Nanotechnological advances in the treatment of epilepsy: a comprehensive review.

Epilepsy is one of the most prevalent chronic neurological disorders characterized by frequent unprovoked epileptic seizures. Epileptic seizures can develop from a broad range of underlying abnormalities such as tumours, strokes, infections, traumatic brain injury, developmental abnormalities, autoimmune diseases, and genetic predispositions. Sometimes epilepsy is not easily diagnosed and treated due to the large diversity of symptoms. Undiagnosed and untreated seizures deteriorate over time, impair cognition, lead to injuries, and can sometimes result in death. This review gives details about epilepsy, its classification on the basis of International League Against Epilepsy, current therapeutics which are presently offered for the treatment of epilepsy. Despite of the fact that more than 30 different anti-epileptic medication and antiseizure drugs are available, large number of epileptic patients fail to attain prolonged seizure independence. Poor onsite bioavailability of drugs due to blood brain barrier poses a major challenge in drug delivery to brain. The present review covers the limitations with the state-of-the-art strategies for managing seizures and emphasizes the role of nanotechnology in overcoming these issues. Various nano-carriers like polymeric nanoparticles, dendrimers, lipidic nanoparticles such as solid lipid nanoparticles, nano-lipid carriers, have been explored for the delivery of anti-epileptic drugs to brain using oral and intranasal routes. Nano-carries protect the encapsulated drugs from degradation and provide a platform to deliver controlled release over prolonged periods, improved permeability and bioavailability at the site of action. The review also emphasises in details about the role of neuropeptides for the treatment of epilepsy.

Polysorbate 80 surface modified PLGA nanoparticles: an in-vitro evaluation of cellular uptake and cytotoxicity on neuro-2a cells.

AIM: Present study focuses on the development of P80 coated PLGA Nanoparticles loaded with drugs, paroxetine (P80-Par-PLGA-NPs) and clonidine (P80-CLD-PLGA-NPs) for in-vitro evaluation of Cellular Uptake & Cytotoxicity on Neuro-2a cells. METHOD: P80-Par-PLGA-NPs and P80-CLD-PLGA-NPs were developed and characterised for zeta size, potential, PDI, EE%, DL%, TEM, SEM, FTIR, DSC, in-vitro release, cytotoxicity, histopathological and cell uptake studies using rhodamine loaded P80-NPs. RESULT: Mean particle diameter of P80-Par-PLGA-NPs and P80-CLD-PLGA-NPs was 204; 182.7 nm, ZP of -21.8; -18.72 mV and 0.275; 0.341 PDI, respectively. TEM and SEM images revealed homogenous surface morphology. In-vitro drug release showed sustained and complete release in 72 h. Cell viability (>90%) at Cmax and no cytotoxicity in histopathology was observed. Significant higher uptake (96.9%) of P80-modified-NPS was observed as compared to unmodified-NPs (81%) (p < 0.05). CONCLUSION: The finding clearly indicated a higher cell uptake of drugs via surface modified P80-coated PLGA-NPs as compared to unmodified particles.

In vitro & in vivo evaluations of PLGA nanoparticle based combinatorial drug therapy for baclofen and lamotrigine for neuropathic pain management.

AIM: Baclofen and Lamotrigine via PLGA nanoparticles were developed for nose-to-brain delivery for the treatment of Neuropathic pain. METHODS: Nanoparticles were prepared using the modified nano-precipitation method. The prepared NPs were characterised and further in vitro and in vivo studies were performed. RESULTS: The Bcf-Ltg-PLGA-NPs were ∼177.7 nm with >75%(w/w) drugs encapsulated. In vitro dissolution studies suggested zero-order release profiles following the Korsmeyer-Peppas model. In vitro cytotoxicity and staining studies on mammalian cells showed dose dependant cytotoxicity where nanoparticles were significantly less toxic (>95% cell-viability). ELISA studies on RAW-macrophages showed Bcf-Ltg-PLGA-NPs as a potential pro-inflammatory-cytokines inhibitor. In vivo gamma-scintigraphy studies on rats showed intra-nasal administration of 99mTc-Bcf-Ltg-PLGA-NPs showed Cmax 3.6%/g at Tmax = 1.5h with DTE% as 191.23% and DTP% = 38.61% in brain. Pharmacodynamics evaluations on C57BL/6J mice showed a significant reduction in licks/bites during inflammation-induced phase II pain. CONCLUSION: The findings concluded that the combination of these drugs into a single nanoparticle-based formulation has potential for pain management.

Baclofen and Lamotrigine loaded PLGA nanoparticles were prepared with a size of 177.7nm, PDI 0.057 and Zeta Potential −15.8 mVIn vitro cell lines based studies showed dose dependant cytotoxicity and Bcf-Ltg-PLGA-NPs were found to be pro-inflammatory cytokines inhibitorsIn vivo Pharmacokinetic studies showed C_max 3.6%/g at T_max = 1.5 h with Drug Targeting Efficiency 191.23% and Drug Target Organ Transport 38.61% in the brain for prepared nanoparticlesIn vivo pharmacodynamics studies showed a significant reduction in licks/bites during inflammation-induced phase II pain.

A Preliminary Pharmacodynamic Study for the Management of Alzheimer's Disease Using Memantine-Loaded PLGA Nanoparticles.

Alzheimer's disease is becoming a common disorder of the elderly population due to shrinkage of the brain size with age and many other neurological complications. To provide an effective treatment option, memantine-encapsulated polymeric nanoparticles were prepared in the study. The nanoparticles were prepared by using nanoprecipitation followed by homogenization and ultrasonication methods, characterized on the basis of particle size, polydispersity index, and zeta potential. Further, in vitro release profile, cytotoxicity analysis, and Giemsa staining were conducted. To observe the efficacy of nanoparticles in scopolamine-induced Alzheimer models in vivo studies were also carried out. The results showed that nanoparticles were in the nano range with a particle size of 58.04 nm and - 23 mV zeta potential. The in vitro release was also sustained till 24 h with ~ 100% release in selected media phosphate buffer saline, simulated nasal fluid, and artificial cerebrospinal fluid. The cytotoxicity results with ~ 98 to 100% cell viability and no morphological changes through Giemsa staining indicated that nanoparticles were not leading to cell toxicity. The gamma scintigraphy studies showed higher uptake of the drug in the target site through the intranasal route and pharmacodynamic studies indicated that nanoparticles were able to inhibit the spatial memory impairment significantly as compared to the control group. The findings clearly indicated that the developed memantine nanoparticles could act as an alternative approach for the management of Alzheimer's disease.

Advances in Delivery of Chemotherapeutic Agents for Cancer Treatment.

Presently, most of the treatment strategies for cancer are focused on the surgical removal of cancerous tumors, along with physical and chemical treatment such as radiotherapy and chemotherapy, respectively. The primary issue associated with these methods is the inhibition of normal cell growth and serious side effects associated with systemic toxicity. The traditional chemotherapeutics which were delivered systemically were inadequate and had serious dose limiting side effects. Recent advances in the development of chemotherapeutics have simultaneously paved the way for efficient targeted drug delivery. Despite the advances in the field of oncogenic drugs, several limitations remain, such as early blood clearance, acquired resistance against cytotoxic agents, toxicity associated with chemotherapeutics, and site-specific drug delivery. Hence, this review article focuses on the recent scientific advancements made in different types of drug delivery systems, including, organic nanocarriers (polymers, albumins, liposomes, and micelles), inorganic nanocarriers (mesoporous silica nanoparticles, gold nanoparticles, platinum nanoparticles, and carbon nanotubes), aptamers, antibody-drug conjugates, and peptides. These targeted drug delivery approaches offer numerous advantages such as site-specific drug delivery, minimal toxicity, better bioavailability, and an increased overall efficacy of the chemotherapeutics. Graphical abstract.

Synergistic antibacterial and anti-biofilm activity of nisin like bacteriocin with curcumin and cinnamaldehyde against ESBL and MBL producing clinical strains.

Bacteriocins are small peptides that can inhibit the growth of a diverse range of microbes. There is a need to identify bacteriocins that are effective against biofilms of resistant clinical strains. The present study focussed on the efficacy of purified nisin like bacteriocin-GAM217 against extended spectrum ß-lactamase (ESBL) and metallo-beta-lactamase (MBL) producing clinical strains. Bacteriocin-GAM217 when combined with curcumin and cinnamaldehyde, synergistically enhanced antibacterial activity against planktonic and biofilm cultures of Staphylococcus epidermidis and Escherichia coli. Bacteriocin-GAM217 and phytochemical combinations inhibited biofilm formation by >80%, and disrupted the biofilm for selected ESBL and MBL producing clinical strains. The anti-adhesion assay showed that these combinatorial compounds significantly lowered the attachment of bacteria to Vero cells and that they elicited membrane permeability and rapid killing as viewed by confocal microscopy. This study demonstrates that bacteriocin-GAM217 in combination with phytochemicals can be a potential anti-biofilm agent and thus has potential for biomedical applications.

Memantine nanoemulsion: a new approach to treat Alzheimer's disease.

Aim: A nanoemulsion loaded with memantine for intranasal delivery to bypass the blood-brain barrier for the treatment of Alzheimer disease.Method: The nanoemulsion was prepared using homogenisation and ultrasonication methods. The developed nanoemulsion was characterised, in vitro release and antioxidant potential was analysed. The in vivo studies were carried out by radiolabelling the memantine with technetium pertechnetate.Results: The finalised NE showed particle-size of ∼11 nm and percentage transmittance of ∼99%. The in vitro release studies showed 80% drug release in simulated nasal fluid. The nanoemulsion showed 98% cell viability and antioxidative assays confirmed that the encapsulation of memantine in a nanoemulsion sustained its antioxidative potential. Gamma images and biodistribution results also confirmed higher uptake of formulation with %radioactivity of 3.6 ± 0.18%/g at 1.5 h in brains of rats administered intranasally.Conclusion: The developed nanoemulsion could be used as a potential carrier of memantine for a direct nose to brain delivery.

Antibacterial Activity, Cytotoxicity, and the Mechanism of Action of Bacteriocin from Bacillus subtilis GAS101.

OBJECTIVE: The aim of this study was to purify and characterize bacteriocin from the soil isolate Bacillus subtilis GAS101, and to determine its antimicrobial as well as antibiofilm potential. The purified bacteriocin was further analyzed and evaluated for mammalian cell cytotoxicity and the possible mode of action. MATERIAL AND METHODS: Bacteriocin from B. subtilis GAS101 (an animal husbandry soil isolate) was partially purified and checked for antimicrobial and antibiofilm activity against gram-positive and gram-negative bacteria. The molecular weight of bacteriocin was determined using tricine SDS-PAGE gel. The stability of bacteriocin was investigated at various temperatures and pH levels, and its sensitivity towards 8 enzymes and 6 chemicals was determined. Cytotoxicity analysis was performed on a Vero cell line by a tetrazolium dye-based assay. Scanning electron microscopy (SEM) of bacteriocin-treated bacteria was carried out to determine the possible mode of action. RESULTS: Bacteriocin from B. subtilis GAS101 was a potential inhibitor of both the indicator organisms (Staphylococcus epidermidis and Escherichia coli), and had a molecular weight of approximately 6.5 kDa. An in situ gel assay showed a zone of inhibition corresponding to the estimated protein band size. Bacteriocin was stable and showed antibacterial activity in broad ranges of temperature (30-121°C) and pH (2-12). It was sensitive to 4 proteolytic enzymes, which indicated its proteinaceous nature. Bacteriocin showed > 70% cell viability on the mammalian Vero cell line. SEM depicted that the bacteriocin was able to disrupt the bacterial cell membrane as its probable mode of action. CONCLUSION: Thermostable and pH-tolerant bacteriocin from B. subtilis GAS101, of about 6.5 kDa, showed broad-spectrum antimicrobial and antibiofilm activity.

Intravaginal Delivery of Polyphenon 60 and Curcumin Nanoemulsion Gel.

Polyphenon 60 (P60) and curcumin (CUR) were loaded in a single nanoemulsion system and their combined antibacterial action was studied against uropathogenic Escherichia coli. To enhance availability at target organs and to inhibit enzymatic degradation in gastro intestinal tract, vaginal route of administration was explored. P60 + CUR nanoemulsion (NE) was formulated by ultra-sonication and optimized using Box-Behnken design. Optimized NE showed Z-average of 211.2 nm, polydispersity index of 0.343, and zeta potential of -32.7 mV. Optimized P60+ CUR NE was characterized by stability testing and transmission electron microscopy, and it was observed that NE was stable at 4°C for 30 days and monodisperse in nature with particle size of 195-205 nm. P60+ CUR NE was further formulated as gel and characterized by viscosity, growth curve analysis, and in vitro permeation studies. In vitro drug permeation studies in simulated vaginal media showed maximum permeation (84 ± 0.21%) of curcumin within 5 h and (91 ± 0.16%) of P60 within 8 h. Both the drugs maintained sustained permeation for 12 h. To investigate the transport via intravaginal route, gamma scintigraphy and biodistribution study of P60 + CUR NBG was performed on Sprague-Dawley rats using 99mtechnetium pertechnetate for radiolabeling to P60 molecule. Following intravaginal administration, P60 + CUR NBG dispersed in the kidney and urinary bladder with (3.07 ± 0.15) and (3.35 ± 0.45) percentage per gram after 3 h for P60 and CUR, respectively, and remained active for 12 h. Scintigraphy images suggested that the P60 + CUR NBG given by intravaginal route led to effective distribution of actives in urinary tract, and this observation was in agreement with the biodistribution results.

Antimicrobial Peptides as Anti-Infectives against Staphylococcus epidermidis.

Staphylococcus epidermidis has emerged as the main causative agent for graft-related and nosocomial infections. Rampant use of antibiotics and biofilm formed by the organism results in poor penetration of the drug and further aggravates the antibiotic resistance, emphasizing an urgent need to explore alternative treatment modalities. Antimicrobial peptides (AMPs), produced as effector molecules of the innate immunity of living organisms, have therapeutic potential that can be used to inhibit the growth of microbes. In addition, the susceptibility of a microbe to become resistant to an AMP is relatively low. The AMPs are amphipathic peptides of 12-100 residues, which have broad-spectrum activity against microbes. There are scattered reports of AMPs listed against S. epidermidis and there is an urgent need to systematically study the AMPs. Various natural AMPs as well as synthetic peptides have been investigated against S. epidermidis. These peptides have been shown to inhibit both planktonic culture and S. epidermidis biofilm effectively. The multiple modes of action in killing the organism minimize the chances for the development of resistance. This review focused on various natural and synthetic peptides that demonstrate activity against S. epidermidis.

Nose-To-Brain Delivery of PLGA-Diazepam Nanoparticles.

The objective of the present investigation was to optimize diazepam (Dzp)-loaded poly(lactic-co-glycolic acid) nanoparticles (NP) to achieve delivery in the brain through intranasal administration. Dzp nanoparticles (DNP) were formulated by nanoprecipitation and optimized using Box-Behnken design. The influence of various independent process variables (polymer, surfactant, aqueous to organic (w/o) phase ratio, and drug) on resulting properties of DNP (z-average and drug entrapment) was investigated. Developed DNP showed z-average 148-337 d.nm, polydispersity index 0.04-0.45, drug entrapment 69-92%, and zeta potential in the range of -15 to -29.24 mV. Optimized DNP were further analyzed by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), ex-vivo drug release, and in-vitro cytotoxicity. Ex-vivo drug release study via sheep nasal mucosa from DNP showed a controlled release of 64.4% for 24 h. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay performed on Vero cell line showed less toxicity for DNP as compared to Dzp suspension (DS). Gamma scintigraphy and biodistribution study of DNP and DS was performed on Sprague-Dawley rats using technetium-99m-labeled ((99m)Tc) Dzp formulations to investigate the nose-to-brain drug delivery pathway. Brain/blood uptake ratios, drug targeting efficiency, and direct nose-to-brain transport were found to be 1.23-1.45, 258, and 61% for (99m)Tc-DNP (i.n) compared to (99m)Tc-DS (i.n) (0.38-1.06, 125, and 1%). Scintigraphy images showed uptake of Dzp from nose-to-brain, and this observation was in agreement with the biodistribution results. These results suggest that the developed poly(D,L-lactide-co-glycolide) (PLGA) NP could serve as a potential carrier of Dzp for nose-to-brain delivery in outpatient management of status epilepticus.

Pseudomonas aeruginosa biofilm: potential therapeutic targets.

Pseudomonas aeruginosa is a gram-negative pathogen that has become an important cause of infection, especially in patients with compromised host defense mechanisms. It is frequently related to nosocomial infections such as pneumonia, urinary tract infections (UTIs) and bacteremia. The biofilm formed by the bacteria allows it to adhere to any surface, living or non-living and thus Pseudomonal infections can involve any part of the body. Further, the adaptive and genetic changes of the micro-organisms within the biofilm make them resistant to all known antimicrobial agents making the Pseudomonal infections complicated and life threatening. Pel, Psl and Alg operons present in P. aeruginosa are responsible for the biosynthesis of extracellular polysaccharide which plays an important role in cell-cell and cell-surface interactions during biofilm formation. Understanding the bacterial virulence which depends on a large number of cell-associated and extracellular factors is essential to know the potential drug targets for future studies. Current novel methods like small molecule based inhibitors, phytochemicals, bacteriophage therapy, photodynamic therapy, antimicrobial peptides, monoclonal antibodies and nanoparticles to curtail the biofilm formed by P. aeruginosa are being discussed in this review.

Combinatorial antimicrobial effect of curcumin with selected phytochemicals on Staphylococcus epidermidis.

Staphylococcus epidermidis is reported to be the main causative agent of nosocomial infections. It has become increasingly difficult to treat this micro-organism because of the emergence of new antibiotic-resistant strains and its ability to form biofilm on medical associated devices. Phytochemicals acting in synergy are effective in killing the micro-organisms by lowering the doses, and synergistic compounds evade the development of resistance due to different mechanism of action. This study aims to determine the synergistic antimicrobial potential of curcumin with cinnamaldehyde, eugenol, and ellagic acid against S. epidermidis. Curcumin with ellagic acid as well as eugenol were found to have additive antimicrobial effect, whereas, in combination, curcumin and cinnamaldehyde were found to have synergistic effect against S. epidermidis (fractional inhibitory concentration index (FICI) = 0.5). Synergy between curcumin and cinnamaldehyde was established by time-kill kinetics and was further evaluated for antibiofilm activity. The dose required to inhibit biofilm formation was reduced to half than that needed to inhibit its planktonic culture (minimal inhibitory concentration (MIC) of curcumin = 3.12 µg/ml; MIC of cinnamaldehyde = 15.62 µg/ml; FICI = 0.248). Both curcumin and cinnamaldehyde disrupted the bacterial membrane for killing the bacteria as determined by permeability studies on Escherichia coli ML-35p.

Nanocarrier-Based Drug Delivery to Brain: Interventions of Surface Modification.

Brain disorders are a prevalent and rapidly growing problem in the medical field as they adversely affect the quality of life of a human. With an increase in life expectancy, it has been reported that diseases like Alzheimer's, Parkinson's, stroke and brain tumors, along with neuropsychological disorders, are also being reported at an alarmingly high rate. Despite various therapeutic methods for treating brain disorders, drug delivery to the brain has been challenging because of a very complex Blood Brain Barrier, which precludes most drugs from entering the brain in effective concentrations. Nano-carrier-based drug delivery systems have been reported widely by researchers to overcome this barrier layer. These systems due to their small size, offer numerous advantages; however, their short residence time in the body owing to opsonization hinders their success in vivo. This review article focuses on the various aspects of modifying the surfaces of these nano-carriers with polymers, surfactants, protein, antibodies, cell-penetrating peptides, integrin binding peptides and glycoproteins such as transferrin & lactoferrin leading to enhanced residence time, desirable characteristics such as the ability to cross the blood-brain barrier (BBB), increased bioavailability in regions of the brain and targeted drug delivery.

Evaluation of Enhanced Cytotoxicity Effect of Repurposed Drug Simvastatin/ Thymoquinone Combination against Breast Cancer Cell Line.

INTRODUCTION: The repurposing of drugs for their anticancer potential is gaining a lot of importance in drug discovery. AIMS: The present study aims to explore the potential of Simvastatin (SIM), a drug used in the treatment of high cholesterol, and thymoquinone (Nigella Sativa) (THY) for its anti-cancer activity on breast cancer cell lines. Thymoquinone is reported to have many potential medicinal properties exhibiting antioxidant, antiinflammatory, anti-cancer, and activities like tissue growth and division, hormone regulation, immune response and development, and cell signaling. METHODS: In this analysis, we explored the inhibitory effects of the combination of simvastatin ad thymoquinone on two breast cancer cell lines viz MCF-7 and MDA-MB-231 cells. The combined effect of simvastatin ad thymoquinone on cell viability, colony formation, cell migration, and orientation of more programmed cell death in vitro was studied. Cell cycle arrest in the G2/M phase was concomitant with the combined effect of SIM and THY persuading apoptosis and generating reactive oxygen species (ROS). RESULTS: The cell cycle arrest in combined treatment was 8.1% on MCF-7 cells and 3.8 % for MDA-MB-231 cells an increased apoptosis was observed when cells were treated in combination which was about 76.20% and 58.15 % respectively for MCF-7 and MDA-MB-231 cells. CONCLUSION: It was concluded that the combined effect of simvastatin and thymoquinone stimulates apoptosis in breast cancer cells.

Nose to Brain Delivery of Transferrin conjugated PLGA nanoparticles for clonidine.

The present work focuses on the development of surface modified transferrin PLGA nanoparticles loaded with clonidine for nose to brain delivery. The CLD-Tf-PLGA-NPs were developed using double emulsification, followed by solvent evaporation and characterization. Particle size, PDI and Zeta potential of the nanoparticles was 199.5 ± 1.36 nm, 0.291, -17.4 ± 6.29 mV respectively with EE% 86.2 ± 2.12 %, and DL%, 7.8 ± 0.48 %. TEM, SEM and FTIR analysis were carried out to confirm the size and transferrin coating over the surface of nanoparticles. In-vitro drug release profile were studied in PBS (pH 7.4) and SNF (pH 5.5) for 72 h and highest release was observed in PBS 89.54 ± 3.17 %. Cellular assays were conducted on Neuro-2a cells to check the cytotoxicity and uptake of Tf-modified PLGA nanoparticles and the cell viability% was obtained to be 61.85 ± 4.48 % even at maximum concentration (40Cmax) with uptake of approximately 97 %. Histopathological studies were also performed to identify the cytotoxicity on nasal epithelium along with in-vivo biodistribution and pharmacodynamics studies to assess the concentration of drug in the mice brain and behavioural responses after intranasal delivery of surface modified nanoparticles. The results showed significant increase in concentration of drug in brain and behavioural improvements in mice (p < 0.05).

Advances in microneedle-based transdermal delivery for drugs and peptides.

Transdermal drug delivery is a viable and clinically proven route of administration. This route specifically requires overcoming the mechanical barrier provided by the Stratum Corneum of epidermis and vascular and nervous networks within the dermis. First-generation Transdermal patches and second-generation iontophoretic patches have been translated into commercial clinical products successfully. The current review reports different studies that aim to enhance the transdermal delivery of biopharmaceutical using microneedles and their effect on drug delivery. Microneedles (MN) are the micron-scale hybrid between transdermal patches and hypodermic syringes. Microneedles are tested and proven to show better delivery of the drugs, overcoming the drawbacks of hypodermic syringes. Multiple microneedles designs have been fabricated i.e. solid, coated, hollow, and polymer microneedles. Hollow microneedles are shorter in length but similar to hypodermic needles and have pore for infusion of liquid formulation of the drug. Solid microneedles a patch is applied after creating a hole in the skin; Drugs are coated on the surface of Coated microneedles; Polymer microneedles can be of different types like dissolving, non-dissolving or hydrogel-forming made up of polymers. Various advantages and limitations associated with the use of these techniques are discussed. Delivery of peptide and protein molecules with microneedles represents a significant opportunity for a better clinical outcome and hence value creation compared to standard injectable routes of administration. The advancement in various formulation and microfabrication techniques are currently being focused to aid the delivery of protein drugs via microneedles. The most recent advances and limitations in Microneedles -mediated protein and peptide delivery were discussed.

Amelioration of oxidative stress utilizing nanoemulsion loaded with bromocriptine and glutathione for the management of Parkinson's disease.

Parkinson's disease (PD) is triggered by the formation of free radicals in dopaminergic neurons, which results in oxidative stress-induced neurodegeneration. The objective of the work was to relieve oxidative stress by employing intranasal delivery of Bromocriptine Mesylate (BRM) and Glutathione (GSH) loaded nanoemulsion for the better management of PD. The depth of permeation of the nanoemulsion was assessed through confocal laser scanning microscopy (CLSM) which revealed higher nanoemulsion permeation in contrast to suspension. Biocompatibility of nanoemulsion was confirmed by nasal cilio toxicity study. The DPPH study showed that the nanoemulsion had significant antioxidant activity. Biochemical estimation studies in Wistar rats were carried out in order to determine the effect of nanoemulsion on oxidative stress. The levels of GSH, superoxide dismutase (SOD), and catalase (CAT) were significantly enhanced; and the level of thiobarbituric acid reactive substances (TBARS) was significantly reduced after the intranasal administration of nanoemulsion in the haloperidol-induced model of PD. Furthermore, the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were also determined which reduced significantly after the administration of nanoemulsion. The oxidative stress levels were lowered with nanoemulsion, showing the combined antioxidant capability of BRM and GSH. The neuroprotective effect of the prepared nanoemulsion was confirmed by histopathological studies. Pharmacokinetic study revealed a higher concentration of BRM and GSH in the brain of Wistar rats after intranasal administration of nanoemulsion with a higher Brain/Plasma ratio. A higher value of AUC(0-8) of nanoemulsion in the brain after intranasal administration revealed that BRM and GSH remained in the brain for a longer period due to sustained release from nanoemulsion. According to the findings, BRM and GSH loaded nanoemulsion has the potential to provide a combined and synergistic anti-oxidant effect for efficient management of PD.

Anti-Cancer Potential of Some Commonly Used Drugs.

Cancer is a global concern leading to millions of deaths every year. A declining trend in new drug discovery and development is becoming one of the major issues among the pharmaceutical, biotechnology industries and regulatory agencies. New drug development is proven to be a very lengthy and a costly process. Launch of a new drug takes 8-12 years and huge investments. Success rate in oncology therapeutics is also low due to toxicities at the pre-clinical and clinical trials level. Many oncological drugs get rejected at very promising stage showing adverse reactions on healthy cells. Thus, exploring new therapeutic benefits of the existing, shelved drugs for their anti-cancerous action could result in a therapeutic approach preventing the toxicities which occurs during clinical trials. Drug repurposing has the potential to overcome the challenges faced via conventional way of drug discovery and is becoming an area of interest for researchers and scientists. Although very few in vivo studies are conducted to prove the anti-cancerous activity of the drugs. Insufficient in vivo animal studies and lack of human clinical trials are the lacuna in the field of drug repurposing. This review focuses on the aspect of drug repurposing for cancer therapeutics. There are various studies which show that drugs approved for clinical indications other than cancer have shown promising anti-cancer activities. Some of the commonly used drugs like Benzodiazepines (Diazepam, Midzolam), Antidepressants (Imipramine, Clomipramine, and Citalopram), Antiepileptic (Valporic acid, Phenytoin), Anti diabetics (metformin) etc., have been reported to show potential activity against the cancerous cells.

Neuropsychological Disorders and their Nanocarriers.

Neuropsychological disorders are now growing rapidly worldwide among the people of diverse backgrounds irrespective of age, gender, and geographical region. Such disorders not only disturb the normal life and functionality of an individual but also impact the social relationships of the patient and the people associated with them, and if not treated in time, it may also result in mortality in severe conditions. Various antipsychotic drugs have been developed but their use is often limited by issues related to effective drug delivery at the site of action i.e. brain, mainly because of the blood-brain barrier. To resolve these issues, researchers and scientists have been working to develop a more effective drug delivery system where drugs can cross the blood-brain barrier and reach the brain in more effective concentrations. Drugs have been modified and formulated into nano-carriers and experimental studies for efficient and targeted delivery of drugs have been conducted. This review focuses on certain common neuropsychological diseases and their nanocarriers developed for drug delivery in the brain and are discussed with a brief description of various experimental in vitro and in vivo studies. This review also focuses on the intranasal route for the delivery of antipsychotic drugs and constraints faced due to the blood-brain barrier by the drugs.