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

Silva-Abreu, Marcelle; Espinoza, Lupe Carolina; Halbaut, Lyda; Espina, Marta; García, María L.; Calpena, Ana Cristina

doi:10.3390/polym10030316

Cited by 38 publications

(20 citation statements)

References 63 publications

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“…Moreover, the theoretical human steady-state plasma concentration ( C ss ) of drug, which estimates the concentration of drug that could be reached in the blood after nasal administration, was obtained using Equation (2). Css=Jss AClp where J ss is the flux, A is the hypothetical area of application (150 cm 2 for nasal mucosa), and Clp is the plasmatic clearance (human Clp value for DPZ according to the Food and Drug Administration is 10 L/h) [28].…”

Section: Methodsmentioning

confidence: 99%

Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil

et al. 2019

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Donepezil (DPZ) is widely used in the treatment of Alzheimer’s disease in tablet form for oral administration. The pharmacological efficacy of this drug can be enhanced by the use of intranasal administration because this route makes bypassing the blood–brain barrier (BBB) possible. The aim of this study was to develop a nanoemulsion (NE) as well as a nanoemulsion with a combination of bioadhesion and penetration enhancing properties (PNE) in order to facilitate the transport of DPZ from nose-to-brain. Composition of NE was established using three pseudo-ternary diagrams and PNE was developed by incorporating Pluronic F-127 to the aqueous phase. Parameters such as physical properties, stability, in vitro release profile, and ex vivo permeation were determined for both formulations. The tolerability was evaluated by in vitro and in vivo models. DPZ-NE and DPZ-PNE were transparent, monophasic, homogeneous, and physically stable with droplets of nanometric size and spherical shape. DPZ-NE showed Newtonian behavior whereas a shear thinning (pseudoplastic) behavior was observed for DPZ-PNE. The release profile of both formulations followed a hyperbolic kinetic. The permeation and prediction parameters were significantly higher for DPZ-PNE, suggesting the use of polymers to be an effective strategy to improve the bioadhesion and penetration of the drug through nasal mucosa, which consequently increase its bioavailability.

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Section: Methodsmentioning

confidence: 99%

Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil

et al. 2019

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“…Parameters such as size, polydispersity index (PDI) and Zeta Potential (ZP) were evaluated to confirm the stability with a Zetasizer Nano ZS (Malvern Instruments, Malvern, UK). Additionally, the encapsulation efficiency (EE) was determined by the indirect method [ 47 ].…”

Section: Methodsmentioning

confidence: 99%

“…The new formulations improved the biopharmaceutical profile of the drugs. In particular, PGZ-NPs of PLGA-PEG were formulated for eye treatment and also for delivery to the brain [ 12 , 47 ]. These nanosystems were optimized, characterized, and their anti-inflammatory activity, as well as their tolerance, were demonstrated for in vitro, ex vivo, and in vivo animal models.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of an HPLC–MS/MS Method for Pioglitazone from Nanocarriers Quantitation in Ex Vivo and In Vivo Ocular Tissues

et al. 2021

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Pioglitazone (PGZ) is an oral anti-hyperglycemic agent, belongs to the class of thiazolidinediones, and is used for the treatment of diabetes mellitus type 2. In recent years, its anti-inflammatory activity has also been demonstrated in the literature for different diseases, including ocular inflammatory processes. Additionally, this drug belongs to Class II of the Biopharmaceutical Classification System, i.e., slightly soluble and highly permeable. The main objective of this study was to validate a new analytical HPLC-MS/MS method to quantify free-PGZ and PGZ from polymeric NPs to conduct nanoparticle application studies loaded with this active ingredient to transport it within ocular tissues. An accurate, sensitive, selective, reproducible and high throughput HPLC-MS/MS method was validated to quantify PGZ in cornea, sclera, lens, aqueous humor, and vitreous humor. The chromatographic separation was achieved in 10 min on a Kinetex C18 column. Linear response of PGZ was observed over the range of 5–100 ng/mL. The recovery of free-PGZ or PGZ from NPs was in the range of 85–110% in all tissues and levels tested. The intra-day and inter-day precision were <5% and <10%, respectively. The extracts were shown to be stable in various experimental conditions in all matrices studied. The range of concentrations covered by this validation is 80–1600 µg/kg of PGZ in ocular tissues. It is concluded that this method can be applied to quantify PGZ for in vivo and ex vivo biodistribution studies related to the ocular administration of free-PGZ and PGZ from nanoparticles.

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“…Previous studies have shown that PGZ was encapsulated into PLGA-PEG-NPs, suggesting its suitability as a pharmaceutical formulation that overcomes the poor solubility of PGZ in an aqueous phase [54] and targets specific tissues [46,55,56]. Moreover, this system showed good corneal and scleral permeation and sustained release, indicating these systems could be useful for drug delivery [52].…”

Section: Introductionmentioning

confidence: 99%

Stabilization by Nano Spray Dryer of Pioglitazone Polymeric Nanosystems: Development, In Vivo, Ex Vivo and Synchrotron Analysis

et al. 2021

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Pioglitazone-loaded PLGA-PEG nanoparticles (NPs) were stabilized by the spray drying technique as an alternative to the treatment of ocular inflammatory disorders. Pioglitazone-NPs were developed and characterized physiochemically. Interaction studies, biopharmaceutical behavior, ex vivo corneal and scleral permeation, and in vivo bioavailability evaluations were conducted. Fibrillar diameter and interfibrillar corneal spacing of collagen was analyzed by synchrotron X-ray scattering techniques and stability studies at 4 °C and was carried out before and after the spray drying process. NPs showed physicochemical characteristics suitable for ocular administration. The release was sustained up to 46 h after drying; ex vivo corneal and scleral permeation profiles of pioglitazone-NPs before and after drying demonstrated higher retention and permeation through cornea than sclera. These results were correlated with an in vivo bioavailability study. Small-angle X-ray scattering (SAXS) analysis did not show a significant difference in the organization of the corneal collagen after the treatment with pioglitazone-NPs before and after the drying process, regarding the negative control. The stabilization process by Nano Spray Dryer B-90 was shown to be useful in preserving the activity of pioglitazone inside the NPs, maintaining their physicochemical characteristics, in vivo bioavailability, and non-damage to corneal collagen function after SAXS analysis was observed.

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

Cited by 38 publications

References 63 publications

Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil

Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil

Development and Validation of an HPLC–MS/MS Method for Pioglitazone from Nanocarriers Quantitation in Ex Vivo and In Vivo Ocular Tissues

Stabilization by Nano Spray Dryer of Pioglitazone Polymeric Nanosystems: Development, In Vivo, Ex Vivo and Synchrotron Analysis

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