Optimization, Biopharmaceutical Profile and Therapeutic Efficacy of Pioglitazone-loaded PLGA-PEG Nanospheres as a Novel Strategy for Ocular Inflammatory Disorders

Silva-Abreu, Marcelle; Calpena, Ana Cristina; Espina, Marta; Silva, Amélia M.; Gimeno, A.L.; Egea, M.A.; García, María L.

doi:10.1007/s11095-017-2319-8

Cited by 30 publications

(33 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…After previous factorial design, the PGZ-NPs showed a size around 160.0 ± 1.3 nm with PI values in the range of monodisperse systems (PI < 0.1) and high association efficiency (≈92%). Moreover, the ZP was −13.9 mV, which is indicative of the stability of these systems [41].…”

Section: Resultsmentioning

confidence: 99%

“…The physicochemical evaluation of this formulation showed favorable properties for the penetration of the drug across the blood-brain barrier (BBB) and the delivery of the drug in a controlled and sustained manner. Such advantages include small size (160.0 ± 1.3 nm), high association efficiency (≈92%), and good stability [41,46]. In addition, NPs are generally advantageous because of their good biocompatibility, capacity to adjust drug release, and remarkable enhancement of efficacy and bioavailability [29,47,48].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative Study of Ex Vivo Transmucosal Permeation of Pioglitazone Nanoparticles for the Treatment of Alzheimer’s Disease

et al. 2018

Self Cite

View full text Add to dashboard Cite

Pioglitazone has been reported in the literature to have a substantial role in the improvement of overall cognition in a mouse model. With this in mind, the aim of this study was to determine the most efficacious route for the administration of Pioglitazone nanoparticles (PGZ-NPs) in order to promote drug delivery to the brain for the treatment of Alzheimer’s disease. PGZ-loaded NPs were developed by the solvent displacement method. Parameters such as mean size, polydispersity index, zeta potential, encapsulation efficacy, rheological behavior, and short-term stability were evaluated. Ex vivo permeation studies were then carried out using buccal, sublingual, nasal, and intestinal mucosa. PGZ-NPs with a size around of 160 nm showed high permeability in all mucosae. However, the permeation and prediction parameters revealed that lag-time and vehicle/tissue partition coefficient of nasal mucosa were significantly lower than other studied mucosae, while the diffusion coefficient and theoretical steady-state plasma concentration of the drug were higher, providing biopharmaceutical results that reveal more favorable PGZ permeation through the nasal mucosa. The results suggest that nasal mucosa represents an attractive and non-invasive pathway for PGZ-NPs administration to the brain since the drug permeation was demonstrated to be more favorable in this tissue.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparative Study of Ex Vivo Transmucosal Permeation of Pioglitazone Nanoparticles for the Treatment of Alzheimer’s Disease

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…The conditions for NP production were optimized in a factorial design 26 ( Figure S1). Three independent variables (PGZ, PLGA-PEG and Tw 80 concentrations) and four dependent variables (average particle size [Z av ], polydispersity index [PI], zeta potential [ZP] and entrapment efficiency [EE] were studied.…”

Section: Optimization and Characterization Of Npsmentioning

confidence: 99%

“…PLGA is an FDA-approved co-polymer used successfully for delivery to different tissues, including the brain. 19,[25][26][27] The attachment of specific ligands to the surface of NPs makes the delivery of drugs to CNS more targeted and may enhance the limited BBB penetration of therapeutic compounds. For instance, polyethylene glycol (PEG) can functionalize NPs to increase their plasma residence time, preventing their removal by mononuclear phagocytes.…”

Section: Introductionmentioning

confidence: 99%

PPARγ agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer’s disease: in vitro and in vivo studies

Silva-Abreu¹,

Calpena²,

Andrés‐Benito³

et al. 2018

IJN

Self Cite

View full text Add to dashboard Cite

ObjectiveThe first aim of this study was to develop a nanocarrier that could transport the peroxisome proliferator-activated receptor agonist, pioglitazone (PGZ) across brain endothelium and examine the mechanism of nanoparticle transcytosis. The second aim was to determine whether these nanocarriers could successfully treat a mouse model of Alzheimer’s disease (AD).MethodsPGZ-loaded nanoparticles (PGZ-NPs) were synthesized by the solvent displacement technique, following a factorial design using poly (lactic-co-glycolic acid) polyethylene glycol (PLGA-PEG). The transport of the carriers was assessed in vitro, using a human brain endothelial cell line, cytotoxicity assays, fluorescence-tagged nanocarriers, fluorescence-activated cell sorting, confocal and transmission electron microscopy. The effectiveness of the treatment was assessed in APP/PS1 mice in a behavioral assay and by measuring the cortical deposition of β-amyloid.ResultsIncorporation of PGZ into the carriers promoted a 50x greater uptake into brain endothelium compared with the free drug and the carriers showed a delayed release profile of PGZ in vitro. In the doses used, the nanocarriers were not toxic for the endothelial cells, nor did they alter the permeability of the blood–brain barrier model. Electron microscopy indicated that the nanocarriers were transported from the apical to the basal surface of the endothelium by vesicular transcytosis. An efficacy test carried out in APP/PS1 transgenic mice showed a reduction of memory deficit in mice chronically treated with PGZ-NPs. Deposition of β-amyloid in the cerebral cortex, measured by immunohistochemistry and image analysis, was correspondingly reduced.ConclusionPLGA-PEG nanocarriers cross brain endothelium by transcytosis and can be loaded with a pharmaceutical agent to effectively treat a mouse model of AD.

show abstract

“…It can improve the permeability, mucosal adhesion, sustained release, and controlled release properties of different drug molecules that, in turn, improves the bioavailability of the drug. Silva-Abreu et al [8] investigated the in vitro scleral permeability of pioglitazone-loaded PLGA nanoparticles to demonstrate that the nanoparticles had better permeability and could be more effective against inflammation. Kalam et al [9] examined the pharmacokinetics of aqueous extracts of tacrolimus PLGA nanoparticles after aqueous eye drops.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of 2-HP-β-cyclodextrin-PLGA nanoparticle complexes for potential use as ocular drug delivery vehicles

Wen

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

Aim: 2-HP-b-cyclodextrin-PLGA nanoparticle complexes were prepared to enhance the aqueous humour delivery of Triamcinolone acetonide. Materials & methods: Drug-loaded 2-HP-b-CD/PLGA nanoparticle complexes prepared by adapting a quasi-emulsion solvent evaporation technique. In vitro drug release, in vitro transcorneal permeation study, histopathological study and in vivo transcorneal penetration of PLGA nanoparticles and 2-HP-b-CD/PLGA nanoparticle complexes were evaluated. Results: Particle size distributions of 2-HP-b-CD/PLGA nanoparticle complexes were 149.4 ± 3.7 nm and presented stable system. Corneal penetration studies revealed steady sustained drug release (Firstorder); 2-HP-b-CD/PLGA nanoparticle complexes increased ocular bioavailability by increasing dispersion in the tear film and improving drug release. Conclusion: 2-HP-b-CD/PLGA nanoparticle complex formulation is a promising alternative to conventional eye drops.

show abstract

Optimization, Biopharmaceutical Profile and Therapeutic Efficacy of Pioglitazone-loaded PLGA-PEG Nanospheres as a Novel Strategy for Ocular Inflammatory Disorders

Abstract: The in vivo anti-inflammatory efficacy of developed PGZ-NSs indicates this colloidal system could constitute a new approach to prevent ocular inflammation.

Cited by 30 publications

References 35 publications

Comparative Study of Ex Vivo Transmucosal Permeation of Pioglitazone Nanoparticles for the Treatment of Alzheimer’s Disease

Comparative Study of Ex Vivo Transmucosal Permeation of Pioglitazone Nanoparticles for the Treatment of Alzheimer’s Disease

PPARγ agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer’s disease: in vitro and in vivo studies

Characterisation of 2-HP-β-cyclodextrin-PLGA nanoparticle complexes for potential use as ocular drug delivery vehicles

Contact Info

Product

Resources

About

Optimization, Biopharmaceutical Profile and Therapeutic Efficacy of Pioglitazone-loaded PLGA-PEG Nanospheres as a Novel Strategy for Ocular Inflammatory Disorders

Abstract: The in vivo anti-inflammatory efficacy of developed PGZ-NSs indicates this colloidal system could constitute a new approach to prevent ocular inflammation.

Cited by 30 publications

References 35 publications

Comparative Study of Ex Vivo Transmucosal Permeation of Pioglitazone Nanoparticles for the Treatment of Alzheimer’s Disease

Comparative Study of Ex Vivo Transmucosal Permeation of Pioglitazone Nanoparticles for the Treatment of Alzheimer’s Disease

PPAR&gamma; agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer&rsquo;s disease: in vitro and in vivo studies

Characterisation of 2-HP-β-cyclodextrin-PLGA nanoparticle complexes for potential use as ocular drug delivery vehicles

Contact Info

Product

Resources

About

PPARγ agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer’s disease: in vitro and in vivo studies