Dexamethasone sodium phosphate loaded nanoparticles for prevention of nitrogen mustard induced corneal injury.

Nitrogen mustard (NM) is a potent vesicating chemical warfare agent that is primarily absorbed through skin, inhalation, or ocular surface. Ocular exposure of NM can cause acute to chronic keratopathy which can eventually lead to blindness. There is a current lack of effective countermeasures against ocular exposure of NM despite their imperative need. Herein, we aim to explore the sustained effect of Dexamethasone sodium phosphate (DSP)-loaded polymeric nanoparticles (PLGA-DSP-NP) following a single subconjunctival injection in the management and prevention of corneal injury progression upon exposure to NM. DSP is an FDA approved corticosteroid with proven anti-inflammatory properties. We formulated PLGA-DSP-NP with zinc chelation ion bridging method using PLGA polymer, with particles of approximately 250 nm and a drug loading of 6.5 wt%. Under in vitro sink conditions, PLGA-DSP-NP exhibited a sustained drug release for two weeks. Notably, in NM injured cornea, a single subconjunctival (SCT) injection of PLGA-DSP-NP outperformed DSP eyedrops (0.1%), DSP solution, placebo NP, and saline, significantly mitigating corneal neovascularization, ulceration, and opacity for the two weeks study period. Through PLGA-DSP-NP injection, sustained DSP release hindered inflammatory cytokine recruitment, angiogenic factors, and endothelial cell proliferation in the cornea. This strategy presents a promising localized corticosteroid delivery system to effectively combat NM-induced corneal injury, offering insights into managing vesicant exposure.

Chitosan -based nanoniosome for potential wound healing applications: Synergy of controlled drug release and antibacterial activity.

This study aims to develop a niosomal platform which can delivery drugs such as tetracycline hydrochloride (TCH) to treat bacterial infections in wounds. To this end, chitosan (CS) was used to obtain a controlled drug release and at the same time antibacterial activity. By design of experiments the niosome encapsulated TCH (TCH-Nio) were optimized for their particle size and encapsulation efficiency, followed by analysis of the release profile of TCH and stability of TCH-Nio and TCH-Nio@CS. The antibacterial activity and cytotoxicity of the fabricated nanoparticles were investigated as well. The release rate of TCH from TCH-Nio@CS in all conditions is less than TCH-Nio. In addition, higher temperature increases the release rate of drug from these formulations. The size, polydispersity index, and encapsulation efficacy of TCH-Nio and TCH-Nio@CS were more stable in 4 °C compared to 25 °C. TCH, TCH-Nio, and TCH-Nio@CS had MIC values of 7.82, 3.91, and 1.95 µg/mL for Escherichia coli, 3.91, 1.95, and 0.98 µg/mL for Pseudomonas aeruginosa, and 1.96, 0.98, and 0.49 µg/mL for Staphylococcus aureus, respectively. Coating of chitosan on niosome encapsulated TCH (TCH-Nio@CS) led to a reduced burst release of TCH from niosome (TCH-Nio), and enabled 2-fold higher antibacterial and anti-biofilm activity against the tested bacterial pathogens E. coli, P. aeruginosa and S. aureus, compared to the uncoated TCH-Nio, and 4-folder higher than the TCH solution, suggesting the synergetic effect of niosome encapsulation and chitosan coating. Moreover, the formulated niosomes displayed no in vitro toxicity toward the human foreskin fibroblast cells (HFF). Both TCH-Nio and TCH-Nio@CS were found to down-regulate the expression of certain biofilm genes, i.e., csgA, ndvB, and icaA in the tested bacteria, which might partially explain the improved antibacterial activity compared to TCH. The obtained results demonstrated that TCH-Nio@CS is capable of controlled drug release, leading to high antibacterial efficacy. The established platform of TCH-Nio@CS enlighten a clinic potential toward the treatment of bacterial infections in skin wounds, dental implants and urinary catheter.

An insight into gastrointestinal macromolecule delivery using physical oral devices.

Oral delivery is preferred over other routes of drug administration by both patients and physicians. The bioavailability of some therapeutics that are delivered via the oral route is restricted due to the protease- and bacteria-rich environment in the gastrointestinal tract, and by the pH variability along the delivery route. Given these harsh environments, the oral delivery of therapeutic macromolecules is complicated and remains challenging. Various formulation approaches, including the use of permeation enhancers and nanosized carriers, as well as chemical alteration of the drug structure, have been studied as ways to improve the oral absorption of macromolecular drugs. Nevertheless, the bioavailability of marketed oral peptide medicines is often relatively poor. This review highlights the most recent and promising physical methods for improving the oral bioavailability of macromolecules such as peptides. These methods include microneedle injections, high-speed stream injectors, magnetic drug targeting, expandable hydrogels, and iontophoresis. We highlight the potential and challenges of these new technologies, which may impact the future approaches used by pharmaceutical companies to create more efficient and safer orally administered macromolecules.

The Effect of Thermal-Treating on Drug Release from Sustained Release Alginate-Eudragit RS Matrices.

Purpose: The main objective of the present study was to develop the colonic delivery system for 5-aminosalicylic acid (5-ASA) as an anti-inflammatory drug. Methods: Matrix pellets containing various proportions of alginate, calcium and Eudragit® RS were prepared by extrusion-spheronization technique. Thermal treatment was used to investigate the effect of the curing process on the surface morphology, mechanical and physicochemical properties and in vitro drug release profile of pellets. Based on the obtained results optimal formulations were selected to coating by the Eudragit® RS and subjected to a subsequent continuous dissolution test. Results: Image analysis and also scanning electron microscopy results proved acceptable morphology of the pellets. The fourier transform infrared spectroscopy and differential scanning calorimetry studies ruled out any interactions between the formulation's components. Curing process did not alter the mechanical properties of pellets. The release rate of the drug from matrices was prolonged due to the decreased porosity of cured pellets. Furthermore, selected cured pellets which coated with Eudragit® RS, prevented undesired premature drug release. Conclusion: Formulation containing 17.5% calcium, 17.5% alginate, and a coating level of 10% demonstrated enhanced drug release so that provided resistance to acidic conditions, allowing complete drug release in alkaline pH, mimicking colonic environment. The slow and consistent drug release from this formulation could be used for treatment of a broader range of Inflammatory bowel disease (IBD) patients especially in whom colonic pH levels have been measured at lower than pH 7.0.

The Effect of Hematocrit and Nanoparticles Diameter on Hemodynamic Parameters and Drug Delivery in Abdominal Aortic Aneurysm with Consideration of Blood Pulsatile Flow.

BACKGROUND AND OBJECTIVE: The present article has simulated to investigate the efficient hemodynamic parameters, the drug persistence, and drug distribution on an abdominal aortic aneurysm. METHODS: Blood as a non-Newtonian fluid enters the artery acting as a real pulse waveform; its behavior is dependent on hematocrit and strain rate. In this simulation of computational fluid dynamic, magnetic nanoparticles of iron oxide which were in advance coated with the drug, are injected into the artery during a cardiac cycle. A two-phase model was applied to investigate the distribution of these carriers. RESULTS: The results are presented for different hematocrits and the nanoparticle diameter. It is observed that hematocrit significantly affects drug persistence, so that lower hematocrit incites more accumulation of the drug in the dilatation part of the artery. The better drug accumulation is noticed, at the higher wall shear stress. Although no considerable impact on the flow pattern and wall shear stress was found with various nanoparticle diameters, the smaller size of the nanoparticles results in a greater amount of drug augmentation in the aneurysm wall output. CONCLUSIONS: At the higher hematocrit levels, the blood resistance to drug delivery increases throughout the artery. Also, the drug accumulates less on the aneurysm wall and stays longer on the aneurysm wall. On the contrary, the drug accumulates more by decreasing hematocrit level and stays shorter on the aneurysm wall. Moreover, the maximum drug concentration is observed at the lowest hematocrit level and nanoparticle diameter; also, the diameter of nanoparticles imposes no significant effect on the vorticity and wall shear stress. It is seen that the increment of the hematocrit level reduces the strength of vorticity and increases the amount of wall shear stress in the dilatation segment of the artery. The shear stress at three points of the dilatation wall is extreme, where the maximum density of nanoparticles occurs.