Co-delivery of glial cell–derived neurotrophic factor (GDNF) and tauroursodeoxycholic acid (TUDCA) from PLGA microspheres: potential combination therapy for retinal diseases

Arranz-Romera, Alicia; Esteban-Pérez, Sergio; Molina‐Martínez, Irene T.; Bravo‐Osuna, Irene; Herrero–Vanrell, R.

doi:10.1007/s13346-021-00930-9

Cited by 11 publications

(14 citation statements)

References 74 publications

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“… 52 The encapsulation efficacy was 58 ± 8%, which corresponds to a final loading of 0.41 μg of GDNF per mg of polymer. The results were similar to those obtained for other GDNF-loaded MPs and NPs, 53 , 54 but with the advantage of encapsulating GDNF under milder conditions. SEM analysis showed that GDNF-NPs were spherical in shape and confirmed that NP size distribution was uniform ( Figure 2 C).…”

Section: Resultssupporting

confidence: 85%

Encapsulation of MSCs and GDNF in an Injectable Nanoreinforced Supramolecular Hydrogel for Brain Tissue Engineering

et al. 2022

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The co-administration of glial cell line-derived neurotrophic factor (GDNF) and mesenchymal stem cells (MSCs) in hydrogels (HGs) has emerged as a powerful strategy to enhance the efficient integration of transplanted cells in Parkinson's disease (PD). This strategy could be improved by controlling the cellular microenvironment and biomolecule release and better mimicking the complex properties of the brain tissue. Here, we develop and characterize a drug delivery system for brain repair where MSCs and GDNF are included in a nanoparticle-modified supramolecular guest−host HA HG. In this system, the nanoparticles act as both carriers for the GDNF and active physical crosslinkers of the HG. The multifunctional HG is mechanically compatible with brain tissue and easily injectable. It also protects GDNF from degradation and achieves its controlled release over time. The cytocompatibility studies show that the developed biomaterial provides a friendly environment for MSCs and presents good compatibility with PC12 cells. Finally, using RNA-sequencing (RNA-seq), we investigated how the three-dimensional (3D) environment, provided by the nanostructured HG, impacted the encapsulated cells. The transcriptome analysis supports the beneficial effect of including MSCs in the nanoreinforced HG. An enhancement in the anti-inflammatory effect of MSCs was observed, as well as a differentiation of the MSCs toward a neuron-like cell type. In summary, the suitable strength, excellent selfhealing properties, good biocompatibility, and ability to boost MSC regenerative potential make this nanoreinforced HG a good candidate for drug and cell administration to the brain.

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Section: Resultssupporting

confidence: 85%

Encapsulation of MSCs and GDNF in an Injectable Nanoreinforced Supramolecular Hydrogel for Brain Tissue Engineering

et al. 2022

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“…Specifically, the quantity of BSA present in the microparticles largely exceeds that of GDNF, increasing the probability of interaction with the organic matrix in comparison to GDNF. This protective mechanism ensures the preservation of the growth factor biological activity throughout the experimental timeframe. ,, …”

Section: Discussionmentioning

confidence: 99%

“…This protective mechanism ensures the preservation of the growth factor biological activity throughout the experimental timeframe. 27,37,38 The entrapment efficiency ranged from 9 to 68%, and was heavily dependent on the nature of the encapsulated molecule, probably because of the different affinity between each active molecule and the inner organic phase of the emulsion used to produce the MPs. Different molecules were also associated with obvious morphological changes, as clearly shown in SEM micrographs.…”

Section: Discussionmentioning

confidence: 99%

“…26 Previous studies were mainly focused on the evaluation of GDNF loaded in MPs, along with the technological characterization of the in vitro and in vivo model devices. 27,28 The aim of this study was to assess the ocular safety profile of the produced MPs in vitro and in vivo. The devices were characterized for their technological features and their effects on human retinal pigment epithelial (ARPE-19) cells evaluated by the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) conversion assay and cytofluorometric assessment of apoptosis to verify the cell viability.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro and In Vivo Safety of Hyaluronic Acid-Decorated Microparticles for Intravitreal Injection of Palmitoylethanolamide, Citicoline, or Glial-Cell-Derived Neurotrophic Factor

et al. 2023

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The treatment of posterior eye segment diseases through intravitreal injection requires repeated injections of an active molecule, which may be associated with serious side effects and poor patient compliance. One brilliant strategy to overcome these issues is the use of drug-loaded microparticles for sustained release, aiming at reducing the frequency of injections. Therefore, the aim of this work was to assess the safety features of poly(lactic-co-glycolic acid) (PLGA)-based, hyaluronic acid-decorated microparticles loaded with palmitoylethanolamide (PEA), citicoline (CIT), or glial-cell-derived neurotrophic factor (GDNF). Microparticles were prepared by double emulsion–solvent evaporation and fully characterized for their technological features. Microparticles possessed a satisfactory safety profile in vitro on human retinal pigment epithelial (ARPE-19) cells. Interestingly, the administration of free GDNF led to a loss of cell viability, while GDNF sustained release displayed a positive effect in that regard. In vivo results confirmed the safety profile of both empty and loaded microparticles. Overall, the outcomes suggest that the produced microparticles are promising for improving the local administration of neuroprotective molecules. Further studies will be devoted to assess the therapeutic ability of microparticles.

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“…First, PLGA (400 mg) was dissolved in 0.7 mL of dichloromethane (DCM) by vortex mixing. Afterwards, a mixture of 40 mg DX and 40 mg MEL was ground in a mortar and added to the previous solution together with ethanol (25% v/v) [33]. The organic mixture was sonicated in an ice-water bath for 5 min and then agitated with a sonication probe for 1 min at 4 • C. A solution of 5 mL of aqueous polyvinyl alcohol (PVA) (2% w/v) was emulsified with the phase described above by using the homogenizer set at 6000 revolutions per minute (rpm) for 1 min.…”

Section: Elaboration Of Plga Microspheresmentioning

confidence: 99%

Validation of a Rapid and Easy-to-Apply Method to Simultaneously Quantify Co-Loaded Dexamethasone and Melatonin PLGA Microspheres by HPLC-UV: Encapsulation Efficiency and In Vitro Release

et al. 2022

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This paper discusses the development and validation of a rapid method for the reversed phase HPLC-UV quantification of biodegradable poly(D,L-lactic-co-glycolic) acid (PLGA) microspheres co-loaded with two neuroprotective agents (dexamethasone and melatonin) (DX-MEL-MSs) to be intravitreally administered as a promising glaucoma treatment. The study was performed to validate two procedures that quantify the content of the two active substances entrapped into the polymer matrix during an encapsulation efficiency assay and the amount of drugs liberated over time during the in vitro release assay. The reversed-phase method allowed for the simultaneous determination of dexamethasone and melatonin, which were respectively detected at 240.5 and 222.7 nm. Chromatographic separation was performed using an Ascentis® C18 HPLC Column (25 cm × 4.6 mm, 5 µm) with an isocratic mobile phase composed of methanol-water (70:30, v/v) with 1.0 mL min−1 flow rate. The two procedures were validated analytically in terms of system suitability testing, specificity, linearity, precision, accuracy, sensitivity, and robustness. Both the validated procedures were applied to characterize DX-MEL-MSs and were found appropriate to quantify the drug quantities encapsulated and estimate their release profile over 10 days. The validation study designed in this work can be helpful for planning any other protocols that refer to the quantification of PLGA based drug delivery systems.

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Co-delivery of glial cell–derived neurotrophic factor (GDNF) and tauroursodeoxycholic acid (TUDCA) from PLGA microspheres: potential combination therapy for retinal diseases

Cited by 11 publications

References 74 publications

Encapsulation of MSCs and GDNF in an Injectable Nanoreinforced Supramolecular Hydrogel for Brain Tissue Engineering

Encapsulation of MSCs and GDNF in an Injectable Nanoreinforced Supramolecular Hydrogel for Brain Tissue Engineering

In Vitro and In Vivo Safety of Hyaluronic Acid-Decorated Microparticles for Intravitreal Injection of Palmitoylethanolamide, Citicoline, or Glial-Cell-Derived Neurotrophic Factor

Validation of a Rapid and Easy-to-Apply Method to Simultaneously Quantify Co-Loaded Dexamethasone and Melatonin PLGA Microspheres by HPLC-UV: Encapsulation Efficiency and In Vitro Release

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