Mechanism of Hydrogen Sulfide Drug-Loaded Nanoparticles Promoting the Repair of Spinal Cord Injury in Rats Through Mammalian Target of Rapamycin/Signal Transducer and Activator of Transcription 3 Signaling Pathway

2021 ◽  
Vol 13 (9) ◽  
pp. 1691-1698
Author(s):  
Hongzhe Liu ◽  
Kai Tong ◽  
Ziyi Zhong ◽  
Gang Wang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Particle Size ◽  
Dispersion Coefficient ◽  
Drug Loading ◽  
Average Particle Size ◽  
Mammalian Target Of Rapamycin ◽  
Average Particle ◽  
Recovery Effect ◽  
Cord Injury

To explore the effect of hydrogen sulfide (H2S) drug-loaded nanoparticles (H2S-NPs) on the mTOR/STAT3 signaling pathway in rats and its mechanism on repair of spinal cord injury (SCI), a new H2S-NP (G16MPG-ADT) was prepared and synthesized. The rats were selected as the research objects to explore the mechanism of SCI repair. The G16MPG-ADT NPs were evaluated by average particle size (APS), dispersion coefficient (DC), drug loading content (DLC), drug loading efficacy (DLE), in vitro release (IV-R), and acute toxicity (AT). It was found that G16MPG-ADT nanoparticles had a uniform particle size distribution with a unimodal distribution, with an average particle size of 186.5 nm and a dispersion coefficient of 0.129; within the concentration range of 8~56 μg/L, there was a good linear relationship with the peak area; and the release rate of the nanoparticles within 16 h~32 h was higher than 50%. G16MPG-ADT NP injection treatment was performed on rats with SCI. Western blotting (WB) and immunofluorescence staining were adopted to analyze the expression levels of mammalian target of rapamycin (mTOR) and signal transducers and activators of transcription (STAT3) protein and the growth of neurites. It was found that G16MPG-ADT can increase mTOR and STAT3 protein levels and promote nerve growth after SCI. Finally, the Basso, Beattie and Bresnahan locomotor rating (BBB) score was to evaluate the recovery effect of rats after treatment. It was found that the recovery effect was excellent after G16MPG-ADT treatment. In summary, G16MPG-ADT has a good effect on SCI repair in rats and can be promoted in the clinic.

Formulating SLN and NLC as Innovative Drug Delivery Systems for Non-Invasive Routes of Drug Administration

2020 ◽  
Vol 27 (22) ◽  
pp. 3623-3656 ◽  
Author(s):  
Bruno Fonseca-Santos ◽  
Patrícia Bento Silva ◽  
Roberta Balansin Rigon ◽  
Mariana Rillo Sato ◽  
Marlus Chorilli
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Drug Release ◽  
Drug Loading ◽  
Average Particle Size ◽  
Delivery Systems ◽  
Average Particle ◽  
Minor Importance ◽  
Routes Of Administration ◽  
Non Invasive

Colloidal carriers diverge depending on their composition, ability to incorporate drugs and applicability, but the common feature is the small average particle size. Among the carriers with the potential nanostructured drug delivery application there are SLN and NLC. These nanostructured systems consist of complex lipids and highly purified mixtures of glycerides having varying particle size. Also, these systems have shown physical stability, protection capacity of unstable drugs, release control ability, excellent tolerability, possibility of vectorization, and no reported production problems related to large-scale. Several production procedures can be applied to achieve high association efficiency between the bioactive and the carrier, depending on the physicochemical properties of both, as well as on the production procedure applied. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes Lipid-based nanocarriers (LNCs) versatile delivery system for various routes of administration. The route of administration has a significant impact on the therapeutic outcome of a drug. Thus, the non-invasive routes, which were of minor importance as parts of drug delivery in the past, have assumed added importance drugs, proteins, peptides and biopharmaceuticals drug delivery and these include nasal, buccal, vaginal and transdermal routes. The objective of this paper is to present the state of the art concerning the application of the lipid nanocarriers designated for non-invasive routes of administration. In this manner, this review presents an innovative technological platform to develop nanostructured delivery systems with great versatility of application in non-invasive routes of administration and targeting drug release.

scholarly journals Effect of soil textural characteristics on longitudinal dispersion in saturated porous media

2021 ◽  
Vol 69 (2) ◽  
pp. 161-170
Author(s):  
Mojtaba G. Mahmoodlu ◽  
Amir Raoof ◽  
Martinus Th. van Genuchten
Keyword(s):  
Particle Size ◽  
Dispersion Coefficient ◽  
Average Particle Size ◽  
Longitudinal Dispersion ◽  
Average Particle ◽  
Sand Sample ◽  
Average Pore ◽  
Advection Dispersion ◽  
Strong Positive Relationship

Abstract This study focuses on the effects of soil textural heterogeneity on longitudinal dispersion under saturation conditions. A series of solute transport experiments were carried out using saturated soil columns packed with two filter sands and two mixtures of these sands, having d50 values of 95, 324, 402, and 480 µm, subjected to four different steady flow rates. Values of the dispersion coefficient (D) were estimated from observed in-situ distributions of calcium chlo-ride, injected as a short nonreactive tracer pulse, at four different locations (11, 18, 25, 36 cm). Analyses of the observed distributions in terms of the standard advection-dispersion equation (ADE) showed that D increased nonlinearly with travel distance and higher Peclet numbers+. The dispersion coefficient of sand sample S1 with its largest average particle size (d 50) was more affected by the average pore-water velocity than sample S4 having the smallest d 50. Results revealed that for a constant velocity, D values of sample S1 were much higher than those of sample S4, which had the smallest d 50. A correlation matrix of parameters controlling the dispersion coefficient showed a relatively strong positive relationship between D and the Peclet number. In contrast, almost no correlation was evident between D and porosity as well as grain size. The results obtained with the four sandy matrices were consistent and proved that the dispersion coefficient depends mainly on the particle size.

scholarly journals Sodium Alginate Nanoparticles of Isoniazid: Preparation and Evaluation

2019 ◽  
Vol 11 (06) ◽  
Author(s):  
Sumit Kumar ◽  
Dinesh Chandra Bhatt
Keyword(s):  
Particle Size ◽  
Sodium Alginate ◽  
Encapsulation Efficiency ◽  
Drug Loading ◽  
Average Particle Size ◽  
Average Particle ◽  
In Vitro Drug Release ◽  
Ionotropic Gelation ◽  
Preparation And Evaluation

Fabrication and evaluation of the Isoniazid loaded sodium alginate nanoparticles (NPs) was main objective of current investigation. These NPs were engineered using ionotropic gelation technique. The NPs fabricated, were evaluated for average particle size, encapsulation efficiency, drug loading, and FTIR spectroscopy along with in vitro drug release. The particle size, drug loading and encapsulation efficiency of fabricated nanoparticles were ranging from 230.7 to 532.1 nm, 5.88% to 11.37% and 30.29% to 59.70% respectively. Amongst all batches studied formulation F-8 showed the best sustained release of drug at the end of 24 hours.

scholarly journals Investigation on the Motor Recovery Effect of a Self-Assembling Nanofiber in the Spinal Cord Injury Model in Rat

2014 ◽  
Vol 2 (2) ◽  
pp. 41-46 ◽  
Author(s):  
Shima Tavakol ◽  
Hadi Aligholi ◽  
Arezou Eshaghabadi ◽  
Mostafa Modarres Mousavi ◽  
Jafar Ai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Recovery ◽  
Recovery Effect ◽  
Self Assembling ◽  
Spinal Cord Injury Model ◽  
Injury Model ◽  
Cord Injury

scholarly journals Bio Pharmaceutics Classification System (BCS) Class IV Drug Nanoparticles: Quantum Leap to Improve Their Therapeutic Index

2018 ◽  
Vol 8 (4) ◽  
pp. 617-625 ◽  
Author(s):  
Sachin Kumar ◽  
Ramneek Kaur ◽  
Rashi Rajput ◽  
Manisha Singh
Keyword(s):  
Particle Size ◽  
Classification System ◽  
Drug Loading ◽  
Average Particle Size ◽  
Therapeutic Index ◽  
Diffusion Profile ◽  
Average Particle ◽  
Linear Diffusion ◽  
Quantum Leap ◽  
Class Iv

Purpose: Biopharmaceutics classification system (BCS) class IV compounds, exhibits least oral bioavailability, low solubility and intestinal permeability among all pharmaceutical classes of drugs. Thus, these drugs need more compatible and efficient delivery system. Since, their solubility in various medium, remains a limitation so, polymeric nano coacervates based drug loading with modified approach for them may prove to be a solution ahead. Therefore, in present study Chitosan is opted for encapsulating the BCS class IV drug (Hydrochlorothiazide) to attain better stability, enhanced permeability and lower toxicity. Methods: For this study, Hydrochlorothiazide (HCTZ) was opted for formulating chitosan based nano-coacervate system. Results: Optimized HCTZ nanocoacervates exhibited the average particle size of 91.39 ± 0.75 nm with Poly-dispersity index score of 0.159 ± 0.01, indicating homogeneity of colloidal solution. Zeta potential and encapsulation efficiency of HCTZ nanocoacervates were recorded as -18.9 ± 0.8 mV and 76.69 ± 0.82 % respectively. Further, from TEM and SEM evaluation the average particle size for the same were found in conformity (35-50 nm), with almost spherical morphology. Also, the EDX (Electron Dispersive X-ray) spectrometry and FT – IR analysis of optimized formulation indicated the balanced chemical composition and interaction between the polymeric molecules. The HCTZ nano coacervates showed the linear diffusion profile through the dialysis membrane. Conclusion: We can conclude from the present study that the optimized HCTZ nano coacervates may prove to be a suitable potential option for effective delivery of BCS class IV drugs.

Therapeutic Effects of Paclitaxel Loaded Polyethylene Glycol-Polylactic Acid-Glycolic Acid Copolymer Nanoparticles on Pancreatic Cancer in Rats

2020 ◽  
Vol 20 (12) ◽  
pp. 7271-7275
Author(s):  
Yu Fu ◽  
Ludong Tan ◽  
Lingyu Meng ◽  
Xuexue Lei
Keyword(s):  
Pancreatic Cancer ◽  
Flow Cytometry ◽  
Particle Size ◽  
Drug Loading ◽  
Average Particle Size ◽  
Pancreatic Cancer Cell Line ◽  
Human Pancreatic Cancer ◽  
Average Particle ◽  
Therapeutic Effects ◽  
Significant Difference

To establish a simple and safe method for the preparation of paclitaxel PEG-PLGA nanoparticles emulsified in tpgs (PTX-pegpllga-np), for high drug loading; and to study its effect on proliferation and apoptosis of human pancreatic cancer cell line MIAPACA-2. PTX-PEG-PLGA-NP was prepared by one-step precipitation, using tpgs as emulsifier. The drug loading and particle size were used as an index to optimize the formulation, and the physical and chemical properties such as in vitro release and stability were characterized. The uptake of fluorescein coumarin 6 (C6) loaded PEG-PLGA-NP by MIAPACA-2 cells was observed by fluorescence microscope, and the growth and apoptosis of MIAPACA-2 cells after PTX-PEG-PLGA-NP were detected by MTT and flow cytometry respectively. The entrapment efficiency of the nanoparticles was 90.26%, the drug loading was 10.13%, the average particle size was 92.3±3.1 nm, and the zeta potential was 10.48±1.54 mV. The cumulative releases of nano preparation and general preparation (Taxol injection) in four hours were 25.9% and 98.5%, respectively; and the former had a strong sustained-release effect. The results of cell uptake experiments showed that the uptake of c6-PEG-PLGA-NP by MIAPACA-2 cells increased gradually with time. MTT results showed that PTX-PEG-PLGA-NP had no significant difference in the inhibition rate of MIAPACA-2 cells compared with PTX group. Flow cytometry showed that PTX-PEG-PLGAnp was superior better than PTX in inducing apoptosis in MIAPACA-2 cells. The tpgs emulsification method is simple and environment-friendly. The paclitaxel loaded nanoparticles prepared through the optimization of the formulation have large drug loading capacity and uniform particle size, which can target the pancreatic cancer MIAPACA-2 cells, and do not weaken its ability to inhibit the growth of MIAPACA-2 cells. The nanoparticles also induce apoptosis in cancer MIAPACA-2 cells, and could be used for further clinical treatment of pancreatic cancer.

scholarly journals Beneficial Effects of Resveratrol-Mediated Inhibition of the mTOR Pathway in Spinal Cord Injury

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jingying Zhou ◽  
Xue Huo ◽  
Benson O. A. Botchway ◽  
Luyao Xu ◽  
Xiaofang Meng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
High Rate ◽  
Mtor Signaling Pathway ◽  
Beneficial Effects ◽  
Cord Injury

Spinal cord injury (SCI) causes a high rate of morbidity and disability. The clinical features of SCI are divided into acute, subacute, and chronic phases according to its pathophysiological events. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in cell death and inflammation in the acute phase and neuroregeneration in the subacute/chronic phases at different times. Resveratrol has the potential of regulating cell growth, proliferation, metabolism, and angiogenesis through the mTOR signaling pathway. Herein, we explicate the role of resveratrol in the repair of SCI through the inhibition of the mTOR signaling pathway. The inhibition of the mTOR pathway by resveratrol has the potential of serving as a neuronal restorative mechanism following SCI.

Abdominal Adiposity and Insulin Level Influence Lipoprotein Particle Size and Concentration in Spinal Cord Injury

2010 ◽  
Vol 42 ◽  
pp. 532
Author(s):  
Racine R. Emmons ◽  
Christopher M. Cirnigliaro ◽  
Steven C. Kirshblum ◽  
Marinella D. Galea ◽  
Ann M. Spungen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Particle Size ◽  
Insulin Level ◽  
Abdominal Adiposity ◽  
Lipoprotein Particle ◽  
Cord Injury ◽  
Lipoprotein Particle Size
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