IOLs and are therefore adequate for the preparation of delivery devices used for cataract surgery.

Preparation of Biodegradable and Elastic Poly(epsilon-caprolactone-co-lactide) Copolymers and Evaluation as a Localized and Sustained Drug Delivery Carrier.[Pubmed:28335550]

Int J Mol Sci. 2017 Mar 21;18(3). pii: ijms18030671.

To develop a biodegradable polymer possessing elasticity and flexibility, we synthesized MPEG-b-(PCL-co-PLA) copolymers (PCxLyA), which display specific rates of flexibility and elasticity. We synthesize the PCxLyA copolymers by ring-opening polymerization of epsilon-caprolactone and l-lactide. PCxLyA copolymers of various compositions were synthesized with 500,000 molecular weight. The PCxLyA copolymers mechanical properties were dependent on the mole ratio of the epsilon-caprolactone and l-lactide components. Cyclic tensile tests were carried out to investigate the resistance to creep of PCxLyA specimens after up to 20 deformation cycles to 50% elongation. After in vivo implantation, the PCxLyA implants exhibited biocompatibility, and gradually biodegraded over an eight-week experimental period. Immunohistochemical characterization showed that the PCxLyA implants provoked in vivo inflammation, which gradually decreased over time. The copolymer was used as a drug carrier for locally implantable drugs, the hydrophobic drug dexamethasone (Dex), and the water-soluble drug Dexamethasone 21-phosphate disodium salt (Dex(p)). We monitored drug-loaded PCxLyA films for in vitro and in vivo drug release over 40 days and observed real-time sustained release of near-infrared (NIR) fluorescence over an extended period from hydrophobic IR-780- and hydrophilic IR-783-loaded PCxLyA implanted in live animals. Finally, we confirmed that PCxLyA films are usable as biodegradable, elastic drug carriers.

Formulation, functional evaluation and ex vivo performance of thermoresponsive soluble gels - A platform for therapeutic delivery to mucosal sinus tissue.[Pubmed:27771516]

Eur J Pharm Sci. 2017 Jan 1;96:499-507.

Mucoadhesive in situ gelling systems (soluble gels) have received considerable attention recently as effective stimuli-transforming vectors for a range of drug delivery applications. Considering this fact, the present work involves systematic formulation development, optimization, functional evaluation and ex vivo performance of thermosensitive soluble gels containing Dexamethasone 21-phosphate disodium salt (DXN) as the model therapeutic. A series of in situ gel-forming systems comprising the thermoreversible polymer poloxamer-407 (P407), along with hydroxypropyl methyl cellulose (HPMC) and chitosan were first formulated. The optimized soluble gels were evaluated for their potential to promote greater retention at the mucosal surface, for improved therapeutic efficacy, compared to existing solution/suspension-based steroid formulations used clinically. Optimized soluble gels demonstrated a desirable gelation temperature with Newtonian fluid behaviour observed under storage conditions (4-8 degrees C), and pseudoplastic fluid behaviour recorded at nasal cavity/sinus temperature ( approximately 34 degrees C). The in vitro characterization of formulations including rheological evaluation, textural analysis and mucoadhesion studies of the gel form were investigated. Considerable improvement in mechanical properties and mucoadhesion was observed with incorporation of HPMC and chitosan into the gelling systems. The lead poloxamer-based soluble gels, PGHC4 and PGHC7, which were carried through to ex vivo permeation studies displayed extended drug release profiles in conditions mimicking the human nasal cavity, which indicates their suitability for treating a range of conditions affecting the nasal cavity/sinuses.

Mucoadhesivity and release properties of quaternary ammonium-chitosan conjugates and their nanoparticulate supramolecular aggregates: an NMR investigation.[Pubmed:24368100]

Int J Pharm. 2014 Jan 30;461(1-2):489-94.

Selective relaxation rate measurements effectively proved the affinity of Dexamethasone 21-phosphate disodium salt for quaternary ammonium-chitosan conjugates, their thiolated derivatives and the corresponding nanostructured aggregates. Affinity was also probed by dynamic dialysis. The release profile of dexamethasone loaded nanoparticles was defined by quantitative NMR and interrupted dialysis experiments, and mucoadhesivity of empty nanoparticles was effectively probed by selective relaxation rate measurements.

[Quantitative interpretation of dexamethasone pharmacokinetics in human inner ear perilymph using computer simulations].[Pubmed:21322932]

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2010 Nov;24(22):1040-3.

OBJECTIVE: To study the dexamethasone pharmacokinetics of human inner ear perilymph under different drug administration using computer simulations. METHOD: The dexamethasone pharmacokinetics in guinea pigs inner ear perilymph under an intratympanic application with high-performance liquid chromatography. Dexamethasone pharmacokinetics in the guinea pigs cochlear fluid were simulated with a computer model, the Washington University Cochlear Fluids Simulator, version 1.6 and the best Simulations parameters to the experimental data could be obtain. With best Simulations parameters based on the experimental data, seven kinds application protocols were designed for human inner ear perilymph. RESULT: After an intratympanic application dose of 0.5% dexamethasone 150 ml in guinea pigs, the T(1/2K) was (2.918 +/- 0.089) h, and Cmax was (231.25 +/- 6.89) microg/L. The best Simulations parameters were that concentration of the Dexamethasone 21-phosphate disodium salt was 0.5% and the formula weight was 516, as well as drug diffusion coefficient was 0.6939 x 10(-5) cm2/s and round window permeability was 2.2 x 10(-11) cm/s while drug clearance half time was 175 minutes and scala tympaniscala vestibuli communication was 45 minutes. After an intratympanic application dose of 0.5% dexamethasone 500 mL, which the applied drug stayed in contact with the round window membrane for 15, 30, 60 and 120 minutes, the Cmax was 32.8, 64.3, 122.6 and 203.3 microg/L and the AUC was 116.5, 229.1, 423.6 and 759.2 microg/(h x L), respectively. After an intratympanic application dose of 0.5%, 1%, 2% and 4% dexamethasone 500 ml, which the applied drug stayed in contact with the round window membrane for 30 minutes respectively, the Cmax was 64.3, 127.3, 255.4 and 575.6 microg/L respectively and the AUC was 229.1, 462.8, 920.59 and 1525.2 microg/(h x L), respectively. CONCLUSION: The dexamethasone pharmacokinetics in human inner ear perilymph by computer simulations was reported. As the time contact with the round window membrane increased, the inner ear perilymph concentration of dexamethasone increased. As the concentration of dexamethasone increased, the inner ear perilymph concentration of drug increased.