Pramipexole Dihydrochloride Loaded Mpegpcl Nanosuspension by Modified Nanoprecipitation: In Vitro and in Vivo Evaluation (original) (raw)
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Journal of Pharmacology and Experimental Therapeutics, 2005
Pramipexole has been shown to possess neuroprotective properties in vitro that are partly independent of its dopaminergic agonism. The site of neuroprotective action is still unknown. Using [ 3 H]pramipexole, we show that the drug enters and accumulates in cells and mitochondria. Detoxification of reactive oxygen species (ROS) by pramipexole is shown in vitro and in vivo by evaluating mitochondrial ROS release and aconitase-2 activity, respectively. Pramipexole and its (ϩ)-enantiomer SND919CL2X [low-affinity dopamine agonist; (ϩ)2-amino-4,5,6,7-tetrahydro-6-L-propylamino-benzathiazole dihydrochloride] possess equipotent efficacy toward hydrogen peroxide and nitric oxide generated in vitro and inhibit cell death in glutathione-depleted neuroblastoma cells. IC 50 values ranged from 15 to 1000 M, consistent with the reactivity of the respective radical and the compartmentalization of ROS generation and ROS detoxification. Finally, both compounds were tested in superoxide dismutase 1-G93A mice, a model of familial amyotrophic lateral sclerosis. SND919CL2X (100 mg/kg) prolongs survival time and preserves motor function in contrast to pramipexole (3 mg/kg), which shows an increase in running wheel activity before disease onset, presumably caused by the dopaminergic agonism. We conclude that both enantiomers, in addition to their dopaminergic activity, are able to confer neuroprotective effects by their ability to accumulate in brain, cells, and mitochondria where they detoxify ROS. However, a clinical use of pramipexole as a mitochondria-targeted antioxidant is unlikely, because the high doses needed for antioxidative action in vitro are not accessible in vivo due to dopaminergic side effects. In contrast, SND919CL2X may represent the prototype of a mitochondria-targeted neuroprotectant because it has the same antioxidative properties without causing adverse effects. Pramipexole (PPX) [(Ϫ)-2-amino-4,5,6,7-tetrahydro-6-Dpropylamino-benzathiazole] is a nonergot dopamine receptor agonist (subtypes D2 and D3) used for symptomatic treatment of Parkinson's disease. Preclinical studies show that nanomolar concentrations of PPX protect dopaminergic neurons in vitro (Ling et al., 1999) or in vivo (ϳ1 mg/kg) (Zou et
Nanotechnology-based drug delivery of ropinirole for Parkinson’s disease
Drug Delivery, 2017
A new drug delivery system is developed for ropinirole (RP) for the treatment of Parkinson's disease (PD) consisting of biodegradable poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). The formulation selected was prepared with 8 mg RP and 50 mg PLGA 502. This formulation exhibited mean encapsulation efficiency of 74.8 ± 8.2%, mean particle size lower than 155 nm, the zeta potential of À14.25 ± 0.43 mV and zero-order in vitro release of RP (14.13 ± 0.17 lg/h/10 mg NPs) for 5 d. Daily doses of the neurotoxin rotenone (2 mg/kg) given i.p. to male Wistar rats induced neuronal and behavioral changes similar to those of PD. Once neurodegeneration was established (15 d) animals received RP in saline (1 mg/kg/d for 35 d) or encapsulated within PLGA NPs (amount of NPs equivalent to 1 mg/kg/d RP every 3 d for 35 d). Brain histology and immunochemistry (Nissl-staining, glial fibrillary acidic protein and tyrosine hydroxylase immunohistochemistry) and behavioral testing (catalepsy, akinesia, rotarod and swim test) showed that RP-loaded PLGA NPs were able to revert PD-like symptoms of neurodegeneration in the animal model assayed.
Journal of Nanoscience and Nanotechnology, 2017
Parkinson's disease (PD) is characterized by the degeneration of the dopamine-producing cells in the substantia nigra. Early diagnosis and therapy is essential at the molecular level before initiation of symptomatic changes. Blood-brain barrier (BBB) penetration still remains a major challenge. Increased brain penetration and targeting can be achieved by formulating nanosized drug delivery systems using liposomes and niosomes. Other studies have been performed using pramipexole, but our study is novel in evaluating the penetration and antiparkinsonian effect of nanosized, polyethylene glycol (PEG)ylated pramipexole-encapsulated liposomes and niosomes. Nanosized, PEGylated, neutral and positively charged pramipexole-encapsulated liposomes and niosomes were formulated, characterized, and the release kinetics were evaluated. In vitro penetration of all formulations was evaluated using the BBB cell co-culture model. In vivo effectiveness of neutral, pramipexole-encapsulated liposomes and niosomes was evaluated in 6-hydroxydopamine (6-OHDA) lesioned rats by rotometer testing and autoradiography. All formulations exhibited approximately 10% encapsulation efficiency and around 100 nm particle sizes and fitted first-order release kinetics. All formulations were BBB permeable in vitro as determined by fluorescent images and fluorospectroscopy. Therefore, nanosized, neutral pramipexole-encapsulated niosomes showed better effects at a dosage approximately 9 times less than that administered using conventional pramipexole tablets for human in routine treatment. Nanosized PEGylated pramipexole liposomes and niosomes were blood brain barrier permeable. Nanosized pramipexole-encapsulated neutral niosomes showed potential therapeutic effects in a Parkinson's disease animal model depending on the nanosize and non-ionic surfactant properties of the niosomes. Further experiments are currently being performed to improve the therapeutic effects.
A Review on Nanoparticles for the Treatment in Parkinson's Disease
Parkinson's disease is the second most common progressive neurodegenerative disease that promotes neuronal cell death. The primary treatment strategy for Parkinson's disease involves the therapy of an MAO-B inhibitor molecule. Nanotechnology refers to the creation and utilization of materials whose constituents exist at the nanoscale; and, by convention, be up to 100 nm in size. Nanotechnology explores electrical, optical, and magnetic activity as well as structural behavior at the molecular and submolecular level. It has the potential to revolutionize a series of medical and biotechnology tools and procedures so that they are portable, cheaper, safer, and easier to administer. Nanoparticles show very high mechanical properties as well as many remarkable physical properties. Their reactivity, durability and different properties are additionally reliant upon their novel size, shape and construction; there is appropriate possibility for different business and homegrown applications, which incorporate catalysis, imaging, clinical applications, energybased examination, and ecological applications. Alzheimer's disease (AD) is a neurodegenerative disorder for which the research of new treatments is highly challenging. Since the fibrillogenesis of amyloid-β peptide 1-42 (Aβ1-42) peptide is considered as a major cause of neuronal degeneration, specific interest has been focused on aromatic molecules for targeting this peptide.
Recent advancements in ropinirole hydrochloride embedded nano-techniques in Parkinson’s treatment
ip innovative publication pvt. ltd , 2019
Abstract Parkinson's Disease (PD) is effecting 7-10 million people of worldwide as the report of WHO 2014. It has proved to be 2nd most a neuro-degenerative disorder of the central nervous system (CNS). It occurs due to the death of dopamine-generating cells in the substantia-nigra, a region of the midbrain. It is characterized by tremor, rigidity, bradykinesia, dementia, depression and falls or emerges with the progression of the disease. Ropinirole HCl is a low molecular weight, highly water soluble drug. It is rapidly absorbed from the G.I.T and mean peak plasma concentrations have been achieved within 1.5 h after oral doses. The oral bioavailability of Ropinirole HCl is 50% due to extensive first pass metabolism by the liver. Its mean plasma half-life is 5–6 h. The present study tries to enlighten the prior art related to Parkinson's treatment and to prepare Ropinirole HCl loaded Nano-structured lipid carriers (NLC) that may overcome the problem of bioavailability and bypass the blood brain barrier by preparing the intra-nasal drug delivery targeted to the brain thereby decreasing the dosing frequency and increasing patient compliance. Keywords: Parkinson's Disease, Bioavailability, NLC, Nano-technology.
Design and Characterization of Pramipexole
2021
The present investigation was undertaken to develop nnaoparticles ofa hydrophilic drug pramipexole dihydrochloride and improve the entrapment efficiency of the drug. Nanosuspension of pramipexole dihydrochloride was prepared with PLGA by the process of modified nanoprecipitation technique. The particle size, zeta potential, SEM, TEM and invitro dug release where performed. Nano-formulations are prepared with different concentrations of PLGA . The formulation variables such as polymer concentration were found to possess significant effect on the particle size and entrapment efficiency of drug in nanosuspension. The maximum entrapment efficiency, least particle size and optimal invitro drug release profile were exhibited with 1;2 ratio of drug and PLGA. The least particle size of 145 nm and maximum zeta potential value 34.8 mv were observed with PMPNP2 formulation. The SEM, TEM and invitro dug release of PMPNP2 were performed shows spherical shape with controlled release when compared...
Pramipexole Extended Release: A Novel Treatment Option in Parkinson's Disease
2010
Pramipexole, the most commonly prescribed dopamine agonist worldwide, meanwhile serves as a reference substance for evaluation of new drugs. Based on numerous clinical data and vast experiences, efficacy and safety profiles of this non-ergoline dopamine agonist are well characterized. Since October 2009, an extended-release formulation of pramipexole has been available for symptomatic treatment of Parkinson's disease. Pramipexole administration can be cut down from three times to once a day due to the newly developed extended-release formulation. This is considerable progress in regard to minimizing pill burden and enhancing compliance. Moreover, the 24 h continuous drug release of the once-daily extended-release formulation results in fewer fluctuations in plasma concentrations over time compared to immediate-release pramipexole, given three times daily. The present study summarizes pharmacokinetics and all essential pharmacological and clinical characteristics of the extendedrelease formulation. In addition, it provides all study data, available so far, with regard to transition and de-novo administration of extended-release formulation for patients with Parkinson's disease. It further compares efficacy and safety data of immediaterelease pramipexole with the extended-release formulation of pramipexole.
Brazilian Journal of Pharmaceutical Sciences, 2014
The objective of the research was to formulate and evaluate selegiline hydrochloride loaded chitosan nanoparticles for the Parkinson's therapy in order to improve its therapeutic effect and reducing dosing frequency. Taguchi method of design of experiments (L9 orthogonal array) was used to get optimized formulation. The selegiline hydrochloride loaded chitosan nanoparticles (SHPs) were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP) and tween 80 as surfactant. The SHPs had a mean size of (303.39 ± 2.01) nm, a zeta potential of +32.50mV, and entrapment efficiency of SHPs was 86.200 ± 1.38%. The in vitro drug release of SHPs was evaluated in phosphate buffer saline (pH 5.5) using goat nasal mucosa and found to be 82.529% ± 1.308 up to 28 h. Release kinetics studies showed that the release of drug from nanoparticles was anomalous (non-fickian) diffusion indicating the drug release is controlled by more than one process i.e. superposition of both phenomenon...
A review of pramipexole and its clinical utility in Parkinson’s disease
Expert Opinion on Pharmacotherapy, 2002
Parkinson's disease (PD) is a common neurodegenerative disorder characterised by selective loss of dopaminergic neurones in the substantia nigra and resulting in progressive disability. Therapy has focused on replacing depleted dopamine (DA) via supplementation with levodopa or DA agonists. Pramipexole (Mirapex ® , Pharmacia Corp.) has recently been approved for the treatment of PD. Evidence from preclinical studies and clinical trials have proven the effectiveness of this agent in ameliorating the symptoms of PD. There is also non-human evidence that pramipexole may be neuroprotective and could therefore possibly slow disease progression; however, this has yet to be proven in humans. The use of pramipexole may be limited by its side effect profile compared to standard therapies and its relatively higher cost compared to levodopa. Despite these concerns, pramipexole does have a role in the treatment of PD in all stages of the illness and may arguably be the treatment of choice in early disease. In addition to its use in PD, pramipexole has shown some utility in the treatment of restless legs syndrome (RLS), depression and schizophrenia.
The role of pramipexole in a severe Parkinson's disease model in mice
Therapeutic Advances in Neurological Disorders, 2010
Background: Pramipexole is one of a new generation of dopamine agonists. Recently there have been questions regarding its neuroprotective effects. These effects have been tested against various insults, which have yielded conflicting results. Methods: In this study, we introduced a combination of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/paraquat to induce a severe Parkinson's disease model. The mice, after receiving the combination of toxins, were evaluated using mortality rates and immunohistochemistry for degenerating tyrosine hydroxylase-positive neurons. Results and conclusions: Pramipexole was tested for its capacity to offer protection against neurotoxic the effects of MPTP/paraquat in this model; however, the results showed no improvement with pramipexole therapy.