Vinay Sridhar - Academia.edu (original) (raw)

Papers by Vinay Sridhar

Journal of Drug Delivery Science and Technology, 2020

Abstract The nose-to-brain drug delivery theory has been verified by numerous studies. Previously... more Abstract The nose-to-brain drug delivery theory has been verified by numerous studies. Previously, we also demonstrated improved pharmacokinetics and pharmacodynamics of a selegiline thermosensitive gel in rats. Here, we developed a thermosensitive gel formulation of pramipexole and compared its anti-Parkinsonian effects with those of an orally administered pramipexole solution. The gel formulation containing 16% poloxamer 407 and 0.15% guar gum formed a stiff gel at 32–33 °C and released up to 95% of the drug within 8 h across goat nasal mucosa. Rotenone was administered at 3 mg/kg for 11 days to induce motor deficits, and pramipexole was administered as a post-treatment at 0.3 or 0.6 mg/kg for 10 days. Intranasally administered pramipexole gel effectively recovered locomotor activity scores, abolished catalepsy, increased the levels of brain glutathione and dopamine, and restored catalase activity to normal levels. The formulated pramipexole gel improved motor performance via its dopamine-agonistic activity and countered rotenone-induced oxidative damage to dopaminergic neurons, thereby restoring brain dopamine levels in rats. Intranasally administered low-dose pramipexole could be considered as a first-line therapy for Parkinson's disease.

AAPS PharmSciTech, 2018

Nelfinavir mesylate (NFV), a human immunodeficiency virus (HIV) protease inhibitor, is an integra... more Nelfinavir mesylate (NFV), a human immunodeficiency virus (HIV) protease inhibitor, is an integral component of highly active anti retro viral therapy (HAART) for management of AIDS. NFV possesses pH-dependent solubility and has low and variable bioavailability hampering its use in therapeutics. Lipid-based particulates have shown to improve solubility of poorly water soluble drugs and oral absorption, thereby aiding in improved bioavailability. The current study compares potential of vesicular and solid lipid nanocarriers of NFV with drug nanocrystallites and microvesicular systems like cochleates in improving bioavailability of NFV. The paper outlines investigation of systems using in vitro models like in vitro lipolysis, in vitro release, and permeation through cell lines to predict the in vivo potential of nanocarriers. Finally, in vivo pharmacokinetic study is reported which provided proof of concept in sync with results from in vitro studies.

Nanomedicine: Nanotechnology, Biology and Medicine, 2018

Selegiline, a well-known anti-Parkinson agent, is reported to be associated with poor oral bioava... more Selegiline, a well-known anti-Parkinson agent, is reported to be associated with poor oral bioavailability and safety. Therefore, we formulated selegiline as chitosan nanoparticles and evaluated its pharmacokinetics and pharmacodynamics after intranasal administration to rats relative to those after oral administration. The optimized formulation exhibited spherical nanoparticles with more than 90% drug loading and steady in vitro and ex vivo drug release. Selegiline concentrations in the brain and plasma were 20- and 12-fold higher, respectively, after intranasal administration than after oral administration. Treatment with intranasal nanoparticles was also associated with better performance in locomotor activity, catalepsy, and stride length tests and significantly increased dopamine, catalase activity, and glutathione content in the brain. Therefore, intranasally administered selegiline nanoparticles holds superior therapeutic value compared to oral administration and can be a promising approach for the treatment of Parkinson's disease.

International journal of biological macromolecules, Jan 13, 2017

In the current study, Pramipexole dihydrochloride loaded chitosan nanoparticles (P-CNs) were prep... more In the current study, Pramipexole dihydrochloride loaded chitosan nanoparticles (P-CNs) were prepared for Parkinson's disease via nose to brain pathway by ionic gelation method. Optimized P-CNs with chitosan and sodium tripolyphosphate (6:1 v/v) exhibited particle size and entrapment efficiency of 292.5 nm ± 8.80 and 91.25% ± 0.95 respectively and its diffusion across the artificial membrane and goat nasal mucosa was found to be 93.32% ± 2.56 and 83.03% ± 3.48 correspondingly after 24 h. Transmission electron microscopy displayed the spherical nature of the P-CNs particles and rough surface morphology was observed in scanning electron microphotographs. In pharmacodynamic studies, the comparative results of behavioral testing revealed improved score of photoactometer and reduced motor deficit in the form of catalepsy in P-CN treatment group as compare to its nasal solution or oral marketed tablets. Similarly, P-CNs enhanced antioxidant status in the form of increased superoxide d...

Journal of Drug Targeting, 2017

Selegiline hydrochloride (SL), is an Anti-Parkinson's agent, has low oral bioavailability due to ... more Selegiline hydrochloride (SL), is an Anti-Parkinson's agent, has low oral bioavailability due to its high first pass metabolism and scarce oral absorption. In the present study, SL mucoadhesive nasal thermosensitive gel (SNT-gel) was prepared to enhance the bioavailability and subsequently, its concentration in the brain. The SNT-gel was prepared using Poloxamer 407-Chitosan combination and optimized formulation was further evaluated for physicochemical parameters. The comparative pharmacodynamic studies including behavioral studies, biochemical testing and histopathology of the brain was carried out in rats for SNT-gel, SL-nasal solution and SL Marketed Tablets. The optimized SNT-gel formulation (SNT-V) revealed sol-gel transition at 33-34⁰C. In-vitro diffusion study of SNT-V showed 102.37±2.1% diffusion at 12 hrs which reduced to 89.64±1.2 % in Ex-vivo diffusion. Comparative results of behavioural studies indicated an improved score of photoactometer and reduced motor deficit (catalepsy score) in SNT-gel treatment group as compared with other groups. Similarly, a significant increase in brain dopamine, reduction in monoamine oxidase B level, increase in catalase activity and level of reduced glutathione upon treatment with SNT-gel indicated its effectiveness which was also supported by histopathology results. Therefore, nasal thermosensitive gel holds better potential for brain targeting in Parkinson's disease over the conventional nasal or oral formulations.

Toxicological Research, 2016

The impact of mobile phone (MP) radiation on the brain is of specific interest to the scientific ... more The impact of mobile phone (MP) radiation on the brain is of specific interest to the scientific community and warrants investigations, as MP is held close to the head. Studies on humans and rodents revealed hazards MP radiation associated such as brain tumors, impairment in cognition, hearing etc. Melatonin (MT) is an important modulator of CNS functioning and is a neural antioxidant hormone. Zebrafish has emerged as a popular model organism for CNS studies. Herein, we evaluated the impact of GSM900MP (GSM900MP) radiation exposure daily for 1 hr for 14 days with the SAR of 1.34 W/Kg on neurobehavioral and oxidative stress parameters in zebrafish. Our study revealed that, GSM900MP radiation exposure, significantly decreased time spent near social stimulus zone and increased total distance travelled, in social interaction test. In the novel tank dive test, the GSM900MP radiation exposure elicited anxiety as revealed by significantly increased time spent in bottom half; freezing bouts and duration and decreased distance travelled, average velocity, and number of entries to upper half of the tank. Exposed zebrafish spent less time in the novel arm of the Y-Maze, corroborating significant impairment in learning as compared to the control group. Exposure decreased superoxide dismutase (SOD), catalase (CAT) activities whereas, increased levels of reduced glutathione (GSH) and lipid peroxidation (LPO) was encountered showing compromised antioxidant defense. Treatment with MT significantly reversed the above neurobehavioral and oxidative derangements induced by GSM900MP radiation exposure. This study traced GSM900MP radiation exposure induced neurobehavioral aberrations and alterations in brain oxidative status. Furthermore, MT proved to be a promising therapeutic candidate in ameliorating such outcomes in zebrafish.

RSC Advances, 2016