BITS Faculty Publications
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Item Engineering of structural and functional properties of nanotherapeutics and nanodiagnostics for intranasal brain targeting in Alzheimer's(Elsevier, 2022-03) Pandey, Murali MonoharAlzheimer's disease (AD) is the fifth leading cause of death on the planet. It hallmarks the presence of amyloid plaques and neurofibrillary tangles in geriatric patients. The condition witnesses early stages of mild dementia and learning inabilities. It progressively culminates into impaired behavioural functions, cognitive inability and impaired memory functions. Also, the COVID-19 pandemic has raised new concerns for AD patients as they are at higher risk of infection with COVID-19 than non-AD patients. The increasing toll of Alzheimer's patients is alarming a need for effective and safe therapeutics. This review discusses the various nanocarriers in delivering therapeutics for Alzheimer's via the intranasal route. Nanocarrier based therapeutic, diagnostic and theragnostic applications concerning AD have been covered. The review also discusses the nasal transport pathways and nanocarrier characteristics' role in cellular uptake mechanism. We have briefly discussed the potential biomarkers, imaging modalities, nano vaccines, advanced theragnostic probes, and related clinical studies. Lastly, we discussed the prospects concerning the development of intranasal nanodiagnostics and nanotherapeutics in Alzheimer's. Overall, this review summarizes various intranasal brain targeting strategies in AD.Item Nose-to-brain delivery of rotigotine redispersible nanosuspension: In vitro and in vivo characterization(Elsevier, 2023-01) Pandey, Murali MonoharRotigotine (RTG) is an anti-Parkinson's drug approved by the USFDA to treat motor and non-motor symptoms of both early and advanced stages of the disease. However, issues like poor aqueous solubility, low oral bioavailability (<1%), first-pass metabolism, low systemic bioavailability (∼37%) and low brain bioavailability demean the therapy. This work developed poloxamer-stabilized RTG-Nanosuspension for intranasal (i.n.) administration. RTG-Nanosuspension was optimized using Box-Behnken design with critical variables affecting the responses, viz. particle size and PDI. The optimized RTG-Nanosuspension showed mean particle size of 73 nm and PDI of 0.286. Lyophilized RTG-Nanosuspension was also characterized for drug crystallinity, interactions, and morphology. The lyophilized RTG-Nanosuspension showed good stability and was a porous structure. The first 15 min of in vitro dissolution showed 95% cumulative drug dissolved from RTG-Nanosuspension formulation. RTG-Nanosuspension showed 20-fold increase in nasal permeation. The nasal ciliotoxicity study showed both RTG-Nanosuspension and drug dispersion were safe for i.n. delivery. An in vivo study showed that optimized RTG-Nanosuspension helped target RTG to the brain following i.n. administration. Overall, the RTG-Nanosuspension formulation showed potential in nose-to-brain delivery for targeted application in Parkinson's disease.Item Intranasal nanotherapeutics for brain targeting and clinical studies in Parkinson's disease(Elsevier, 2023-06) Pandey, Murali MonoharParkinson's disease (PD) is the second leading neurodegenerative disease globally, impacting the quality of life of millions of people. It is estimated that the treatment cost of PD in the USA can rise to 79 billion dollars by 2037. Limited drugs are approved by USFDA, which only provides symptomatic relief. Further, the drug efficacy is challenged due to low drug-brain concentration due to first-pass metabolism and blood-brain barrier (BBB). Intranasal drug administration can offer several advantages over systemic administration, providing efficient brain delivery. Nose-to-brain (N2B) drug delivery can enhance brain bioavailability, reduce enzymatic degradation, and reduce systemic adverse effects. However, due to poor absorption from the nasal mucosa, intranasal administration can be challenging for hydrophilic drugs. The drug mucociliary clearance, retention time, and nasal enzymatic degradation can also affect N2B drug delivery. Nanocarriers can enhance residence time, improve nasal permeation, increase brain uptake, and reduce enzymatic degradation. This review discusses the roles and applications of various N2B nanocarriers to treat PD effectively. Clinical trials of antiparkinson molecules is also covered. Lastly, safety aspects and prospects of potential nanotherapeutics for the effective treatment of PD are discussed.Item Self-Assembled Lecithin-Chitosan Nanoparticles Improved Rotigotine Nose-to-Brain Delivery and Brain Targeting Efficiency(MDPI, 2023-03) Chitkara, Deepak; Pandey, Murali MonoharRotigotine (RTG) is a non-ergoline dopamine agonist and an approved drug for treating Parkinson’s disease. However, its clinical use is limited due to various problems, viz. poor oral bioavailability (<1%), low aqueous solubility, and extensive first-pass metabolism. In this study, rotigotine-loaded lecithin-chitosan nanoparticles (RTG-LCNP) were formulated to enhance its nose-to-brain delivery. RTG-LCNP was prepared by self-assembly of chitosan and lecithin due to ionic interactions. The optimized RTG-LCNP had an average diameter of 108 nm with 14.43 ± 2.77% drug loading. RTG-LCNP exhibited spherical morphology and good storage stability. Intranasal RTG-LCNP improved the brain availability of RTG by 7.86 fold with a 3.84-fold increase in the peak brain drug concentration (Cmax(brain)) compared to intranasal drug suspensions. Further, the intranasal RTG-LCNP significantly reduced the peak plasma drug concentration (Cmax(plasma)) compared to intranasal RTG suspensions. The direct drug transport percentage (DTP (%)) of optimized RTG-LCNP was found to be 97.3%, which shows effective direct nose-to-brain drug uptake and good targeting efficiency. In conclusion, RTG-LCNP enhanced drug brain availability, showing the potential for clinical application.