Levodopa Drugs Research Articles

Lyotropic Liquid Crystalline Based Nasal Spray for Improved Parkinson's Treatment: Enhanced Superior Nasal Tract Deposition and Antioxidation Strategy

AbstractThe blood–brain barrier is one of the serious challenges in the treatment of Parkinson's disease (PD), which severely hinders the drug's brain bioavailability. In this study, a lyotropic liquid crystalline (LLC) based in situ gel nasal spray loaded with the first‐line drug Levodopa (LDA) for PD is developed to resolve this issue based on a nose‐to‐brain drug delivery approach. Specifically, the two key stages of LLC‐based in situ gel nasal spray, droplet deposition, and drug retention are tailored. By adjusting LLC's precursor solution's viscosity, the droplet deposition on the superior nasal tract can be increased by 18 times. Through nasal mucus‐triggered sol–gel transition, the LDA nasal cavity retention is prolonged by three times. The epigallocatechin gallate is incorporated into the LLC‐based in situ gel nasal spray to inhibit the autoxidation of LDA and alleviate the oxidative stress response in PD. The results show that the LLC‐based in situ gel nasal spray has a 26‐fold higher brain bioavailability of LDA compared to oral administration. The PD rats show a significant improvement in behavioral and cognitive disorders after administration. The LLC‐based in situ gel nasal spray is proved to work by reducing oxidative damage. This study is anticipated to offer a promising strategy for the clinical application of LDA.

From small to tall: breed-varied household pet dogs can be trained to detect Parkinson’s Disease

Parkinson’s Disease (PD) is a clinically diagnosed disease that carries a reported misdiagnosis rate of 10–20%. Recent scientific discoveries have provided evidence of volatile organic compounds in sebum that are unique to patients with PD. The primary objective of this study was to determine if companion dogs could be trained to distinguish between sebum samples provided by PD-positive patients and PD-negative human controls. This was a randomized, handler-blind, controlled study. Twenty-three canines of varying breeds, ages, and environmental backgrounds were included. The study period encompassed 200 total working days from 2021 to 2022. Factors investigated included donor gender and levodopa drug affectivity, as well as canine breed, age, and duration of training time. The findings in this study were compiled from data collected during the final two years of a seven-year research program. For this two-year reporting period, when averaged as a group, the 23 dogs were 89% sensitive and 87% specific to olfactory distinction between PD-positive and PD-negative human donor samples. Ten of the twenty-three dogs averaged 90% or higher in both sensitivity and specificity. In 161 separate trials, a dog was presented with both novel PD-positive and PD-negative samples. For these novel exposures, the dogs collectively averaged 86% sensitivity and 89% specificity. PD medication was also investigated and was found to have no discernible impact on canine sensitivity or specificity results. Study findings support the application of companion dogs, trained with force-free, reward-based methodologies, for the detection of PD-positive and PD-negative samples under controlled conditions.

A REVIEW ON PARKINSONISM: AYURVEDA PERSPECTIVE

Parkinsonism is a clinical syndrome that consists of four cardinal signs: Tremor, Rigidity, Akinesia and Postural disturbances (TRAP). It is also called as the Shaking Palsy or Paralysis agitans. Parkinson’s disease is a common cause of the TRAP syndrome, but there are numerous other causes which can be considered as the differential diagnosis. Parkinson’s disease specifically refers to patients who have Parkinsonism, without any atypical features and who have essentially normal MRI that excludes other causes for their Parkinsonian symptoms. The main difference between the two is the effect of levodopa drug in Parkinson’s disease and not the other.

The effect of the Pisa syndrome on balance and gait in Parkinson’s disease: a comparative study

INTRODUCTION. Pisa syndrome is a postural deformity that can lead to impaired posture control and balance in patients with Parkinson’s disease (PD), which increases the risk of injury and reduces the quality of life. AIM. To study the effect of the Pisa syndrome on postural control, balance and gait of patients with Parkinson’s disease. HYPOTHESIS. It is assumed that patients with PD with the Pisa syndrome will have specific features of postural control and balance, which must be taken into account when developing rehabilitation technologies for correcting postural disorders. MATERIALS AND METHODS. As part of the comparative study, 30 people of both sexes were examined, all study participants received levodopa drugs in an individual dosage selected by a neurologist-parkinsonologist. The subjects were divided into 2 groups of 15 people each according to the principle of the presence of the Pisa syndrome and its absence. Criteria for inclusion in the groups: voluntary informed consent of persons with PD for the study; age from 45–80 years, stage 2–4 of Hoehn-Yahr Parkinson’s disease, absence of other diseases and gross cognitive impairment. The diagnosis was carried out using the COBS Physiomed stabilometry system and the EQ-5D-3L questionnaire, a diary of falls and a dynamic gait index (DGI). The reliability of the differences was determined by the Mann-Whitney U-test. Data processing was carried out using the Statistica 10 program. RESULTS. Significant differences were revealed in the parameter of the coordination index of the Standing Balance test for the right leg and on the EQ-5D-3L scale at a significance level of p 0.05, in the group of people with PD without the Pisa syndrome, the quality of life was significantly higher, the number of falls was significantly higher in the group of people suffering from PD with the Pisa syndrome towers. DISCUSSION. Walking with a change of direction and multitasking is the most significant problem for people with PD with the Pisa syndrome, the differences between the groups are significant at a significance level of p 0.01. CONCLUSION. Patients with PD and Pisa syndrome have altered gait associated with body tilt forward, instability and decreased balance control.

Icariin attenuates dopaminergic neural loss in haloperidol-induced Parkinsonism in rats via GSK-3β and tyrosine hydroxylase regulation mechanism

Parkinson’s Disease (PD) is an age-dependent, incessant, dynamic neurodegenerative illness. In animal models, the administration of the dopaminergic D2 antagonist Haloperidol (HP) affects the nigrostriatal pathway, inducing catalepsy, a state of immobility like PD, bradykinesia, and akinesia. The present study investigated the neural effects of Icariin (ICA), a flavonoid derived from Herba Epimedii, against HP-induced PD in rats compared to a standard drug levodopa (L-DOPA). Twenty-four adult male rats were divided into 4 groups: the control group treated with vehicle, the 2nd group treated with HP intraperitoneally, the 3rd group treated with the same dose of HP+L-DOPA orally, and the 4th one, treated with the same dose of HP+ICA orally. All the groups were treated for fourteen consecutive days. Two days before the last dose, locomotor activity was assessed in open field and rotarod tasks. At the end of the experiment, the malondialdehyde, nitric oxide (NO), iron, glycogen synthase kinase-3beta (GSK-3β), and tyrosine hydroxylase (TH) contents, glutathione S-transferase, catalase, superoxide dismutase, activities were estimated in the midbrain. Also, cortex and midbrain monoamine contents (norepinephrine, dopamine, and serotonin) were determined. Moreover, the midbrain histopathology was detected in all treated groups. The results suggested that the neuroleptic effect of HP was completely improved by ICA. This improvement occurred by decreasing the neurotoxicity via lowering midbrain lipid peroxidation, NO, GSK-3β contents, increasing antioxidant biomarkers, TH, and recovering the treated groups' cortex and midbrain monoamines contents. In conclusion, this study suggests that ICA is a suitable treatment for Parkinson's induced by HP.

Computational quantum mechanical investigation of the functionalized AlN nanotube as the smart carriers for levodopa drug delivery: a DFT analysis

Computational quantum mechanical investigation of the functionalized AlN nanotube as the smart carriers for levodopa drug delivery: a DFT analysis

Impaired cognitive and motor function are coincident with l-DOPA-induced dyskinesia in a model of Parkinson’s disease

Dopamine transmission has been implicated in motor and cognitive function. In Parkinson’s disease (PD), dopamine replacement using the precursor drug l-DOPA is the predominant treatment approach, but long-term exposure leads to the onset of dyskinesias (LIDs). Chronic l-DOPA exposure has been associated with changes in gene expression and altered cortico-striatal plasticity. The aim of this research was to assess the functional consequence of long-term l-DOPA exposure on cognitive and motor function using a rodent model of PD. Across two independent experiments, we assessed the impact of chronic l-DOPA exposure, or a control D2R agonist, on motor and cognitive function in intact and in hemi parkinsonian rats, in the absence of drug. Abnormal involuntary movements associated with LID were measured and brain tissues were subsequently harvested for immunohistochemical analysis. Exposure to chronic l-DOPA, but not the D2R agonist, impaired motor and cognitive function, when animals were tested in the absence of drug. A meta-analysis of the two experiments allowed further dissociation of l-DOPA -treated rats into those that developed LIDs (dyskinetic) and those that did not develop LIDs (non-dyskinetic). This analysis revealed impaired cognitive and motor performance were evident only in dyskinetic, but not in non-dyskinetic, rats. These data reveal a functional consequence of the altered plasticity associated with LID onset and have implications for understanding symptom progression in the clinic.

Analytical assessment of a novel RP-HPLC method for the concurrent quantification of selected pharmaceutical drugs levodopa and carbidopa using eight greenness metrics comparing to the lean six sigma approach

BackgroundIntegrating green chemistry principles into analytical processes is vital for sustainability and accuracy. AimThis study is dedicated to finding eco-friendly solutions that replace harmful substances and reduce waste production. The suggested work examined eight tools for assessing the greenness and sustainability of a newly validated RP-HPLC technique that quantitatively determines levodopa (LEV) and carbidopa (CAR) drugs in their bulk and pharmaceutical formulations. We also incorporated the lean six sigma methodology to ensure accuracy and efficiency. MethodThe optimal liquid chromatographic conditions (HPLC) for achieving the highest resolution and results in our method are as follows: employing a mobile phase composition consisting of a mixture of phosphate buffer pH 2.2 and ethanol (90:10 v/v) at a flow rate of 1 mL/min, using a C18 column (150 mm × 4.6 mm) and employing an isocratic mode of elution at a wavelength of 280 nm. ResultsThe calibration curves were established for LEV and CAR in the 3–50 μg/mL range to study the linearity with coefficients of determination (R2 ∼0.999). The study determined that the limits of detection (LOD) and quantification (LOQ) for LEV were 1.95 μg/mL and 5.93 μg/mL, respectively. Meanwhile, the results for CAR were 0.67 μg/mL and 2.04 μg/mL for LOD and LOQ, respectively. The developed method has demonstrated accuracy and validity in the simultaneous determination and quantification of LEV and CAR, with a relative standard deviation (RSD) of less than 2%. The method's accuracy was confirmed through recovery studies, demonstrating significant results within the acceptable range of 98–102%. Specifically, the recovery test values for LEV and CAR were 99.75% and 98.97%, respectively. ConclusionThe specificity and selectivity of the developed method have been revealed through forced degradation studies conducted through The International Council for Harmonization (ICH) criteria. The technique could determine and quantify the two drugs even in the presence of their degradants. Our proposed approach beats the previous HPLC methods in adherence to green chemistry principles, providing reliable and precise outcomes with better qualitative and quantitative metrics. It's the most effective and eco-friendly solution for chemical analysis.

Unravelling the Molecular Mechanisms of a Quercetin Nanocrystal for Treating Potential Parkinson's Disease in a Rotenone Model: Supporting Evidence of Network Pharmacology and In Silico Data Analysis.

The prevalence of Parkinson's disease places a significant burden on society; therefore, there is an urgent need to develop more effective drugs. However, the development of these drugs is both expensive and risky. Quercetin (QUE) has potent pharmacological effects on neurodegenerative diseases, but its low solubility in water and poor bioavailability limit its use in pharmaceutical applications. In this study, Quercetin nanocrystals (QNC) were synthesized and compared to standard QUE. A network-pharmacology-based methodology was applied, including target prediction, network construction, a gene ontology (GO) analysis, a KEGG pathway enrichment analysis, and molecular docking. This study aimed to identify the targets of QUE relevant to the treatment of Parkinson's disease and investigate the associated pharmacological mechanisms. Most of the predicted targets are involved in dopamine uptake during synaptic transmission. QUE regulates the key targets DRD2 and DRD4, which significantly affect dopaminergic synapses. The molecular docking results showed that QUE had a better binding affinity than the standard drug l-Dopa. From these experiments, it can be concluded that QNC effectively reduced the adverse effects caused by rotenone-induced oxidative stress in biochemical, neurochemical, and histopathological alterations. Therefore, QNC can potentially treat Parkinson's disease, and its effectiveness should be assessed in future clinical trials.

A Study to Evaluate the Neuroprotective property of Aqueous Extract of Mentha piperita Leaves on Haloperidol Induced Parkinsonism in Experimental rats

The main objective of the proposed study was designed to investigate the neuroprotective property of aqueous extract of the Mentha piperita leaves (AEMPL) against haloperidol induced Parkinsonism in experimental animals. Rats were divided into 5 groups (n=6 animals). Group 1 received vehicle control, Group 2 received Haloperidol (1mg/kg, i.p.), Group 3receivedstandard drug Sinemet (125mg/kg p.o.), Group4andGroup5treated with lower (100mg/kg, p.o.) and higher (250mg/kg, p.o.) doses of AEMPL respectively for 14 days. Later motor co-ordination (rota-rod), locomotor activity (actophotometer) and catalepsy bar test was performed and also brain histopathological examination was also done. Both the lower and higher doses of aqueous extract of Mentha piperita leaves showed dose dependent, extremely significant increases in locomotor activity by increasing number of cuts, decreases fall off time and also decreases in latency period in metal bar test, histopathological examination shows reduction in neuronal loss and normal brain architecture was observed when compared haloperidol treated group. Hence Mentha piperita shows neuroprotective activity because of potential anti-oxidant property. The obtained result was comparable with that of the standard drug levodopa+carbidopa (Sinemet). The outcome of the present study provides the evidence that the aqueous extract of Mentha piperita leaves reported that it has dose dependent beneficial neuroprotective effect against haloperidol induced Parkinson’s disease in experimental rats.

Torsion dystonia type 30. Clinical observation. Case report

A 58-year-old patient with type 30 dystonia (OMIM619291) detected by genome-wide sequencing was described. A variant of rs778751388, not previously described in the literature, has been identified in the heterozygous state in exon 2 of 24 of the VPS16 gene, leading to the amino acid substitution of P.Cys36A4rg. DNA change (HG38)(protein change) 20:g.2859771TC ENST00000380445.8:c.106TC ENSP00000369810.3:p.Cys36Arg. The patient's disease began quite late, in the 4th decade of life, with spastic torticollis. Subsequently, the spread of the pathological process involving the muscles of the neck, the right upper limb, then the right lower limb, myoclonia of the right hand and tremor of the right lower limb was noted. Secondary mitochondrial disorders were revealed in the form of an increase in the level of lactate in the blood before and after loading with carbohydrates. A decrease in the activity of mitochondrial enzymes in peripheral blood lymphocytes was also revealed: succinate dehydrogenase, an enzyme of the mitochondrial respiratory chain complex II; -glycerophosphate dehydrogenase involved in mitochondrial fat metabolism; glutamate dehydrogenase (amino acid metabolism in mitochondria). The level of lactate dehydrogenase in peripheral blood lymphocytes in the patient was elevated. The identified secondary mitochondrial disorders may be an indication for the appointment of energotropic medicines along with levodopa drugs and dopaminergic receptor agonists. In the presented observation, it can be argued about autosomal dominant inheritance, since the patient has a characteristic clinical picture of the disease and a mutation in the heterozygous state in the VPS16 gene was detected.

Synthesis, in silico Studies and Pharmacological Evaluation of a New Series of Indanone Derivatives as Anti-Parkinsonian and Anti-Alzheimer's Agents.

Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common forms of neurodegenerative disorders. The aim of the current work is to study the potential of some new indanone derivatives for the treatment of these neurological disorders. A new series of 4-(2-oxo-2-aminoethoxy)-2-benzylidene substituted indanone derivatives have been synthesized and studied for anti-Parkinsonian and anti-Alzheimer's effects. Substitution of different aminoalkyl functionalities at the para position of 2-benzylidene moiety of indanone ring resulted in the formation of potent anti-parkinsonian and anti-Alzheimer's agents (5-10). The neuroprotective effects of newly synthesized compounds were evaluated using perphenazine (PPZ)-induced catatonia in rats and LPS-induced cognitive deficits in mice models. Further, in silico molecular modelling studies of the new indanone derivatives were performed by docking against the 3D structures of various neuroinflammatory mediators, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and monoamine oxidase-B (MAO-B), to gain the mechanistic insights of their anti-Alzheimer's and antiparkinsonian effects. The newly synthesized indanone analogues 5-10 were found effective against PPZinduced motor dysfunction and LPS-induced memory impairment in animal models. Among all the synthesized analogues, morpholine-substituted indanone 9 displayed maximum anti-parkinsonian activity, even better than the standard drug L-DOPA, while pyrrolidine and piperidine substituted analogues 5 and 6 were found to be the most potent anti-Alzheimer's agents. The new 2-arylidene-1-indanone analogues show good potential as promising leads for designing compounds against Parkinson's and Alzheimer's diseases.

Curcumin modulation of L-dopa and rasagiline-induced neuroprotection in rotenone model of Parkinson's disease.

Parkinson's disease (PD) is one of the most incurable, chronic, and progressive neurodegenerative disorders Worldwide. Curcumin, a natural polyphenolic anti-oxidant compound, has a long history in traditional medicine. We investigate the effect of curcumin on brain oxidative stress, DNA fragmentation, and motor changes in rotenone-induced PD in mice. The possible modulation of the anti-parkinsonian action of drugs L-dopa and rasagiline by curcumin was also studied. Mice received rotenone 1.5 mg/kg and were treated with curcumin (150 mg/kg), L-dopa (25 mg/kg), rasagiline (1 mg/kg), L-dopa+curcumin, or rasagiline+curcumin. Striatal malondialdehyde, reduced glutathione, nitric oxide, tyrosine hydroxylase, and brain DNA fragmentations were measured. Histopathological examination of brain tissues was done. Motor coordination and behavioral tests such as wire-hanging, stair, and wood-waking tests were included. Rotenone caused elevation in brain malondialdehyde and nitric oxide contents, depletion of reduced glutathione accompanied by a reduction in rearing behavior, and impairment of motor activity in wire-hanging, stair, and wood-waking tests. Also, severe DNA fragmentation in the striatum, marked decrease of substantia nigra pigmented neurons, neuronal degeneration in the cerebral cortex and hippocampus, decreased glial fibrillary acidic protein reaction (GFAP) and glial cell size in the cerebral cortex were caused by rotenone. In rotenone-treated mice, brain oxidative stress was decreased by curcumin, L-dopa, rasagiline, curcumin+L-dopa, and curcumin+rasagiline. These treatments also prevented DNA fragmentation and markedly improved the motor and behavioral impairment caused by rotenone. Rotenone-induced histopathological changes were ameliorated by curcumin which had an additive effect to that of l-dopa or rasagiline. These data indicate that curcumin showed additive neuroprotective effects to L-dopa or rasagiline and ameliorated neurodegeneration, DNA fragmentation, and motor defects caused by rotenone in mice.

Improvement of the results of the therapy of Parkinson’s disease with the use of the drug levodopa of prolonged action

Improvement of the results of the therapy of Parkinson’s disease with the use of the drug levodopa of prolonged action

Motion sickness susceptibility and visually induced motion sickness as diagnostic signs in Parkinson's disease.

Postural instability and loss of vestibular and somatosensory acuity can be part of the signs encountered in Parkinson's Disease (PD). Visual dependency is described in PD. These modifications of sensory input hierarchy are predictors of motion sickness (MS). The aim of this study was to assess MS susceptibility and effects of real induced MS in posture. 63 PD patients, whose medication levels (levodopa) reflected the pathology were evaluated, and 27 healthy controls, filled a MS questionnaire; 9 PD patients and 43 healthy controls were assessed by posturography using virtual reality. Drug amount predicted visual MS (p=0.01), but not real induced MS susceptibility. PD patients did not experience postural instability in virtual reality, contrary to healthy controls. Since PD patients do not seem to feel vestibular stimulated MS, they may not rely on vestibular and somatosensory inputs during the stimulation. However, they feel visually induced MS more with increased levodopa drug effect. Levodopa amount can increase visual dependency. The strongest MS predictors must be studied in PD to better understand the effect of visual stimulation and its absence in vestibular stimulation.

Describing inhibitor specificity for the amino acid transporter LAT1 from metainference simulations

The human L-type amino acid transporter 1 (LAT1; SLC7A5) is a membrane transporter of amino acids, thyroid hormones, and drugs such as the Parkinson’s disease drug levodopa (L-Dopa). LAT1 is found in the blood-brain barrier, testis, bone marrow, and placenta, and its dysregulation has been associated with various neurological diseases, such as autism and epilepsy, as well as cancer. In this study, we combine metainference molecular dynamics simulations, molecular docking, and experimental testing, to characterize LAT1-inhibitor interactions. We first conducted a series of molecular docking experiments to identify the most relevant interactions between LAT1’s substrate-binding site and ligands, including both inhibitors and substrates. We then performed metainference molecular dynamics simulations using cryoelectron microscopy structures in different conformations of LAT1 with the electron density map as a spatial restraint, to explore the inherent heterogeneity in the structures. We analyzed the LAT1 substrate-binding site to map important LAT1-ligand interactions as well as newly described druggable pockets. Finally, this analysis guided the discovery of previously unknown LAT1 ligands using virtual screening and cellular uptake experiments. Our results improve our understanding of LAT1-inhibitor recognition, providing a framework for rational design of future lead compounds targeting this key drug target.

PECULIARITIES OF MOTOR FLUCTUATIONS AT DIFFERENT FORMS OF PARKINSON'S DISEASE

Levodopa is known as one of the most effective drugs for the treatment of Parkinson's disease. Unfortunately, there is no levodopa, which does not have side effects on the body under the long-term use. After several years of receiving this therapy, the response to this medicine changes in most patients: the duration of the single dose action decreases, sharp fluctuations in the patient's condition (motor fluctuations) and dyskinesia appear. The purpose of our study is to investigate the frequency and nature of motor fluctuations in various forms of Parkinson's disease and to evaluate their impact on the quality of life of patients. We examined 80 patients with Parkinson's disease who were undergoing inpatient treatment at the neurological department of the Sklifosovsky Poltava Regional Clinical Hospital and the Center for patients with Parkinson's disease and other neurodegenerative diseases at the Department of Nervous Diseases, Poltava State Medical University. Age, length of the disease, length of levodopa therapy and levodopa dosage, frequency and nature of motor fluctuations were evaluated. The diagnosis was established according to the criteria of the World Brain Bank of Great Britain. The degree of clinical manifestations was assessed according to the unified rating scale for the assessment of Parkinson's disease modified by the International Society of Parkinson's Disease and Movement Disorders and the Hoehn and Yahr scale. The assessment of daily activity was carried out according to the scale of Schwab and England.
 To assess motor fluctuations and dyskinesia, we used the patients’ diary filled out on their own for 3 days before the visit to the clinic. According to the diary, the duration of the "off period" was determined over the treatment course. Depending on the form of the disease, the following groups were distinguished: group I including 40 patients with akinetic-rigid form; group II involved 40 patients with a mixed akinetic-rigid-tremor form. It has been found out that the onset of both forms of Parkinson's disease occurs mainly in old age, which is characterized by metabolic changes that may play a role in susceptibility to the therapy with levodopa drugs. These groups of patients demonstrated no statistically significant differences by the age, the age of the diseases onset, the duration of the disease and the duration of therapy with levodopa drugs, and the stage according to the Hen and Yar scale. According to the scale of Schwab and England, a higher level of dependence on assistance was revealed in group I compared to group II that may be caused by more pronounced motor disorders and motor fluctuations.
 The study has demonstrated that patients with various forms of Parkinson's disease show differences in the severity of movement disorders, in particular, in the quality of motor complications of levodopa therapy, manifested in the form of motor fluctuations, provided that clinical severity, duration of the disease and the use of levodopa drugs are matched. At the same time, different forms of Parkinson's disease do not differ in the prevalence of different types of motor fluctuations and require the development of new approaches to the correction of these conditions.

A DFT approach to the adsorption of the Levodopa anti-neurodegenerative drug on pristine and Al-doped boron nitride nanotubes as a drug delivery vehicle

The adsorption behavior of the anti-neurodegenerative drug Levodopa (LD) on pristine and aluminum-doped (Al-doped) boron nitride nanotubes (BNNTs) has been investigated in the current study using the density functional theory (DFT) approach at the B3LYP/6-31G** level of theory. The aim was to improve and expand boron nitride nanotubes drug carriers used in biomedical systems, i.e., drug delivery systems. The binding qualities of pure and doped BNNT complexes as adsorbents with LD were explored using the natural bond orbitals (NBO) analysis, density of state (DOS), electrical and structural characteristics, and atoms in molecules (AIM) properties. Due to doping heteroatoms in the adsorbent's molecular structure, the obtained data reveal a gradual shift in LD adsorption, with a significant rise in negative adsorption energy values. The electronic perturbation caused by doped atoms, particularly Al, improves boron nitride nanotube sensitivity to adsorbed Levodopa, and the electronic properties of the nanotubes are altered following Levodopa adsorption in the complex. As the frontier molecular orbital distributions were transferred from LD to BNNTs in the complex of BNNT–LD, it was also shown that LD drugs could be loaded on pristine and Al-doped BNNTs while remaining safe from interactions with other substances. Furthermore, AIM analysis based investigations revealed that O–Al interaction in LD adsorbed on Al-doped boron nitride nanotube and O–N interaction in the BNNT–LD complex are partially covalent. Finally, the findings showed that pristine and Al-doped BNNT could be used in drug delivery processes by controlling the loaded LD contribution to future interactions.

Preparation and detailed characterization of the thiomer chitosan–cysteine as a suitable mucoadhesive excipient for nasal powders

The therapeutic application of nasal powders requires the development of novel mucoadhesive excipients. Thiolated polymers exhibit significant potential for this purpose based on their increased mucoadhesion attributable to the formation of disulfide bonds between the polymer and mucus surface. A chitosan–cysteine (chit-cyst) conjugate was synthesized using 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide in aqueous solution. The synthetic yield and synthesis conditions were optimized, and the efficiency of the reaction was evaluated. Rheological measurements revealed that the polymer derivative exhibited increased mucoadhesive properties in comparison to chitosan powder. To characterize the polymer, a novel purity investigation method was developed and verified to investigate the residual l-cysteine content. The results revealed that l-cysteine was not detectable in the resultant polymer matrix. Based on the cytotoxicity studies, chit-cyst was found to be safe for nasal application. Thereafter, nasal powder formulations were prepared using the polymer and the antiparkinsonian drug levodopa methyl ester hydrochloride by freeze-drying to investigate their nasal applicability. Based on the in vitro studies, these powders might be suitable for reducing the off periods of Parkinson’s disease because of their expected higher in vivo mucoadhesion.

Fucoxanthin Prevents Long-Term Administration l-DOPA-Induced Neurotoxicity through the ERK/JNK-c-Jun System in 6-OHDA-Lesioned Mice and PC12 Cells.

As the most abundant marine carotenoid extracted from seaweeds, fucoxanthin is considered to have neuroprotective activity via its excellent antioxidant properties. Oxidative stress is regarded as an important starting factor for neuronal cell loss and necrosis, is one of the causes of Parkinson’s disease (PD), and is considered to be the cause of adverse reactions caused by the current PD commonly used treatment drug levodopa (l-DA). Supplementation with antioxidants early in PD can effectively prevent neurodegeneration and inhibit apoptosis in dopaminergic neurons. At present, the effect of fucoxanthin in improving the adverse effects triggered by long-term l-DA administration in PD patients is unclear. In the present study, we found that fucoxanthin can reduce cytotoxicity and suppress the high concentration of l-DA (200 μM)-mediated cell apoptosis in the 6-OHDA-induced PC12 cells through improving the reduction in mitochondrial membrane potential, suppressing ROS over-expression, and inhibiting active of ERK/JNK-c-Jun system and expression of caspase-3 protein. These results were demonstrated by PD mice with long-term administration of l-DA showing enhanced motor ability after intervention with fucoxanthin. Our data indicate that fucoxanthin may prove useful in the treatment of PD patients with long-term l-DA administration.