Bioadhesive polymeric nanoparticles as strategy to improve the treatment of yeast infections in oral cavity: in-vitro and ex-vivo studies

2018 ◽  
Vol 104 ◽  
pp. 19-31 ◽  
Author(s):  
Luís Roque ◽  
Pedro Castro ◽  
Jesús Molpeceres ◽  
Ana S. Viana ◽  
Amílcar Roberto ◽  
...  
Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 675 ◽  
Author(s):  
Mariana Amaral ◽  
Ana Sofia Martins ◽  
José Catarino ◽  
Pedro Faísca ◽  
Pradeep Kumar ◽  
...  

Currently, insulin can only be administered through the subcutaneous route. Due to the flaws associated with this route, it is of interest to orally deliver this drug. However, insulin delivered orally has several barriers to overcome as it is degraded by the stomach’s low pH, enzymatic content, and poor absorption in the gastrointestinal tract. Polymers with marine source like chitosan are commonly used in nanotechnology and drug delivery due to their biocompatibility and special features. This work focuses on the preparation and characterization of mucoadhesive insulin-loaded polymeric nanoparticles. Results showed a suitable mean size for oral administration (<600 nm by dynamic laser scattering), spherical shape, encapsulation efficiency (59.8%), and high recovery yield (80.6%). Circular dichroism spectroscopy demonstrated that protein retained its secondary structure after encapsulation. Moreover, the mucoadhesive potential of the nanoparticles was assessed in silico and the results, corroborated with ex-vivo experiments, showed that using chitosan strongly increases mucoadhesion. Besides, in vitro and in vivo safety assessment of the final formulation were performed, showing no toxicity. Lastly, the insulin-loaded nanoparticles were effective in reducing diabetic rats’ glycemia. Overall, the coating of insulin-loaded nanoparticles with chitosan represents a potentially safe and promising approach to protect insulin and enhance peroral delivery.


2020 ◽  
Vol 17 (11) ◽  
pp. 4189-4200
Author(s):  
Kleopatra Kalouta ◽  
Mai Bay Stie ◽  
Christian Janfelt ◽  
Ioannis S. Chronakis ◽  
Jette Jacobsen ◽  
...  

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii202-ii202
Author(s):  
John Will ◽  
Emily Thompson ◽  
Megan Harrigan ◽  
James Smyth ◽  
Zhi Sheng ◽  
...  

Abstract Glioblastoma (GBM) is the most common and aggressive primary adult brain tumor in the US. The current treatment regimen for GBM still retains an alarmingly poor prognosis, with median survival of only 14.6 months. Failure to generate more effective treatment strategies is due to the infiltrative nature of GBM tumor cells, which hinders complete surgical resection, and cellular heterogeneity within GBM tumors, with a sub-population of glioma stem cells (GSCs) resistant to irradiation treatment and chemotherapeutic agents including temozolomide. As a result, all treated GBM patients will experience tumor recurrence, highlighting the need for novel approaches in targeting such refractory tumor cell populations to successfully treat GBM tumors and prevent recurrence. Using super resolution localization microscopy, we have identified that increased interaction of connexin43 (Cx43) with microtubules in GSCs confers tumorigenic behavior to these cells. We employed a Cx43 mimetic peptide named JM2 (juxtamembrane 2) that encompasses the microtubule binding sequence of the Cx43 carboxy-terminus. This peptide drug efficiently and specifically disrupts the interaction of Cx43 with microtubules and limits GSC survival, proliferation, and migration, without affecting normal human astrocytes. Next, we implemented the therapeutic strategy of JM2 encapsulation within biodegradable polymeric nanoparticles (NPs) to reduce administration frequency and patient discomfort, and increase peptide stability and activity. We confirmed sustained release of JM2 from these poly(lactic-co-glycolic) acid biodegradable NPs, and JM2 bioactivity through disruption of Cx43 interaction with microtubules. Administration of JM2-NPs inhibits GSC-derived neurosphere formation in vitro and patient GBM-derived organoid growth ex vivo. Finally, using an orthotopic xenograft brain tumor mouse model, we demonstrate in vivo that JM2-NPs significantly decrease the number of GSCs within brain tumors, and inhibit the formation of highly invasive GBM tumors. Our findings on generation of JM2-NPs to target GSC survival lays the foundation for future clinical trials in newly diagnosed GBM patients.


2015 ◽  
Vol 128 ◽  
pp. 448-456 ◽  
Author(s):  
Mohammad Tariq ◽  
Md. Aftab Alam ◽  
Anu T. Singh ◽  
Zeenat Iqbal ◽  
Amulya K. Panda ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Neeraj Mittal ◽  
Gurpreet Kaur

In the present investigation, an attempt was made to formulate timolol maleate (TML) loaded polymeric nanoparticles of flax seed gum (FX) and chitosan (CH) for ocular delivery using ionic gelation method. The process of nanoparticle preparation was optimized using 2-factor, 3-level central composite experimental design. The optimal concentration of FX and CH that yielded nanoparticles with minimum particle size (267.06 ± 8.65 nm) and maximum encapsulation efficiency (74.96 ± 4.78%) was found to be 0.10% w/v and 0.08% w/v, respectively. The formulated nanoparticles revealed considerable bioadhesive strength and exhibited sustained release of drug in in vitro diffusion studies. The ex vivo transcorneal penetration study revealed higher corneal penetration of TML compared to marketed eye drops. The confocal scanning laser microscopy (CSLM) studies also confirmed the ability of nanoparticles to penetrate into deeper layers of cornea. The histopathological studies revealed corneal biocompatibility of nanoparticles. The nanoparticles were found to reduce the intra ocular pressure (IOP) in rabbits for prolonged period when compared to conventional eye drops. The results of the present study suggested a promising role of polymeric nanoparticles for ocular drug delivery in treatment of glaucoma.


Nanomaterials ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2538
Author(s):  
Aishah E. Albalawi ◽  
Abdullah D. Alanazi ◽  
Parastoo Baharvand ◽  
Maryam Sepahvand ◽  
Hossein Mahmoudvand

Since there is no potential, effective vaccine available, treatment is the only controlling option against hydatid cyst or cystic echinococcosis (CE). This study was designed to systematically review the in vitro, in vivo, and ex vivo effects of nanoparticles against hydatid cyst. The study was carried out based on the 06- PRISMA guideline and registered in the CAMARADES-NC3Rs Preclinical Systematic Review and Meta-analysis Facility (SyRF) database. The search was performed in five English databases, including Scopus, PubMed, Web of Science, EMBASE, and Google Scholar without time limitation for publications around the world about the protoscolicdal effects of all the organic and inorganic nanoparticles without date limitation in order to identify all the published articles (in vitro, in vivo, and ex vivo). The searched words and terms were: “nanoparticles”, “hydatid cyst”, “protoscoleces”, “cystic echinococcosis”, “metal nanoparticles”, “organic nanoparticles”, “inorganic nanoparticles, “in vitro”, ex vivo”, “in vivo”. Out of 925 papers, 29 papers including 15 in vitro (51.7%), 6 in vivo (20.7%), ex vivo 2 (6.9%), and 6 in vitro/in vivo (20.7%) up to 2020 met the inclusion criteria for discussion in this systematic review. The results demonstrated the most widely used nanoparticles in the studies were metal nanoparticles such as selenium, silver, gold, zinc, copper, iron nanoparticles (n = 8, 28.6%), and metal oxide nanoparticles such as zinc oxide, titanium dioxide, cerium oxide, zirconium dioxide, and silicon dioxide (n = 8, 28.6%), followed by polymeric nanoparticles such as chitosan and chitosan-based nanoparticles (n = 7, 25.0%). The results of this review showed the high efficacy of a wide range of organic and inorganic NPs against CE, indicating that nanoparticles could be considered as an alternative and complementary resource for CE treatment. The results demonstrated that the most widely used nanoparticles for hydatid cyst treatment were metal nanoparticles and metal oxide nanoparticles, followed by polymeric nanoparticles. We found that the most compatible drugs with nanoparticles were albendazole, followed by praziquantel and flubendazole, indicating a deeper understanding about the synergistic effects of nanoparticles and the present anti-parasitic drugs for treating hydatid cysts. The important point about using these nanoparticles is their toxicity; therefore, cytotoxicity as well as acute and chronic toxicities of these nanoparticles should be considered in particular. As a limitation, in the present study, although most of the studies have been performed in vitro, more studies are needed to confirm the effect of these nanoparticles as well as their exact mechanisms in the hydatid cyst treatment, especially in animal models and clinical settings.


VASA ◽  
2005 ◽  
Vol 34 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Brunner-La Rocca ◽  
Schindler ◽  
Schlumpf ◽  
Saller ◽  
Suter

Background: Previous studies showed an anti-atherosclerotic effect of PADMA 28, an herbal formula based on Tibetan medicine. As the mechanisms of action are not fully understood, we investigated whether PADMA 28 may lower blood lipids and lipid oxidisability, and affect early endothelial dysfunction. Patients and methods: Sixty otherwise healthy subjects with total cholesterol ≥5.2 mmol/l and < 8.0 mmol/l were randomly assigned to placebo or PADMA 28, 3 x 2 capsules daily, for 4 weeks (double-blind). Blood lipids (total, LDL-, and HDL-cholesterol, triglycerides, Apo-lipoprotein A1 and B) and ex vivo lipid oxidisability were measured before and after treatment. In a subset of 24 subjects, endothelial function was assessed using venous occlusion plethysmography with intraarterial infusion of acetylcholine. Isolated LDL and plasma both untreated and pre-treated with PADMA 28 extract were oxidised by the radical generator AAPH. Conjugated diene formation was measured at 245 nm. Results: Blood lipids did not change during the study in both groups. In contrast to previous reports in mild hypercholesterolaemia, no endothelial dysfunction was seen and, consequently, was not influenced by therapy. Ex vivo blood lipid oxidisability was significantly reduced with PADMA 28 (area under curve: 5.29 ± 1.62 to 4.99 ± 1.46, p = 0.01), and remained unchanged in the placebo group (5.33 ± 1.88 to 5.18 ± 1.78, p > 0.1). This effect persisted one week after cessation of medication. In vitro experiments confirmed the prevention of lipid peroxidation in the presence of PADMA 28 extracts. Persistent protection was also seen for LDL isolated from PADMA 28-pretreated blood after being subjected to rigorous purification. Conclusions: This study suggests that the inhibition of blood lipid oxidisability by PADMA 28 may play a role in its anti-atherosclerotic effect.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


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