Delivery Of Dopamine Research Articles

Application of Nanocomposites and Nanoparticles in Treating Neurodegenerative Disorders.

Neurodegenerative diseases represent a formidable global health challenge, affecting millions and imposing substantial burdens on healthcare systems worldwide. Conditions, like Alzheimer's, Parkinson's, and Huntington's diseases, among others, share common characteristics, such as neuronal loss, misfolded protein aggregation, and nervous system dysfunction. One of the major obstacles in treating these diseases is the presence of the blood-brain barrier, limiting the delivery of therapeutic agents to the central nervous system. Nanotechnology offers promising solutions to overcome these challenges. In Alzheimer's disease, NPs loaded with various compounds have shown remarkable promise in preventing amyloid-beta (Aβ) aggregation and reducing neurotoxicity. Parkinson's disease benefits from improved dopamine delivery and neuroprotection. Huntington's disease poses its own set of challenges, but nanotechnology continues to offer innovative solutions. The promising developments in nanoparticle-based interventions for neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), have offered new avenues for effective treatment. Nanotechnology represents a promising frontier in biomedical research, offering tailored solutions to the complex challenges posed by neurodegenerative diseases. While much progress has been made, ongoing research is essential to optimize nanomaterial designs, improve targeting, and ensure biocompatibility and safety. Nanomaterials possess unique properties that make them excellent candidates for targeted drug delivery and neuroprotection. They can effectively bypass the blood-brain barrier, opening doors to precise drug delivery strategies. This review explores the extensive research on nanoparticles (NPs) and nanocomposites in diagnosing and treating neurodegenerative disorders. These nanomaterials exhibit exceptional abilities to target neurodegenerative processes and halt disease progression.

DNA tetrahedral nanocages as a promising nanocarrier for dopamine delivery in neurological disorders.

Dopamine is a neurotransmitter in the central nervous system that is essential for many bodily and mental processes, and a lack of it can cause Parkinson's disease. DNA tetrahedral (TD) nanocages are promising in bio-nanotechnology, especially as a nanocarrier. TD is highly programmable, biocompatible, and capable of cell differentiation and proliferation. It also has tissue and blood-brain barrier permeability, making it a powerful tool that could overcome potential barriers in treating neurological disorders. In this study, we used DNA TD as a carrier for dopamine to cells and zebrafish embryos. We investigated the mechanism of complexation between TD and dopamine hydrochloride using gel electrophoresis, fluorescence and circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), and molecular dynamic (MD) simulation tools. Further, we demonstrate that these dopamine-loaded DNA TD nanostructures enhanced cellular uptake and differentiation ability in SH-SY5Y neuroblastoma cells. Furthermore, we extended the study to zebrafish embryos as a model organism to examine survival and uptake. The research provides valuable insights into the complexation mechanism and cellular uptake of dopamine-loaded DNA tetrahedral nanostructures, paving the way for further advancements in nanomedicine for Parkinson's disease and other neurological disorders.

Enhanced Stability of Dopamine Delivery via Hydrogel with Integrated Graphene.

The synthesis of graphene-based materials for drug delivery represents an area of active research, and the use of graphene in drug delivery systems is promising due to its unique properties. Thus, in the present work, we discuss the potential of few-layer graphene in a hydrogel system for dopamine release. The hydrogels are frequently used for these systems for their special physico-chemical properties, which can ensure that the drug is effectively released in time. However, the release from such structures is mostly determined by diffusion alone, and to overcome this restriction, the hydrogel can be "improved" with nanoscale fillers like graphene. The release kinetics of the composite obtained were analyzed to better understand how the use of graphene, instead of the more common graphene oxide (GO) and reduced graphene oxide (rGO), affects the characteristics of the system. Thus, the systems developed in this study consist of three main components: biopolymer, graphene, and dopamine. The hydrogels with graphene were prepared by combining two different solutions, one with polyacrylic acid and agarose and one with graphene prepared by the exfoliation method with microwave irradiation. The drug delivery systems were developed by adding dopamine to the obtained hydrogels. After 24 h of release, the presence of dopamine was observed, demonstrating that the system developed can slow down the drug's degradation because of the interactions with the graphene nanoplates and the polymer matrix.

Reversal of pathological motor behavior in a model of Parkinson's disease by striatal dopamine uncaging.

Motor deficits observed in Parkinson's disease (PD) are caused by the loss of dopaminergic neurons and the subsequent dopamine depletion in different brain areas. The most common therapy to treat motor symptoms for patients with this disorder is the systemic intake of L-DOPA that increases dopamine levels in all the brain, making it difficult to discern the main locus of dopaminergic action in the alleviation of motor control. Caged compounds are molecules with the ability to release neuromodulators locally in temporary controlled conditions using light. In the present study, we measured the turning behavior of unilateral dopamine-depleted mice before and after dopamine uncaging. The optical delivery of dopamine in the striatum of lesioned mice produced contralateral turning behavior that resembled, to a lesser extent, the contralateral turning behavior evoked by a systemic injection of apomorphine. Contralateral turning behavior induced by dopamine uncaging was temporarily tied to the transient elevation of dopamine concentration and was reversed when dopamine decreased to pathological levels. Remarkably, contralateral turning behavior was tuned by changing the power and frequency of light stimulation, opening the possibility to modulate dopamine fluctuations using different light stimulation protocols. Moreover, striatal dopamine uncaging recapitulated the motor effects of a low concentration of systemic L-DOPA, but with better temporal control of dopamine levels. Finally, dopamine uncaging reduced the pathological synchronization of striatal neuronal ensembles that characterize unilateral dopamine-depleted mice. We conclude that optical delivery of dopamine in the striatum resembles the motor effects induced by systemic injection of dopaminergic agonists in unilateral dopamine-depleted mice. Future experiments using this approach could help to elucidate the role of dopamine in different brain nuclei in normal and pathological conditions.

Dopamine delivery systems based on C60 and C24 with B and N as substituents

Two different options as potential dopamine delivery systems were investigated in this study: fullerene C60- and C24-like structures. The systems being investigated include C60, C59X, C58X2, C24, C23X, and C22X2 (X represents B or N). Electron donor acceptor capacity and interaction energies were reported. Systems with one B are better electron acceptors than those with one N. The interaction of compounds containing B with dopamine is more favorable than the interaction of systems containing N. For a dopamine delivery system, at least two conditions are necessary. The first is the stability of the carrier-dopamine compound. This condition is fulfilled because C60-based heterofullerenes with B and dopamine form stable structures. Also, dopamine with C24-based structures containing B or N form stable structures. The second is that the interaction energy should be lower than the energy that binds dopamine to the receptor. Systems that fulfill the second condition include C60 and C58B2. The other systems present interaction energies that exceed 40 kcal/mol. Dopamine will bond to these systems and will most probably not be delivered at the receptor site, but these systems that interact strongly with dopamine may serve as agonists because they are good electron donors like dopamine. Systems with B could be antagonists of dopamine since they are good electron acceptors. This idea might be interesting to explore through experiments because heterofullerenes with B and dopamine might serve as antipsychotics rather than dopamine delivery systems.

The Periventricular Nucleus as a Brain Center Containing Dopaminergic Neurons and Neurons Expressing Individual Enzymes of Dopamine Synthesis

Since the 1980s, the concept of dopamine-rich brain centers as clusters of only dopaminergic neurons has been fundamentally revised. It has been shown that, in addition to dopaminergic neurons, most of these centers contain neurons expressing one of the enzymes of dopamine synthesis: tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC). We have obtained convincing evidence that in rats, the hypothalamic periventricular nucleus (PeVN) is one of the largest dopamine-rich centers, containing dopaminergic and monoenzymatic neurons. Indeed, using double immunostaining for TH and AADC, the PeVN was shown to contain almost three thousand dopaminergic and monoenzymatic neurons. According to high-performance liquid chromatography, PeVN contains L-DOPA and dopamine, which, apparently, are synthesized in monoenzymatic TH neurons and bienzymatic neurons, respectively. According to confocal microscopy, neurons (cell bodies, fibers), which were immunopositive only to TH, only to AADC, or both, are in close topographic relationships with each other and with the 3rd ventricle. These data suggest the mutual regulation of the neurons, as well as the delivery of dopamine and L-DOPA to the third ventricle, which is confirmed by their detection in the cerebrospinal fluid. Thus, evidence has been obtained that PeVN is one of the largest dopamine-rich centers of the brain, containing dopaminergic and monoenzymatic neurons.

Trifunctional fluorescent manganese ferrite nanoparticles for hyperthermia therapy, cell probing and drug delivery

Here we have reported a new protocol for drug delivery from hollow sphere manganese ferrite nanoparticles (HMF NPs). The crystalline structure of HMF NPs is obtained from XRD measurement and the morphological and elemental analysis are obtained from FESEM & TEM measurements. Here the HMF NPs are properly designed for delivery of dopamine (DA) as anticancer drug to cancer site. The DA polymerizes to a giant molecule polydopamine (PDA) inside hollow HMF in presence of TRIS buffer at pH (8.5) and a composite, HMF-PDA is formed. Being giant molecule polydopamine remain stable inside the hollow particles, but when these HMF-PDA come in contact of low pH i.e. pH 5 (cancer cells pH), free DA starts to be released. At hyperthermic temperature (45 °C) release enhances compare to physiological temperature (37 °C). The DA release studies are monitored by UV-visible absorption spectroscopy with progress of time at different temperatures and pH. It has been observed that HMF-PDA has fluorescent property whereas DA has no such effects. So, incorporation of PDA inside HMF and tagging of HMF-PDA with cancer cells can also be monitored by fluorescence imaging. Hence, we have successfully synthesized trifunctional HMF-PDA composite which can serve three purposes like cancer cell probing by fluorescence imaging, hyperthermia therapy and drug delivery by magnetic field and pH trigger method.

Studies on cancer cell death through delivery of dopamine as anti-cancer drug by a newly functionalized cobalt ferrite nano-carrier

Recently, a promising applicability of dopamine (DA) as an anticancer drug has been observed because it has an anti-angiogenesis property regulating tumour growth. We have proposed here a new approach for cancer therapy using cobalt-ferrite (CF) nanoparticles as a DA delivery agent by functionalizing CF with DA and polyethylene glycol (PEG). CF was synthesized by simple wet chemical method and its physical properties were investigated by X-ray diffraction (XRD) and Transmission Electron Microscopy (TEM) to confirm its structural and morphological properties respectively. After that DA was conjugated with CF (CF-DA) and then the CF-DA was polyethylene glycolated (CF-DA-PEG) for better fixing of DA on the CF and to deliver the dopamine very slowly into the cancer cells. FTIR study confirms the adsorption of DA and coating of PEG. We then carried on some experiments on cancer cells treating them with CF, DA, CF-DA, PEG and CF-DA-PEG to investigate and compare their anticancer properties. Detail mechanisms of cancer cell death were investigated by different techniques such as MTT assay, colony formation assay, anti migratory property, cell apoptosis, reactive oxygen species (ROS) generation, actin cytoskeleton disruption, western blot analysis, mitochondrial membrane disruption investigation etc. Our results convey an important message that CF-DA-PEG is able to deliver DA inside the A549 cells and also CF-DA-PEG shows an anti-cancer effect inducing apoptosis through activating the cyrochrome-c and caspase dependent apoptotic pathway and CF catalysed ROS generation.

Cyclodextrin-based nano-carrier for intelligent delivery of dopamine in a self-healable anti-corrosion coating

In the present work, the dopamine (DOP) performance was improved by encapsulation into a novel amphiphilic beta-cyclodextrin (β-CD) nano-carrier. The inclusion complexes (β-CD-DOP) structure was identified by Ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction analysis (XRD), Raman, and thermal gravimetric analysis (TGA) techniques. TGA assessments confirmed about 33% of DOP encapsulation in the β-CD cavity. The Electrochemical impedance spectroscopy (EIS) measurements in the solution (NaCl) phase after introducing β-CD-DOP have demonstrated 85% of corrosion attack retardation after 5 h iron exposure to 3.5% NaCl electrolyte. The samples were then analyzed via different morphological/elemental approaches, i.e., Field-Emission Scanning Electron Microscopy (FE-SEM), contact angle, Grazing incidence X-Ray diffraction (GIXRD), and Energy-dispersive X-ray spectroscopy (EDS)/Mapping. The self-healing mechanism after introducing β-CD-DOP into the SiC was investigated by EIS. Results confirmed the film resistance enhancement from 5540 Ω.cm2 to 10,900 Ω.cm2 after 1 h steel exposure, affirming a considerable self-healing degree after β-CD-DOP inclusion. The silane-based coating (SiC) defected zone morphology was studied by EDS/Mapping and FE-SEM techniques. Besides, notable resistance enhancement of the intact SiC has (from 13,032 Ω.cm2 to 16,231 Ω.cm2) demonstrated that most of the coating diffusion pathways were blocked by inclusion complexes, which could reduce the electrolyte/ion diffusion. Through Dispersion-corrected density functional theory (DFT-D) based explorations, the inclusion capacity of DOP inside the β-CD was investigated. The adsorption of DOP and β-CD/DOP on the steel substrate was proved by MC/MD calculations.

Potential Role of Proton Pump Inhibitors Against Human DRD2 Receptor in Drug Induced Hyperprolactinemia

Dopamine is a catecholamine neurotransmitter that control several important functions via different dopamine receptors(D1-D5). The Dopamine (DRD2) receptor and other D2 family receptors (D3 and D4) are predominantly involved in the inhibitory activities. One vital role of dopamine receptors is its involvement in the endocrine regulations including the hormone synthesis and their secretion. The regulation of prolactin hormone is mainly controlled through DRD2 receptors. Blocking the delivery of dopamine at these DRD2 receptors will cause an increase in serum prolactin levels. PPI�s are among the widely prescribed medications used for multiple gastric hypersecretory disorders and are shown to cause increase in serum prolactin level. This study focuses on computational methods to test PPIs interaction with dopamine D2 receptor through molecular docking & dynamics studies. The 3D structure of protein and the drugs were downloaded from PDB and PubChem databases. Protein and ligands were prepared followed by molecular docking. Complexes with best docking poses were then proceeded towards MD simulations of 60 ns. Results were then analyzed. This study confirmed that there is prospective affinity between proton pump inhibitors and dopamine D2 receptor, and dynamically stable complexes are formed after drug-receptor binding. MD simulations results confirmed the binding affinity between PPIs and Dopamine D2 receptor, concluding that the use of PPIs may be involved in drug induced hyperprolactinemia and other related effects.

Gene Therapy in the Management of Parkinson's Disease: Potential of GDNF as a Promising Therapeutic Strategy.

The limitations of conventional treatment therapies in Parkinson's disorder, a common neurodegenerative disorder, lead to the development of an alternative gene therapy approach. Multiple treatment options targeting dopaminergic neuronal regeneration, production of enzymes linked with dopamine synthesis, subthalamic nucleus neurons, regulation of astrocytes and microglial cells and potentiating neurotrophic factors, were established. Viral vector-based dopamine delivery, prodrug approaches, fetal ventral mesencephalon tissue transplantation and dopamine synthesizing enzyme encoding gene delivery are significant therapies evidently supported by numerous trials. The review primarily elaborates on the significant role of glial cell-line derived neurotrophic factor in alleviating motor symptoms and the loss of dopaminergic neurons in Parkinson's disease. Neuroprotective and neuroregenerative effects of GDNF were established via preclinical and clinical study outcomes. The binding of GDNF family ligands with associated receptors leads to the formation of a receptor-ligand complex activating Ret receptor of tyrosine kinase family, which is only expressed in dopaminergic neurons, playing an important role in Parkinson's disease, via its association with the essential protein encoded genes. Furthermore, the review establishes delivery aspects, like ventricular delivery of recombinant GDNF, intraparenchymal and intraputaminal delivery using infusion catheters. The review highlights problems and challenges of GDNF delivery, and essential measures to overcome them, like gene therapy combinations, optimization of delivery vectors, newer targeting devices, motor symptoms curbing focused ultrasound techniques, modifications in patient selection criteria and development of novel delivery strategies based on liposomes and encapsulated cells, to promote safe and effective delivery of neurotrophic factor and establishment of routine treatment therapy for patients.

Dopamine Delivery via pH-Sensitive Nanoparticles for Tumor Blood Vessel Normalization and an Improved Effect of Cancer Chemotherapeutic Drugs.

Tumor blood vessels have been reported to be abnormal in both structure and function compared with those in normal tissues, leading to a hostile microenvironment and inadequate antitumor drug delivery. Dopamine, a chemical messenger, is proven to inhibit angiogenesis and improve tumor vessel normalization. Here, a mesoporous silicon nanoparticle (MSN) is constructed that is responsive to the weakly acidic pH of the tumor extracellular matrix for steady delivery and tumor-localized release of dopamine. Then MSNs are functionalized with amine conjugated phenylboronicacid molecules, and dopamine is loaded by reacting with phenylboronic acid. In a weakly acidic environment, MSNs intelligently release dopamine due to the hydrolysis of boronic-ester bond between dopamine and phenylboronic acid, resulting in an evident inhibition of vascular endothelial cell migration and tubule formation. It is shown that loading of dopamine into the functional MSNs significantly prolong the circulatory half-life of this small molecule. After intravenous injection to tumor bearing mice, this nanoformulation induce tumor blood vessel normalization, thereby improving the antitumor chemotherapeutic efficacy of doxorubicin. This study demonstrates that the pH-responsive MSN offers great potential for delivery of dopamine in vivo and the normalization of tumor vessels by dopamine can provide an auxiliary treatment for cancer chemotherapeutic drugs.

Ionic Hydrogel for Accelerated Dopamine Delivery via Retrodialysis.

Local drug delivery directly to the source of a given pathology using retrodialysis is a promising approach to treating otherwise untreatable diseases. As the primary material component in retrodialysis, the semipermeable membrane represents a critical point for innovation. This work presents a new ionic hydrogel based on polyethylene glycol and acrylate with dopamine counterions. The ionic hydrogel membrane is shown to be a promising material for controlled diffusive delivery of dopamine. The ionic nature of the membrane accelerates uptake of cationic species compared to a nonionic membrane of otherwise similar composition. It is demonstrated that the increased uptake of cations can be exploited to confer an accelerated transport of cationic species between reservoirs as is desired in retrodialysis applications. This effect is shown to enable nearly 10-fold increases in drug delivery rates from low concentration solutions. The processability of the membrane is found to allow for integration with microfabricated devices which will in turn accelerate adaptation into both existing and emerging device modalities. It is anticipated that a similar materials design approach may be broadly applied to a variety of cationic and anionic compounds for drug delivery applications ranging from neurological disorders to cancer.

Levodopa/Benserazide PLGA Microsphere Prevents L-Dopa–Induced Dyskinesia via Lower β-Arrestin2 in 6-Hydroxydopamine Parkinson’s Rats

Prolonged pulsatile administration of Levodopa (L-dopa) can generate L-dopa–induced dyskinesia (LID). Numerous research has reported that continuous dopamine delivery (CDD) was useful in reducing the severity of LID. 6-OHDA lesioned rats were divided into two groups to receive intermittent L-dopa stimulation (L-dopa/benserazide) or Levodopa/benserazide PLGA microsphere (LBPM) for 3 weeks. rAAV (recombinant adeno-associated virus) vector was used to overexpress and ablation of β-arrestin2. We found that LBPM developed less AIM severity compared with standard L-dopa administration, whereas selective deletion of β-arrestin2 in striatum neurons dramatically enhanced the severity of dyskinesia by LBPM. On the contrary, the effects of LBPM in terms of ALO AIM were further relieved by β-arrestin2 overexpression. Furthermore, no significant change in motor behavior was seen either in inhibition or overexpression of β-arrestin2. In short, our experiments provided evidence that LBPM’s prevention of LID behavior was likely due to β-arrestin2, suggesting that a therapy modulating β-arrestin2 may offer a more efficient anti-dyskinetic method with a low risk of untoward effects.

SAT-476 A Case of Rathke's Cleft Cyst Presenting with Hyperprolactinemia

CASE: A 15 year-old G0P0 female with no significant PMH was referred to Endocrinology for oligomenorrhea and hyperprolactinemia. Menarche was at age 13 and she subsequently had oligomenorrhea for a year. She endorsed headaches and fatigue upon climbing a flight of stairs but denied vision changes, galactorrhea, hirsutism, SOB, and constipation. She was not on any psychotropic medications.The patient was hemodynamically stable with a normal physical examination including affect and cognition. Labs revealed prolactin-402 ng/mL (N=3-24 ng/mL), monomeric prolactin-277 ng/mL (macroprolactin=31%), cortisol-9.2 ug/dL one hour after cosyntropin, and DHEA-54.8 ug/dL (N=110-433.2ug/dL). TSH, LH, FSH, sex hormone binding globulin, testosterone, HCG, insulin-like growth factor, 17OH-progestereone were all within normal limits. MRI with and without contrast revealed a 1.5 x 1.8 x 1.8cm sellar lesion with characteristics most consistent with Rathke’s cleft cyst (RCC) with mass effect on the infundibulum and optic chiasm. The patient was started on cabergoline 0.25mg twice a week and Neurosurgery was consulted. Surgical resection was recommended. DISCUSSION: We present a rare case of symptomatic hyperprolactinemia in an adolescent female with radiologic evidence of RCC. RCC is an uncommon and usually asymptomatic intrasellar lesion, but pituitary dysfunction has been reported in 39% to 100% of these cases with prolactin levels generally less than 200 ng/mL. This hyperprolactinemia has been postulated to occur due to pituitary stalk compression from the sellar mass causing a decrease in dopamine (prolactin inhibitor) delivery. Possible explanations for RCCs with grossly elevated prolactin levels include: (1) coexisting pituitary adenoma, (2) cystic adenoma, and (3) pituitary stalk effect. (1) and (2) are the simplest explanations but radiologic features of adenomas were not seen on MRI. In our case, prolactin was higher than the typical levels seen in stalk compression raising concern for either coexisting pituitary adenoma or cystic adenoma although these are rare. This finding combined with hypocorticolism and radiologic evidence of mass effect warranted surgical intervention. CONCLUSION: Symptomatic RCC is rare, but clinicians should be aware that hyperprolactinemia is common in these cases. The degree of hyperprolactinemia may help guide decisions about further diagnostic evaluation and treatment. REFERENCES: 1. Eguchi K, Uozumi T, Arita K, et al. Pituitary function in patients with Rathke’s cleft cyst: significance of surgical management. Endocrine Journal. 1994; 41: 535-540. 2. Isono M, Kamida T, Kobayashi H, et al. Clinical features of symptomatic Rathke’s cleft cyst. Clin Neurol Neurosurg. 2001; 96-100. 3. Voelker JL, Campbell RL, Muller J. Clinical, radiographic, and pathological features of symptomatic Rathke’s cleft cyst. J Neurosurg. 1991; 74: 535-544.

The Logical Structure of Human Behavior

It is my contention that the table of intentionality (rationality, mind, thought, language, personality etc.) that features prominently here describes more or less accurately, or at least serves as an heuristic for, how we think and behave, and so it encompasses not merely philosophy and psychology, but everything else (history, literature, mathematics, politics etc.). Note especially that intentionality and rationality as I (along with Searle, Wittgenstein and others) view it, includes both conscious deliberative linguistic System 2 and unconscious automated prelinguistic System 1 actions or reflexes. I provide a critical survey of some of the major findings of two of the most eminent students of behavior of modern times, Ludwig Wittgenstein and John Searle, on the logical structure of intentionality (mind, language, behavior), taking as my starting point Wittgenstein’s fundamental discovery — that all truly ‘philosophical’ problems are the same — confusions about how to use language in a particular context, and so all solutions are the same — looking at how language can be used in the context at issue so that its truth conditions (Conditions of Satisfaction or COS) are clear. The basic problem is that one can say anything but one cannot mean (state clear COS for) any arbitrary utterance and meaning is only possible in a very specific context. I analyze various writings by and about them from the modern perspective of the two systems of thought (popularized as ‘thinking fast, thinking slow’), employing a new table of intentionality and new dual systems nomenclature. I show that this is a powerful heuristic for describing behavior. Thus, all behavior is intimately connected if one takes the correct viewpoint. The Phenomenological Illusion (oblivion to our automated System 1) is universal and extends not merely throughout philosophy but throughout life. I am sure that Chomsky, Obama, Zuckerberg and the Pope would be incredulous if told that they suffer from the same problem as Hegel, Husserl and Heidegger, (or that that they differ only in degree from drug and sex addicts in being motivated by stimulation of their frontal cortices by the delivery of dopamine (and over 100 other chemicals) via the ventral tegmentum and the nucleus accumbens), but it’s clearly true. While the phenomenologists only wasted a lot of people’s time, they are wasting the earth and their descendant’s future.

Combining Gene Transfer and Nonhuman Primates to Better Understand and Treat Parkinson's Disease.

Parkinson’s disease (PD) is a progressive CNS disorder that is primarily associated with impaired movement. PD develops over decades and is linked to the gradual loss of dopamine delivery to the striatum, via the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). While the administration of L-dopa and deep brain stimulation are potent therapies, their costs, side effects and gradual loss of efficacy underlines the need to develop other approaches. Unfortunately, the lack of pertinent animal models that reproduce DA neuron loss and behavior deficits—in a timeline that mimics PD progression—has hindered the identification of alternative therapies. A complementary approach to transgenic animals is the use of nonhuman primates (NHPs) combined with the overexpression of disease-related genes using viral vectors. This approach may induce phenotypes that are not influenced by developmental compensation mechanisms, and that take into account the personality of animals. In this review article, we discuss the combination of gene transfer and NHPs to develop “genetic” models of PD that are suitable for testing therapeutic approaches.

Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson’s disease

Efficient delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate borneol and lactoferrin co-modified nanoparticles (Lf-BNPs) encapsulated dopamine as a novel drug delivery system to achieve maximum therapeutic efficacy and reduce side effects for PD. Dopamine Lf-BNPs were prepared using the double emulsion solvent evaporation method and evaluated for physicochemical and pharmaceutical properties. In vitro cytotoxicity studies indicated that treatment with dopamine Lf-BNPs has relatively low cytotoxicity in SH-SY5Y and 16HBE cells. Qualitative and quantitative cellular uptake experiments indicated that Lf modification of NPs increased cellular uptake of SH-SY5Y cells and 16HBE cells, and borneol modification can promote the cellular uptake of 16HBE. In vivo pharmacokinetic studies indicated that AUC0–12 h in the rat brain for dopamine Lf-BNPs was significantly higher (p < .05) than that of dopamine nanoparticles. Intranasal administration of dopamine Lf-BNPs effectively alleviated the 6-hydroxydopamine-induced striatum lesion in rats as indicated by the contralateral rotation behavior test and results for striatal monoamine neurotransmitter content detection. Taken together, intranasal administration of dopamine Lf-BNPs may be an effective drug delivery system for Parkinson’s disease.

A MOF-based carrier for in situ dopamine delivery.

MIL-88A (Fe) MOF crystals were nucleated and grown around a polymer core containing superparamagnetic nanoparticles to assemble a new class of biocompatible particles for magnetophoretic drug delivery of dopamine. The carrier enabled efficient targeted release, dopamine protection from oxidative damage, long-term delivery and improved drug delivery cost-efficiency. After loading, dopamine was stable within the carrier and did not undergo oxidation. Drug release monitoring via spectrofluorimetry revealed a shorter burst effect and higher release efficiency than silica based carriers. The in vitro cytotoxicity at different MOF concentrations and sizes was assessed using PC12 cells as the neuronal cell model. The drug was directly uptaken into the PC12 cells avoiding possible side effects due to oxidation occurring in the extracellular environment.

Quantum Studies of Dopamine Delivery to Brain by Boron Nitride Nanotube Through Learning a New Language

Quantum Studies of Dopamine Delivery to Brain by Boron Nitride Nanotube Through Learning a New Language