Simultaneous co-delivery of neuroprotective drugs from multiloaded PLGA microspheres for the treatment of glaucoma
| Autor: | Li Guo, Rocío Herrero-Vanrell, Maria Francesca Cordeiro, Alicia Arranz-Romera, I.T. Molina-Martínez, Irene Bravo-Osuna, Ehtesham Shamsher, Nivedita Ravindran, Benjamin M. Davis, Sergio Esteban-Pérez |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Intraocular pressure Combination therapy genetic structures Ubiquinone Drug Compounding Pharmaceutical Science Ocular hypertension Glaucoma 02 engineering and technology Pharmacology Neuroprotection Dexamethasone Retina 03 medical and health sciences chemistry.chemical_compound Tecnología farmaceútica Polylactic Acid-Polyglycolic Acid Copolymer In vivo medicine Animals Humans 030304 developmental biology Melatonin 0303 health sciences Drug Carriers business.industry 021001 nanoscience & nanotechnology medicine.disease Farmacia Microspheres Transcription Factor Brn-3B eye diseases digestive system diseases Rats PLGA Disease Models Animal Drug Liberation Neuroprotective Agents Treatment Outcome chemistry Drug delivery Drug Therapy Combination Injections Intraocular 0210 nano-technology business |
| Zdroj: | E-Prints Complutense. Archivo Institucional de la UCM instname E-Prints Complutense: Archivo Institucional de la UCM Universidad Complutense de Madrid |
| Popis: | Glaucoma is a multifactorial neurodegenerative disorder and one of the leading causes of irreversible blindness globally and for which intraocular pressure is the only modifiable risk factor. Although neuroprotective therapies have been suggested to have therapeutic potential, drug delivery for the treatment of ocular disorders such as glaucoma remains an unmet clinical need, further complicated by poor patient compliance with topically applied treatments. In the present study we describe the development of multi-loaded PLGA-microspheres (MSs) incorporating three recognised neuroprotective agents (dexamethasone (DX), melatonin (MEL) and coenzyme Q10 (CoQ10)) in a single formulation (DMQ-MSs) to create a novel sustained-release intraocular drug delivery system (IODDS) for the treatment of glaucoma. MSs were spherical, with a mean particle size of 29.04 ± 1.89 μm rendering them suitable for intravitreal injection using conventional 25G–32G needles. >62% incorporation efficiency was achieved for the three drug cargo and MSs were able to co-deliver the encapsulated active compounds in a sustained manner over 30-days with low burst release. In vitro studies showed DMQ-MSs to be neuroprotective in a glutamate-induced cytotoxicity model (IC 50 10.00 ± 0.94 mM versus 6.89 ± 0.82 mM in absence of DMQ-MSs) in R28 cell line. In vivo efficacy studies were performed using a well-established rodent model of chronic ocular hypertension (OHT), comparing single intravitreal injections of microspheres of DMQ-MSs to their equivalent individual single-drug loaded MSs mixture (MSsmix), empty MSs, no-treatment OHT only and naive groups. Twenty one days after OHT induction, DMQ-MSs showed a significantly neuroprotective effect on RGCs compared to OHT only controls. No such protective effect was observed in empty MSs and single-drug MSs treated groups. This work suggests that multi-loaded PLGA MSs present a novel therapeutic approach in the management of retinal neurodegeneration conditions such as glaucoma. |
| Databáze: | OpenAIRE |
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