Browsing by Author "Taliyan, Rajeev"

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Advances in Antibody-Based Therapeutics for Cerebral Ischemia
(MDPI, 2022-12) Taliyan, Rajeev
Cerebral ischemia is an acute disorder characterized by an abrupt reduction in blood flow that results in immediate deprivation of both glucose and oxygen. The main types of cerebral ischemia are ischemic and hemorrhagic stroke. When a stroke occurs, several signaling pathways are activated, comprising necrosis, apoptosis, and autophagy as well as glial activation and white matter injury, which leads to neuronal cell death. Current treatments for strokes include challenging mechanical thrombectomy or tissue plasminogen activator, which increase the danger of cerebral bleeding, brain edema, and cerebral damage, limiting their usage in clinical settings. Monoclonal antibody therapy has proven to be effective and safe in the treatment of a variety of neurological disorders. In contrast, the evidence for stroke therapy is minimal. Recently, Clone MTS510 antibody targeting toll-like receptor-4 (TLR4) protein, ASC06-IgG1 antibody targeting acid sensing ion channel-1a (ASIC1a) protein, Anti-GluN1 antibodies targeting N-methyl-D-aspartate (NMDA) receptor associated calcium influx, GSK249320 antibody targeting myelin-associated glycoprotein (MAG), anti-High Mobility Group Box-1 antibody targeting high mobility group box-1 (HMGB1) are currently under clinical trials for cerebral ischemia treatment. In this article, we review the current antibody-based pharmaceuticals for neurological diseases, the use of antibody drugs in stroke, strategies to improve the efficacy of antibody therapeutics in cerebral ischemia, and the recent advancement of antibody drugs in clinical practice. Overall, we highlight the need of enhancing blood–brain barrier (BBB) penetration for the improvement of antibody-based therapeutics in the brain, which could greatly enhance the antibody medications for cerebral ischemia in clinical practice.
Age-related changes in gonadotropin-releasing hormone (GnRH) splice variants in mouse brain
(Wiley, 2022-11) Taliyan, Rajeev
Gonadotropin-releasing hormone (GnRH) is the primary regulator of the mammalian reproductive axis. We investigated the spatiotemporal expression of GnRH splice variants (V1, V2, and V3) and splicing factors (Srsf7, Srsf9, and Tra-2) in the male mice brain. Further, using in silico tools, we predicted protein structure and the reason for the low translational efficiency of V2 and V3. Messenger RNA levels of GnRH variants and splicing factors were quantified using real-time reverse transcription-polymerase chain reaction at different age groups. Our data show that expression of almost all the variants alters with aging in all the brain regions studied; even in comparison to the hypothalamus, several brain areas were found to have higher expression of these variants. Hypothalamic expression of splicing factors such as Srsf7, Srsf9, and Tra-2 also change with aging. Computational studies have translation repressors site on the V3, which probably reduces its translation efficiency. Also, V2 is an intrinsically disordered protein that might have a regulatory or signaling function. In conclusion, this study provides novel crucial information and multiple starting points for future analysis of GnRH splice variants in the brain.
Antibody–Drug Conjugates: Development and Applications
(Wiley, 2022-11) Taliyan, Rajeev; Singhvi, Gautam
Antibody–drug conjugates (ADCs) are relatively newly developed treatments but rapidly growing science. Theoretically, they are like a combination of payload (the drug that is to be delivered; often cytotoxic) and targeted drug-delivery system. In this type of system, the cytotoxic drug undergoes conjugation with a monoclonal antibody via a chemical linker. The fundamental design of ADCs imparts desired properties to the delivery system, such as physiochemical strength, biodegradable nature, and biocompatibility. This plays a crucial role in the management of diseases via offering numerous benefits, such as high drug loading, less incidence of adverse effects, site-specific release, and longer circulation time in the body. In this review, the recent advancements in the preparation of ADCs (including recently approved ADCs), pharmacokinetics, their applications, and regulatory consideration have been summarized. Further, it also provides a discussion on the future status of this therapy for the treatment and management of oncological conditions.
Back Cover: Preclinical pharmacokinetics of trigonelline using ultra-performance liquid chromatography–tandem mass spectrometry and pharmacological studies targeting type 2 diabetes
(Wiley, 2021-04) Taliyan, Rajeev
The cover picture shows, Trigonelline (Tr) a quaternary base alkaloid, which acts by affecting β-cell regeneration and insulin secretion. Tr lowers the blood glucose and lipid levels due to which it is used in the treatment of co-morbid diseases. Herein, we have aimed to develop a bioanalytical method for estimation of Tr using UPLC-MS/MS and explore the pharmacokinetic profile. The anti-diabetic, antilipidemic efficacy studies were also conducted in the high-fat diet-induced streptozotocin-diabetic rat. The experimental results suggest that Tr follow the two compartmental pharmacokinetic model. In addition, Tr exhibited a significant anti-hyperglycemic and antihyperlipidemic efficacy in high-fat diet-induced streptozotocin induced diabetic rats.
Beneficial Effect of Cyclosporine in Experimental Diabetes Induced Neuropathic Pain in Rats
(Science Alert, 2010) Taliyan, Rajeev
The present study was designed to investigate the effect of cyclosporine on hyperglycemia induced decrease antinociceptive effect of morphine in rats. Streptozotocin (STZ) (50 mg kg-1, i.p., once) was administered to induce experimental diabetes in the rats. Pain sensitivity was measured using tail-flick and paw withdrawal test. Urinary and serum nitrite concentration was estimated using Greiss reagent. Spleen Homogenate Supernatant (SHS) was prepared from spleen of 28th day diabetic rats and administered to normal rats (400 μL. i.v.) for 28 days. Experimental diabetes significantly decreased paw withdrawal latency to thermal stimuli on day 28 as compared to age matched control rats, indicating that diabetic rats exhibit thermal hyperalgesia. Moreover, analgesic effect of morphine (4 and 8 mg kg-1 s.c.), was progressively decreased in diabetic and SHS treated non diabetic rats. Further, the levels of nitric oxide were also elevated in 28th day diabetic and SHS treated non diabetic rats. However, administration of Cyclosporine (12.5 and 25 mg kg-1 i.p.), an IL-2 inhibitor and splenectomy attenuated diabetes and SHS induced decrease in nociceptive threshold and increase in serum and urinary nitrite levels. It is concluded that cyclosporine have beneficial effect in diabetic neuropathy and also improved the analgesic effect of morphine.
Beneficial effects of sodium butyrate in 6-OHDA induced neurotoxicity and behavioral abnormalities: modulation of histone deacetylase activity
(Elsevier, 2015-09) Taliyan, Rajeev
Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Recent studies have investigated the involvement of epigenetic modifications in PD. Histone deacetylase (HDAC) inhibitors have been reported to be beneficial in cognitive and motor deficit states. The present study was designed to investigate the effect of sodium butyrate, a HDAC inhibitor in 6-hydroxydopamine (6-OHDA) – induced experimental PD like symptoms in rats. To produce motor deficit, 6-OHDA was administered unilaterally in the right medial forebrain bundle. Three weeks after 6-OHDA administration, the rats were challenged with apomorphine. Following this, the animals were treated with sodium butyrate (150 and 300 mg/kg i.p.) once daily for 14 days. Movement abnormalities were assessed by battery of behavioral tests. Biochemically, oxidative stress markers, neuroinflammation and dopamine were measured in striatal brain homogenate. Further, to explore the molecular mechanism(s), we measured the level of global H3 histone acetylation and brain derived neurotrophic factor (BDNF). 6-OHDA administration results in significant motor deficit along with reduction in striatal dopamine level. 6-OHDA treated rats showed elevated oxidative stress and neuroinflammatory markers. Treatment with sodium butyrate results in significant attenuation of motor deficits and increased striatal dopamine level. Moreover, sodium butyrate treatment attenuated the oxidative stress and neuroinflammatory markers. These effects occur concurrently with increased global H3 histone acetylation and BDNF levels. Thus, the observed results of the present study are indicative for the therapeutic potential of HDAC inhibitors in PD.
Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disorders
(Elsevier, 2025-01) Taliyan, Rajeev
Psychiatric disorders pose a significant global health challenge, exacerbated by the COVID-19 pandemic and insufficiently addressed by the current treatments. This review explores the emerging role of bile acids and the TGR5 receptor in the pathophysiology of psychiatric conditions, emphasizing their signaling within the gut-brain axis. We detail the synthesis and systemic functions of bile acids, their transformation by gut microbiota, and their impact across various neuropsychiatric disorders, including major depressive disorder, general anxiety disorder, schizophrenia, autism spectrum disorder, and bipolar disorder. The review highlights how dysbiosis and altered bile acid metabolism contribute to the development and exacerbation of these neuropsychiatric disorders through mechanisms involving inflammation, oxidative stress, and neurotransmitter dysregulation. Importantly, we detail both pharmacological and non-pharmacological interventions that modulate TGR5 signaling, offering potential breakthroughs in treatment strategies. These include dietary adjustments to enhance beneficial bile acids production and the use of specific TGR5 agonists that have shown promise in preclinical and clinical settings for their regulatory effects on critical pathways such as cAMP-PKA, NRF2-mediated antioxidant responses, and neuroinflammation. By integrating findings from the dynamics of gut microbiota, bile acids metabolism, and TGR5 receptor related signaling events, this review underscores cutting-edge therapeutic approaches poised to revolutionize the management and treatment of psychiatric disorders.
Bio-Interface Analysis and Detection of Aβ using GaN HEMT-based Biosensor
(IOP, 2024) Taliyan, Rajeev
Early detection, prognosis, and diagnosis of devastating neurological disorders such as TBI and AD are crucial for developing treatment strategies, efficient patient outcomes, and management in biomedical fields. The work reports the design, development, suitability analysis, and validation of a label-free GaN HEMT-based biosensing platform for the non-invasive detection of FDA-approved biomarker Aβ in saliva sample concentration ranges. The biofunctionalization assay has been validated with both electrical and FTIR spectroscopy-based measurements. A comparative analysis with ELISA assay shows good agreement with ∼2.0% measurement errors demonstrating platform stability and accuracy for Aβ detection. The platform offers a peak sensitivity of 27.20 μA/pg ml−1, 19.10 μA pg−1 ml−1, and 1.48 μA/pg ml−1 for detection in saliva, serum, and CSF concentration ranges with high specificity, excellent repeatability, and reproducibility of the results. The platform offers a sensitivity of 2.40 μA/pg ml−1, 15.40 μA pg−1 ml−1, and 27.20 μA/pg ml−1 for Sbias of 1.0 V, 3.3 V, and 5.0 V respectively. The key biosensor features include fast detection with a response time of 5–10 s and a low sample volume requirement of ∼1–2 μl. The platform comparison with ELISA shows a similar and acceptable linearity trend. A novel equation has been established for ELISA and developed platform-based detection for possible detection accuracy and validation useful for correlating the sensor response with ELISA test results and vice-versa for any target Aβ concentrations. To the best of our knowledge, this is the first time reporting of Aβ detection using a GaN HEMT-based biosensing platform.
Bioanalytical methodologies for clinical investigation of endocrine-disrupting chemicals: a comprehensive update
(Future Science Group, 2021-01) Taliyan, Rajeev; Singhvi, Gautam
Endocrine-disrupting chemicals (EDCs) are xenobiotics that disrupt the endocrine system in humans at ecologically significant concentrations. Various substances are exposed to human health via routes including food, water, air and skin that result in disastrous maladies at low doses as well. Therefore EDCs need a meticulous strategy of analysis for dependable and consistent monitoring in humans. The management and risk assessment necessitate advancements in the detection methodologies of EDCs. Hyphenated MS-based chromatograph and other validated laboratory analysis methods are widely available and employed. Besides, in vitro bioassay techniques and biosensors are also used to conduct accurate toxicological tests. This article provides a revision of various bioanalytical detection methods and technologies for the clinical estimation of EDCs.
Biological toxicity of nanoparticles
(Elsevier, 2022) Taliyan, Rajeev
Multiple biological barriers and discrepancy in releasing the optimal dosage range pose a great challenge in the current therapeutic management for majority of diseases. Nanoparticle drug delivery system (5–250 nm) possesses the capacity to overcome such difficulties making it an incredible choice for disease management. Various types of nanoparticles are readily available in the market each possessing its own unique characteristics, however, based on their size, shape, and surface reactivity, they can inflict certain type of toxicity, the most common being biological toxicity to human tissue and to cell culture. The toxicity can further lead to an enhanced level of oxidative stress and inflammatory cytokine. Hence, in the following chapter, we discuss the various types of nanoparticles available, its importance in the clinical field and a detailed understanding on the biological toxicity of nanoparticles.
Brain insulin resistance linked Alzheimer’s and Parkinson’s disease pathology: An undying implication of epigenetic and autophagy modulation
(Springer, 2023-03) Taliyan, Rajeev
In metabolic syndrome, dysregulated signalling activity of the insulin receptor pathway in the brain due to persistent insulin resistance (IR) condition in the periphery may lead to brain IR (BIR) development. BIR causes an upsurge in the activity of glycogen synthase kinase-3 beta, increased amyloid beta (Aβ) accumulation, hyperphosphorylation of tau, aggravated formation of Aβ oligomers and simultaneously neurofibrillary tangle formation, all of which are believed to be direct contributors in Alzheimer’s Disease (AD) pathology. Likewise, for Parkinson’s Disease (PD), BIR is associated with alpha-synuclein alterations, dopamine loss in brain areas which ultimately succumbs towards the appearance of classical motor symptoms corresponding to the typical PD phenotype. Modulation of the autophagy process for clearing misfolded proteins and alteration in histone proteins to alleviate disease progression in BIR-linked AD and PD have recently evolved as a research hotspot, as the majority of the autophagy-related proteins are believed to be regulated by histone posttranslational modifications. Hence, this review will provide a timely update on the possible mechanism(s) converging towards BIR induce AD and PD. Further, emphasis on the potential epigenetic regulation of autophagy that can be effectively targeted for devising a complete therapeutic cure for BIR-induced AD and PD will also be reviewed.
Chitinase-3-like-1: a multifaceted player in neuroinflammation and degenerative pathologies with therapeutic implications
(Springer, 2025-01) Taliyan, Rajeev
Chitinase-3-like-1 (CHI3L1) is an evolutionarily conserved protein involved in key biological processes, including tissue remodeling, angiogenesis, and neuroinflammation. It has emerged as a significant player in various neurodegenerative diseases and brain disorders. Elevated CHI3L1 levels have been observed in neurological conditions such as traumatic brain injury (TBI), Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease (CJD), multiple sclerosis (MS), Neuromyelitis optica (NMO), HIV-associated dementia (HAD), Cerebral ischemic stroke (CIS), and brain tumors. This review explores the role of CHI3L1 in the pathogenesis of these disorders, with a focus on its contributions to neuroinflammation, immune cell infiltration, and neuronal degeneration. As a key regulator of neuroinflammation, CHI3L1 modulates microglia and astrocyte activity, driving the release of proinflammatory cytokines that exacerbate disease progression. In addition to its role in disease pathology, CHI3L1 has emerged as a promising biomarker for the diagnosis and monitoring of brain disorders. Elevated cerebrospinal fluid (CSF) levels of CHI3L1 have been linked to disease severity and cognitive decline, particularly in AD and MS, highlighting its potential for clinical diagnostics. Furthermore, therapeutic strategies targeting CHI3L1, such as small-molecule inhibitors and neutralizing antibodies, have shown promise in preclinical studies, demonstrating reduced neuroinflammation, amyloid plaque accumulation, and improved neuronal survival. Despite its therapeutic potential, challenges remain in developing selective and safe CHI3L1-targeted therapies, particularly in ensuring effective delivery across the blood–brain barrier and mitigating off-target effects. This review addresses the complexities of targeting CHI3L1, highlights its potential in precision medicine, and outlines future research directions aimed at unlocking its full therapeutic potential in treating neurodegenerative diseases and brain pathologies.
Chronic Light-Distorted Glutamate-Cortisol Signaling, Behavioral and Histological Markers, and Induced Oxidative Stress and Dementia: An Amelioration by Melatonin
(ACS, 2022-05) Taliyan, Rajeev
The present work aimed to investigate the induction of circadian rhythm dysfunction and dementia upon chronic exposure to light–light and its reversal by melatonin in Wistar rats. Animals underwent different light–dark conditions, viz., light/dark (LD), light/light (LL), and dark/dark (DD) in respective groups for 4 months. Melatonin 0.5 mg/kg s.c., dextromethorphan 50 μg/100 g s.c., and mifepristone 25 μg/100 g s.c. were given once a day. Chronic LL and DD conditions significantly increased brain glutamate and cortisol levels. The LL period caused a deficit in spatial memory, working memory, decision making, and exploration of novel objects, compared to LD animals. A significant (p < 0.05) change in neuropathological observations in the hippocampus, CA1, CA2, and CA3; cortex; and cerebellum regions (40×, 100×, and 400×) was observed in the histological study. Induced oxidative stress in brain tissue was also observed by estimating tissue glutathione and TBARS levels. Dextromethorphan (NMDA antagonist), mifepristone (corticosterone antagonist), and melatonin significantly (p < 0.05) reversed the pathological states caused due to LL. The histological features in the hippocampus, cortex, and cerebellum region revealed inflammatory cells, vacuolation, and pyknotic cells, which were significantly rescued by antagonizing NMDA or cortisol or melatonin treatment. It may be concluded that continuous exposure to light–light conditions produced an imbalance between neuronal excitation and stress hormone, leading to poor cognitive abilities and neuropathology.
Comprehensive Review on Potential Signaling Pathways Involving the Transfer of α-Synuclein from the Gut to the Brain That Leads to Parkinson’s Disease
(ACS, 2023-02) Taliyan, Rajeev
Parkinson’s disease is the second most prevalent neurological disease after Alzheimer’s. Primarily, old age males are more affected than females. The aggregates of oligomeric forms of α-synuclein cause the loss of dopaminergic neurons in the substantia nigra pars compacta. Further, it leads to dopamine shortage in the striatum region. According to recent preclinical studies, environmental factors like pesticides, food supplements, pathogens, etc. enter the body through the mouth or nose and ultimately reach the gut. Further, these factors get accumulated in enteric nervous system which leads to misfolding of α-synuclein gene, and aggregation of this gene results in Lewy pathology in the gut and reaches to the brain through the vagus nerve. This evidence showed a strong bidirectional connection between the gut and the brain, which leads to gastrointestinal problems in Parkinson patients. Moreover, several studies reveal that patients with Parkinson experience more gastrointestinal issues in the early stages of the disease, such as constipation, increased motility, gut inflammation, etc. This review article focuses on the transmission of α-synuclein and the mechanisms involved in the link between the gut and the brain in Parkinson’s disease. Also, this review explores the various pathways involved in Parkinson and current therapeutic approaches for the improvement of Parkinson’s disease.
Delayed neuroprotection against cerebral ischemia reperfusion injury: putative role of BDNF and GSK-3β
(Taylor & Francis, 2015-11) Taliyan, Rajeev
Numerous studies have demonstrated the possible neuroprotective role of lithium treatment against neurological disorders. However, the role of lithium in delayed phase of neuronal death against focal ischemia has not been explored. Therefore, the present study was designed to investigate the effect and molecular mechanisms of post-lithium treatment against cerebral ischemic reperfusion (I/R) injury and associated cognitive deficits in rats. Methods: I/R injury was induced by right middle cerebral artery occlusion and lithium (40 and 60 mg/kg) were given intraperitoneally, 24 h after the insult and continued for 1 week with 24-h interval. Using Lasser Doppler, cerebral blood flow was monitored before, during and after MCAO induction. Besides behavioral, biochemical, and histological evaluation, levels of tumor necrosis factor alpha (TNF-α) and brain-derived neurotrophic factor (BDNF) were also estimated. Results: I/R injury resulted in significant elevation of neurological deficits, oxidative stress, neuroinflammation, and cognitive impairments. We found that lithium injection, 24 h after I/R-injury continued for 1 week, dose dependently prevented behavioral abnormality and cognitive impairments. Moreover, lithium attenuated the levels of oxidative stress and pro-inflammatory-cytokines TNF-α level. Further, lithium treatments significantly reduced neuronal damage and augmented healthy neuronal count and improved neuronal density in hippocampus. These neuroprotective effects of delayed lithium treatment were associated with upregulation of neurotrophic factor BDNF levels. Conclusion: Delayed lithium treatment provides neuroprotection against cerebral I/R injury and associated cognitive deficits by upregulating BDNF expression that opens a new avenue to treat I/R injury even after active cell death.
Design and biological evaluation of Repaglinide loaded polymeric nanocarriers for diabetes linked neurodegenerative disorder: QbD-driven optimization, in situ, in vitro and in vivo investigation
(Elsevier, 2023-04) Taliyan, Rajeev
Diabetes mellitus is a metabolic disorder characterized by inadequate insulin secretion and signaling dysfunction, leading to a vast spectrum of systemic complications. These complications trigger cascades of events that result in amyloid-beta plaque formation and lead to neurodegenerative disorders such as Alzheimer’s. Repaglinide (REP) an insulinotropic agent, suppresses the down regulatory element antagonist modulator (DREAM) and enhances the ATF6 expression to provide neuroprotection following the DREAM/ATF6/apoptotic pathway. However, oral administration of REP for brain delivery becomes more complicated due to its physicochemical characteristics (high protein binding (>98%), low permeability, short half-life (∼1 h), low bioavailability). Therefore, to circumvent these problems, we develop a polymeric nanocarrier system (PNPs) by in-house synthesized di-block copolymer (PEG-PCL). PNPs were optimized using quality by design approach response surface methodology and characterized by particle size (112.53 ± 5.91 nm), PDI (0.157 ± 0.08), and zeta potential (−6.20 ± 0.82 mV). In vitro release study revealed that PNPs (∼70% in 48 h) followed the Korsmeyer-Peppas model with a Fickian diffusion release pattern, and in intestinal absorption assay PNPs showed increment of ∼1.3 folds compared of REP. Moreover, cellular studies confirmed that REP-loaded PNPs significantly enhance the cellular viability, uptake and reduce the peroxide-induced stress in neuroblastoma SHSY-5Y cells. Further, pharmacokinetic parameters of PNPs showed an increment in tmax (2.46-fold), and Cmax (1.25-fold) associated with REP. In the brain biodistribution study, REP loaded PNPs was sustained for 24 h whereas free REP sustained only for12 h. In DM induced neurodegenerative murine model, a significantly (p < 0.01) enhanced pharmacodynamic was observed in PNP treated group by estimating biochemical and behavioral parameters. Hence, oral administration of REP-loaded PNPs promotes efficient brain uptake and improved efficacy of REP in the diseased model
Design aspects, development, and sensitivity analysis of gan hemt-based biosensing platform for label-free detection of interleukin-6
(IOP, 2025) Taliyan, Rajeev
Severe TBI survivors face long-term brain damage requiring accurate diagnosis and early treatment as the therapeutic time window typically ranges from minutes to hours before the secondary injury. In this work, we report design aspects and development of an ultrasensitive GaN HEMT-based biosensing platform for IL-6 detection along with novel design correlation equations for sensitivity analysis. Design analysis reveals that the lower value of is desirable for enhanced sensitivity as the biosensor with of 10 μm offers a peak sensitivity of 129.20 μA pg−1 ml−1 as compared to 25 and 50 μm with a sensitivity of 70.76 and 35.60 μA pg−1 ml−1 respectively. Furthermore, the peak sensitivity reaches as high as 158.01 μA pg−1 ml−1 when the was increased from 100 to 250 μm for biosensors with of 10 μm using conventional gate design. An increase in sensitivity from 70.76 to 88.40 μA pg−1 ml−1 was observed when a meander gate biosensor was used. An analysis of the EDC-NHS coupling process reveals an enhancement in sensitivity from 78.60 to 129.20 μA pg−1 ml−1 for the EDC-NHS coupled biosensor. The peak response of the biosensor for IL-6 detection was observed at 5 min after the drop cast of antigens over the sensing areas.
Development and validation of a stability-indicating reversed-phase–high-performance liquid chromatography method for quantification of 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a from lipid-polymeric hybrid nanoparticles
(Wiley, 2022-12) Taliyan, Rajeev
2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a is a second-generation, lipophilic, chlorin-based photosensitizer currently used for various types of solid cancer including breast, esophageal, neck, and head cancer, etc. The aim of the present work was to develop a sensitive and robust reversed-phase–high-performance liquid chromatography–ultraviolet detection method for the determination of 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a to explore in vitro-based applications including encapsulation, loading, drug release, and stability studies, and also could be utilized for the selective analysis of 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a from developed lipid polymer hybrid nanoparticle. The developed reversed-phase–high-performance liquid chromatography–ultraviolet detection method was validated in terms of linearity, accuracy, precision, stability, and robustness as per standard guidelines. The developed method exhibited linearity ranging from 50 to 2000 ng/ml with an R2 value of 0.999. The limit of detection and limit of quantitation value of the developed method was found to be 14.03 and 42.80 ng/ml, respectively. Also, degradation studies revealed that 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a degraded quickly under basic conditions compared to other stability conditions (i.e., acidic, oxidative, temperature, etc.). Furthermore, the developed drug-loaded lipid polymer hybrid nanoparticle showed an average size of 123.03 nm (polydispersity index = 0.253) with an encapsulation efficiency of 70.23%. Cell cytotoxicity assay of lipid polymer hybrid nanoparticle showed significant cancer cell death equivalent to 2-fold higher than the free drug. In conclusion, the developed reversed-phase–high-performance liquid chromatography–ultraviolet detection analytical method was found to be sensitive and reliable for the determination of free 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a and 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a content in loaded lipid polymer hybrid nanoparticle. Thereby, opening the avenues for future research to explore the detailed physiochemical and formulation designing for the 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a.
Development and Validation of PEG-PCL Based Nanoformulation of Rosiglitazone and Evaluation of its Brain Selectivity in Mice Model of Alzheimer’s disease
(Alzheimer's Association, 2021-12) Taliyan, Rajeev
Type-2 Diabetes Mellitus and insulin resistance increases the risk of Alzheimer’s disease (AD). Recent studies highlighted the role of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in modulation of AD. This study was designed to investigate the effect of rosiglitazone alone or in its nanoformulated form for an effective drug delivery in mice model of AD.
Development and validation of RP-HPLC method for quantification of repaglinide in mPEG-PCL polymeric nanoparticles: QbD-driven optimization, force degradation study, and assessment of in vitro release mathematic modeling
(Elsevier, 2021-09) Taliyan, Rajeev
Repaglinide (REP) an insulinotropic agent used in the treatment of type-2 diabetes. It belongs to meglitinides, which act by blocking the ATP sensitive potassium channels and stimulates the insulin release. REP is the first insulin secretagogue used to target postprandial hyperglycemia. In this study, a rapid, sensitive, and reproducible RP-HPLC method has been developed and validated using an analytical quality-by-design approach. Initially, the Ishikawa fishbone diagram provides the basis of variation in critical analytical attributes with various inputs. Additionally, Taguchi design was selected to screen the critical method parameters affecting method development. Further, systemic optimization of the RP-HPLC method was determined by using Box-Behnken design. The chromatography separation was achieved by acetonitrile and phosphate buffer (60:40) with isocratic flow system on waters Nova-pack C18 column (3.9 × 150 mm, 4 μm) with 0.8 mL/min flow rate and the developed method was validated as per ICH guidelines. Moreover, the force degradation studies were also performed under different conditions (acidic, basic, oxidation and photolytic) to understand the degradation pathways and products. Furthermore, an amphiphilic di-block biodegradable polymer, i.e., polyethylene glycol-polycaprolactone (mPEG-PCL) was synthesized with different molecular weights to encapsulate REP and understand the release kinetics with mathematical modeling. In addition, the validated RP-HPLC method was effectively utilized to determine percent entrapment efficiency and loading efficiency of REP loaded nanoparticles. The developed method would also be applicable to quantify the REP from the biological matrix.