10 research outputs found
Simultaneous co-delivery of neuroprotective drugs from multiloaded PLGA microspheres for the treatment of glaucoma
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. Greater than 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 (IC50 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 naïve 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
Formulation of potential phytochemicals with neuroprotective action for the treatment of Alzheimer's disease, glaucoma and multiple sclerosis
PURPOSE: Neurodegenerative diseases such as Alzheimer’s disease (AD), glaucoma and multiple sclerosis (MS) are characterised by the death of neuronal cells. Resveratrol and curcumin are polyphenols with neuroprotective effects but a low bioavailability. My aim was to develop novel nanoparticle formulations of these polyphenols and, assess them in vitro and in vivo. METHODS: Resveratrol and curcumin were formulated independently into nanoparticles. These formulations were assessed for neuroprotection on rat retinal precursor cells (R28) used as an RGC model. Next, a triple transgenic AD (3xTg-AD) mouse model was treated with either resveratrol or curcumin nanoparticles (RNs or CNs) intranasally 5 days/week for 3 months. In the rat ocular hypertension (OHT) glaucoma model, RNs were given topically daily for 3 weeks. RNs were also given intranasally in a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE) daily for 1 month. After sacrifice, retinas were labelled with an RGC marker (Brn3a) in all models. In 3xTg-AD mice, brains were immunostained for amyloid-beta (Aβ) and phospho-tau (pTau). In the EAE model, optic nerves and spinal cords were stained to detect inflammation and demyelination. RESULTS: RNs and CNs had an encapsulation efficiency >70%. They were neuroprotective against glutamate excitotoxicity and hypoxia in vitro. They showed a reduction of Aβ and pTau deposition in the brain of 3xTg-AD mice but had no effect on RGC loss. In the OHT model, RNs reduced RGC loss after 3 weeks of treatment. Finally, RNs also reduced RGC loss in the EAE model after 1 month of treatment without any effect on the optic nerve and spinal cord inflammation and demyelination. CONCLUSIONS: Nanoparticle formulations increase resveratrol and curcumin solubility. They show neuroprotection in vitro and in vivo. They could be used as a paradigm shift in the treatment of neurodegenerative diseases. However, further experiments are necessary before clinical application
OD63: A comparative study of oral and intranasal resveratrol nanoparticle administration in a model of multiple sclerosis
Resveratrol Nanoparticles Are Neuroprotective in Experimental, Optic Neuritis (Slides)
Optic neuritis is the most common clinical manifestation of multiple sclerosis. Axonal damage and neuronal loss lead to permanent neurological disability in patients and its animal model, experimental autoimmune encephalomyelitis (EAE). Presently, treatments of this condition aim to reduce inflammation without showing any neuroprotection. Resveratrol is a natural polyphenol found in red wine with neuroprotective effects but poor solubility in water. Thus, a novel nanoparticle formulation of resveratrol was developed and assessed in a mouse model of EAE
Resveratrol Nanoparticles Are Neuroprotective in Experimental, Optic Neuritis (PDF)
Optic neuritis is the most common clinical manifestation of multiple sclerosis. Axonal damage and neuronal loss lead to permanent neurological disability in patients and its animal model, experimental autoimmune encephalomyelitis (EAE). Presently, treatments of this condition aim to reduce inflammation without showing any neuroprotection. Resveratrol is a natural polyphenol found in red wine with neuroprotective effects but poor solubility in water. Thus, a novel nanoparticle formulation of resveratrol was developed and assessed in a mouse model of EAE
Resveratrol Nanoparticles Are Neuroprotective in Experimental, Optic Neuritis (Video)
Optic neuritis is the most common clinical manifestation of multiple sclerosis. Axonal damage and neuronal loss lead to permanent neurological disability in patients and its animal model, experimental autoimmune encephalomyelitis (EAE). Presently, treatments of this condition aim to reduce inflammation without showing any neuroprotection. Resveratrol is a natural polyphenol found in red wine with neuroprotective effects but poor solubility in water. Thus, a novel nanoparticle formulation of resveratrol was developed and assessed in a mouse model of EAE
Nanoparticles Enhance Solubility and Neuroprotective Effects of Resveratrol in Demyelinating Disease
Resveratrol is a natural polyphenol which may be useful for treating neurodegenerative diseases such as multiple sclerosis (MS). To date, current immunomodulatory treatments for MS aim to reduce inflammation with limited effects on the neurodegenerative component of this disease. The purpose of the current study is to develop a novel nanoparticle formulation of resveratrol to increase its solubility, and to assess its ability to prevent optic nerve and spinal cord degeneration in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Resveratrol nanoparticles (RNs) were made using a thin rehydration technique. EAE mice received a daily oral administration of vehicle, RNs or unconjugated resveratrol for one month. They were assessed daily for clinical signs of paralysis and weekly for their visual acuity with optokinetic responses (OKR). After one month, their spinal cords and optic nerves were stained for inflammation and demyelination and retinal ganglion cells immunostained for Brn3a. RNs were stable for three months. The administration of RNs did not have any effect on clinical manifestation of EAE and did not preserve OKR scores but reduced the intensity of the disease. It did not reduce inflammation and demyelination in the spinal cord and the optic nerve. However, RNs were able to decrease RGC loss compared to the vehicle. Results demonstrate that resveratrol is neuroprotective by reducing RGC loss. Interestingly, neuroprotective effects and decreased disease severity occurred without reduction of inflammation or demyelination, suggesting this therapy may fill an unmet need to limit the neurodegenerative component of MS
Neuroprotection in glaucoma: old concepts, new ideas
Introduction: The disease process of glaucoma is thought to begin up to 20 years before a diagnosis can be made. While its current treatment paradigm seeks to reduce the rate of disease progression through reducing intraocular pressure, these interventions are of limited effectiveness and are typically made late. Together, this highlights an unmet clinical need for the development of novel techniques to facilitate the early diagnosis of glaucoma and the emergence of new treatment paradigms. This review provides a summary of recent developments in the early diagnosis and treatment of glaucoma, including updates on natural neuroprotective compounds. / Areas covered: A systematic review of the literature was conducted including the keywords retinal ganglion cell apoptosis, neuroprotection, resveratrol, curcumin, adaptive optics, and detection of apoptosing retinal cells. / Expert opinion: While a growing number of preclinical studies have reported the efficacy of neuroprotective interventions for the treatment of glaucoma, these technologies have not yet translated into clinical use. A likely explanation for this phenomenon is the relatively late stage at which glaucoma is currently diagnosed in patients. The development of techniques to diagnose glaucoma earlier in the disease process would enable the earlier administration of neuroprotective interventions which could slow glaucoma-associated vision loss