Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres

Abstract The repair of infective bone defects is a great challenge in clinical work. It is of vital importance to develop a kind of bone scaffold with good osteogenic properties and long-term antibacterial activity for local anti-infection and bone regeneration. A porous mineralized collagen (MC) scaffold containing poly(d,l-lactide-co-glycolic acid) (PLGA) microspheres loaded with two antibacterial synthetic peptides, Pac-525 or KSL-W was developed and characterized via scanning electron microscopy (SEM), porosity measurement, swelling and mechanical tests. The results showed that the MC scaffold embedded with smooth and compact PLGA microspheres had a positive effect on cell growth and also had antibacterial properties. Through toxicity analysis, cell morphology and proliferation analysis and alkaline phosphatase evaluation, the antibacterial scaffolds showed excellent biocompatibility and osteogenic activity. The antibacterial property evaluated with Staphylococcus aureus and Escherichia coli suggested that the sustained release of Pac-525 or KSL-W from the scaffolds could inhibit the bacterial growth aforementioned in the long term. Our results suggest that the antimicrobial peptides-loaded MC bone scaffold has good antibacterial and osteogenic activities, thus providing a great promise for the treatment of infective bone defects.

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Evaluation of particulate systems supporting tumor cell fractions in a preventive vaccination against intracranial rat glioma

Journal of Neurosurgery ◽

10.3171/jns.2006.105.5.745 ◽

2006 ◽

Vol 105 (5) ◽

pp. 745-752 ◽

Cited By ~ 2

Author(s):

Anne Sapin ◽

Anne Clavreul ◽

Emmanuel Garcion ◽

Jean-Pierre Benoit ◽

Philippe Menei

Keyword(s):

Immune Response ◽

Plasma Membranes ◽

Plga Microspheres ◽

Term Survival ◽

Long Term Survival ◽

Rat Glioma ◽

Fischer 344 ◽

Cell Fractions ◽

Particulate Systems

Object Irradiated autologous tumor cells are commonly used as a source of antigens in antiglioma vaccinations to activate the immune system. As cell number is often a limiting factor in these cells’ preparation, the aim of the present study was to find a means that can lower the amount of cells required. Among strategies currently developed, adjuvant particulate systems offer a promising means to improve the antitumor immune response. In this study, the authors were interested in evaluating the role of particulate systems containing biodegradable microspheres that carry tumor cell fractions on their surfaces in the induction of a protective immunity in the 9L/Fischer 344 rat glioma model. The efficiency of these particulate systems was compared to that of irradiated 9L cells. Methods Particulate systems composed of poly(d,l-lactide-co-glycolide) (PLGA) microspheres that support 9L cell fractions on their surfaces (cell lysates or plasma membranes) or irradiated 9L cells alone were injected subcutaneously into the flanks of syngeneic Fischer 344 rats. Eighteen days later, the rats were intracranially injected with nonirradiated 9L cells. A study of survival in these animals and an analysis of the resulting immune response were then conducted. For the same amount of protein (50 μg) injected, irradiated 9L cells provided long-term survival in 30% of animals, whereas 9L plasma membranes adsorbed onto PLGA microspheres provided long-term survival in 10% of animals and cell lysates adsorbed onto microspheres provided long-term survival in 0%. Accordingly, particulate systems induced a lower T helper cell Type 1 (Th1) peripheral immune response than irradiated 9L cells. However, greater secretion of Th1 cytokines was observed when particulate systems were used than when cell fractions separated from microspheres were used, indicating the adjuvant property of these particulate systems. Conclusions Particulate systems have adjuvant properties but are still less efficient than irradiated whole tumor cells for vaccinations. Encapsulation of an activating molecule in the microsphere will be the next developmental step in the search for efficient antiglioma vaccinations.

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Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration

Pharmaceutics ◽

10.3390/pharmaceutics13020237 ◽

2021 ◽

Vol 13 (2) ◽

pp. 237

Author(s):

David Garcia-Herranz ◽

Maria Jesus Rodrigo ◽

Manuel Subias ◽

Teresa Martinez-Rincon ◽

Silvia Mendez-Martinez ◽

...

Keyword(s):

Animal Model ◽

Optic Nerve ◽

Ganglion Cells ◽

Histological Study ◽

Clinical Signs ◽

Plga Microspheres ◽

Chronic Glaucoma ◽

Progressive Degeneration ◽

Study Results

Progressive degeneration of neuroretinal tissue with maintained elevated intraocular pressure (IOP) to simulate chronic glaucoma was produced by intracameral injections of poly (lactic-co-glycolic) acid (PLGA) microspheres (Ms) in rat eyes. The right eye of 39 rats received different sizes of PLGA-Ms (2 µL suspension; 10% w/v): 14 with 38–20 µm Ms (Ms38/20 model) and 25 with 20–10 µm particles (Ms20/10 model). This novel glaucoma animal model was compared to the episcleral vein sclerosis (EPI) model (25 eyes). Injections were performed at baseline, two, four and six weeks. Clinical signs, IOP, retina and optic nerve thicknesses (using in vivo optical coherence tomography; OCT), and histological studies were performed. An IOP increment was observed in all three groups, however, the values obtained from the PLGA-Ms injection resulted lower with a better preservation of the ocular surface. In fact, the injection of Ms20/10 created a gentler, more progressive, and more sustained increase in IOP. This IOP alteration was correlated with a significant decrease in most OCT parameters and in histological ganglion-cell count for the three conditions throughout the eight-week follow-up. In all cases, progressive degeneration of the retina, retinal ganglion cells and optic nerve, simulating chronic glaucoma, was detected by OCT and corroborated by histological study. Results showed an alternative glaucoma model to the well-known episcleral vein model, which was simpler to perform, more reproducible and easier to monitor in vivo.

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