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

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Abstract

Purpose

The main goal of this study was to encapsulate Pioglitazone (PGZ), in biodegradable polymeric nanoparticles as a new strategy for the treatment of ocular inflammatory processes.

Methods

To improve their biopharmaceutical profile for the treatment of ocular inflammatory disorders, nanospheres (NSs) of PGZ were formulated by factorial design with poly (lactic-co-glycolic acid) polyethylene glycol (PLGA-PEG). Interactions drug-polymer have been carried out by spectroscopic (X-ray spectroscopy, FTIR) and thermal methods (DSC). The PGZ-NSs were tested for their in vitro release profile, cytotoxicity, and ocular tolerance (HET-CAM® test); ex vivo corneal permeation, and in vivo inflammatory prevention and bioavailability.

Results

The optimized system showed a negative surface charge of −13.9 mV, an average particle size (Zav) of around 160 nm, a polydispersity index (PI) below 0.1, and a high encapsulation efficiency (EE) of around 92%. According to the DSC results, the drug was incorporated into the NSs polymeric matrix. The drug release was sustained for up to 14 h. PGZ-NSs up to 10 μg/ml exhibited no retinoblastoma cell toxicity. The ex vivo corneal and scleral permeation profiles of PGZ-NSs showed that retention and permeation through the sclera were higher than through the cornea. Ocular tolerance in vitro and in vivo demonstrated the non-irritant character of the formulation.

Conclusion

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

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Abbreviations

DSC:

Differential Scanning Calorimetry

NSs:

Nanospheres

PEG:

Polyethylene glycol

PGZ:

Pioglitazone

PI:

Polydispersity index

PLGA:

Polylactic-co-glycolic acid

PPARγ:

Peroxisome proliferator-activated receptor

TEM:

Transmission electron microscopy

ZP:

Zeta potential

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ACKNOWLEDGMENTS AND DISCLOSURES

This work has benefited from the backing of the Spanish Ministry of Science and Innovation (MAT2014-59134R). The authors would like to acknowledge Lidia Gómez Segura for her help with the in vivo study. Ms. Marcelle Silva de Abreu acknowledges the positive contribution of the Coordination for the Improvement of Higher Education Personnel (CAPES) - Brazil for the PhD scholarship.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain

    Marcelle Silva-Abreu, Ana Cristina Calpena, Marta Espina, María Antonia Egea & María Luisa García

  2. Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Barcelona, Spain

    Marcelle Silva-Abreu, Ana Cristina Calpena, Marta Espina, María Antonia Egea & María Luisa García

  3. Department of Biology and Environment, School of Life and Environmental Sciences, (ECVA, UTAD), University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5001-801, Vila Real, Portugal

    Amelia M. Silva

  4. Centre for the Research and Technology of Agro-Environmental and Biological Sciences, University of Trás-os-Montes and Alto Douro CITAB-UTAD, 5001-801, Vila-Real, Portugal

    Amelia M. Silva

  5. Animal Facility, Bellvitge Health Sciences Campus, University of Barcelona, 08907, Barcelona, Spain

    Alvaro Gimeno

Authors
  1. Marcelle Silva-Abreu
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  2. Ana Cristina Calpena
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Correspondence to María Luisa García.

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Silva-Abreu, M., Calpena, A.C., Espina, M. et al. Optimization, Biopharmaceutical Profile and Therapeutic Efficacy of Pioglitazone-loaded PLGA-PEG Nanospheres as a Novel Strategy for Ocular Inflammatory Disorders. Pharm Res 35, 11 (2018). https://doi.org/10.1007/s11095-017-2319-8

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