Design, optimization, and in vitro characterization of idebenone-loaded PLGA microspheres for LHON treatment

Rubén Varela-Fernández; Carlos Bendicho-Lavilla; Manuel Martin-Pastor; Rocío Herrero Vanrell; María Isabel Lema-Gesto; Miguel González-Barcia; Francisco Javier Otero-Espinar

doi:10.1016/j.ijpharm.2022.121504

Design, optimization, and in vitro characterization of idebenone-loaded PLGA microspheres for LHON treatment

Int J Pharm. 2022 Mar 25:616:121504. doi: 10.1016/j.ijpharm.2022.121504. Epub 2022 Feb 2.

Authors

Rubén Varela-Fernández¹, Carlos Bendicho-Lavilla², Manuel Martin-Pastor³, Rocío Herrero Vanrell⁴, María Isabel Lema-Gesto⁵, Miguel González-Barcia⁶, Francisco Javier Otero-Espinar⁷

Affiliations

¹ Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), Campus vida, Santiago de Compostela Zip Code: 15782, Spain; Clinical Neurosciences Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela Zip Code: 15706, Spain. Electronic address: rubenvf1@gmail.com.
² Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), Campus vida, Santiago de Compostela Zip Code: 15782, Spain; Institute of Materials iMATUS, University of Santiago de Compostela (USC), Campus vida, Santiago de Compostela, Zip Code: 15782, Spain; Paraquasil Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela, Zip Code: 15706, Spain. Electronic address: carlos.bendicho@gmail.com.
³ Magnetic Resonance Unit, Infrastructure Supporting Network of Research and Technological Development, University of Santiago de Compostela (USC), Campus vida, Santiago de Compostela Zip Code: 15782, Spain. Electronic address: manuel.martin@usc.es.
⁴ Innoftal Research Group (UCM 920415), Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University, Madrid Zip Code: 28040, Spain. Electronic address: rociohv@farm.ucm.es.
⁵ Clinical Neurosciences Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela Zip Code: 15706, Spain. Electronic address: mariaisabel.lema@usc.es.
⁶ Clinical Pharmacology Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela, Zip Code: 15706, Spain. Electronic address: miguel.gonzalez.barcia@sergas.es.
⁷ Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), Campus vida, Santiago de Compostela Zip Code: 15782, Spain; Institute of Materials iMATUS, University of Santiago de Compostela (USC), Campus vida, Santiago de Compostela, Zip Code: 15782, Spain; Paraquasil Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n Santiago de Compostela, Zip Code: 15706, Spain. Electronic address: francisco.otero@usc.es.

PMID: 35121045
DOI: 10.1016/j.ijpharm.2022.121504

Abstract

Biodegradable poly(lactic-co-glycolic acid) microspheres (PLGA MSs) are attractive delivery systems for site-specific maintained release of therapeutic active substances into the intravitreal chamber. The design, development, and characterization of idebenone-loaded PLGA microspheres by means of an oil-in-water emulsion/solvent evaporation method enabled the obtention of appropriate production yield, encapsulation efficiency and loading values. MSs revealed spherical shape, with a size range of 10-25 μm and a smooth and non-porous surface. Fourier-transform infrared spectroscopy (FTIR) spectra demonstrated no chemical interactions between idebenone and polymers. Solid-state nuclear magnetic resonance (NMR), X-ray diffractometry, differential scanning calorimetry (DSC) and thermogravimetry (TGA) analyses indicated that microencapsulation led to drug amorphization. In vitro release profiles were fitted to a biexponential kinetic profile. Idebenone-loaded PLGA MSs showed no cytotoxic effects in an organotypic tissue model. Results suggest that PLGA MSs could be an alternative intraocular system for long-term idebenone administration, showing potential therapeutic advantages as a new therapeutic approach to the Leber's Hereditary Optic Neuropathy (LHON) treatment by intravitreal administration.

Keywords: Controlled release; Idebenone; Intravitreal administration; LHON; Microencapsulation; Microparticles; Microspheres; PLGA.

MeSH terms

Humans
Microspheres
Optic Atrophy, Hereditary, Leber*
Particle Size
Polylactic Acid-Polyglycolic Acid Copolymer
Ubiquinone / analogs & derivatives

Substances

Ubiquinone
Polylactic Acid-Polyglycolic Acid Copolymer
idebenone