Application of Box-Behnken Design in the Optimization and Preparation of Salicylic Acid Nanopowder using Solvent-Free Green Mechanochemical Approach.

Background: One of the imperative progressions within the pharmaceutical industry, especially drugs, is the expanded utilization of materials in order to enhance its dissolution, solubility and bioavailability. Planetary ball monomill approach can be the latest entrant to Green nanotechnology - being solvent-free, eco-friendly, cost-effective, and sustainable particle size reduction approach. Objectives: Salicylic acid nanopowder (SA-NP) was aimed to be prepared using planetary ball monomill by dry milling technique to enhance its solubility and bioavailability. Methods: Various milling parameters such as milling speed, milling time and number of balls was varied and their effect on dependent responses including size (nm) and polydispersity indices (PDI) were evaluated using a 3-Factorial-3-Level Box-Behnken statistical design. Particle size and PDI analysis was performed using light scattering technique. Results: The particle size of salicylic acid obtained by optimizing the dry milling parameters was Z-Average (d.nm): 776.3 nm and PDI: 0.600 up to Z-Average (d. nm): 205.0 nm and PDI: 0.383. Conclusions: Dry milling can be used for the preparation of nanopowders of drug candidates with poor water-solubility issues. Present day medications have nano-scaled active ingredients which are rapidly absorbed by the human body as compared to the conventional ones. Enlarged surface area increases the solubility of the drug, thereby improves its bioavailability.

Role of cinnamon oil against acetaminophen overdose induced neurological aberrations through brain stress and cytokine upregulation in rat brain.

Acetaminophen (APAP) is a well-known antipyretic and analgesic medicine. It is safe at therapeutic suggested level while overdose initiates oxidative stress and inflammation mediated neurochemical alteration in the brain. The aim of this study was to investigate the role of cinnamon oil (CO), which possesses potent antioxidant and anti-inflammatory activities against an overdose of APAP that induced oxidative stress and inflammation in male albino rats. APAP treated rats showed significant elevation of thiobarbituric acid-reactive substances (TBARS) and decreased level of GSH in brain tissue, which is recognized as a biomarker of oxidative stress. Antioxidant enzymes GPx, GR, SOD, and CAT activity was depleted in APAP group along with neurotoxicity biomarkers such as Na+-K+-ATPase and increased activity of acetylcholinesterase (AchE), monoamine oxidase (MAO), and upregulated pro-inflammatory cytokine was observed. CO significantly protected the diminished activity of the antioxidant enzyme and suppressed the upregulated cytokines in brain tissue. CO also attenuated the activity of neurotoxicity biomarker enzyme, decreased TBARS content, and an increased level of GSH. The present findings perceptibly confirmed that the nutraceutical property of CO ameliorates APAP induced oxidative stress and inflammation. Therefore, our findings suggested that CO could be an alternative nutraceutical substitute in APAP overdose poisoning.

Preparation, Characterization, and Anti-Cancer Activity of Nanostructured Lipid Carriers Containing Imatinib.

Breast cancer is the most widespread malignancy in women worldwide. Nanostructured lipid carriers (NLCs) have proven effective in the treatment of cancer. NLCs loaded with imatinib (IMA) (NANIMA) were prepared and evaluated for their in vitro efficacy in MCF-7 breast cancer cells. The hot homogenization method was used for the preparation of NANIMAs. An aqueous solution of surfactants (hot) was mixed with a molten mixture of stearic acid and sesame oil (hot) under homogenization. The prepared NANIMAs were characterized and evaluated for size, polydispersity index, zeta potential, encapsulation efficiency, release studies, stability studies, and MTT assay (cytotoxicity studies). The optimized NANIMAs revealed a particle size of 104.63 ± 9.55 d.nm, PdI of 0.227 ± 0.06, and EE of 99.79 ± 0.03. All of the NANIMAs revealed slow and sustained release behavior. The surfactants used in the preparation of the NANIMAs exhibited their effects on particle size, zeta potential, encapsulation efficiency, stability studies, and release studies. The cytotoxicity studies unveiled an 8.75 times increase in cytotoxicity for the optimized NANIMAs (IC50 = 6 µM) when compared to IMA alone (IC50 = 52.5 µM) on MCF-7 breast cancer cells. In the future, NLCs containing IMA will possibly be employed to cure breast cancer. A small amount of IMA loaded into the NLCs will be better than IMA alone for the treatment of breast cancer. Moreover, patients will likely exhibit less adverse effects than in the case of IMA alone. Consequently, NANIMAs could prove to be useful for effective breast cancer treatment.

Ganoderma lucidum: A potential source to surmount viral infections through ß-glucans immunomodulatory and triterpenoids antiviral properties.

Ganoderma lucidum (G. lucidum) polysaccharides and triterpenoids are the major bioactive compounds and have been used as traditional medicine for ancient times. Massive demands of G. lucidum have fascinated the researchers towards its application as functional food, nutraceutical and modern medicine owing to wide range of application in various diseases include immunomodulators, anticancer, antiviral, antioxidant, cardioprotective, hepatoprotective. G. lucidum polysaccharides exhibit immunomodulatory properties through boosting the action of antigen-presenting cells, mononuclear phagocyte system, along with humoral and cellular immunity. ß-Glucans isolated from G. lucidum are anticipated to produce an immune response through pathogen associated molecular patterns (PAMPs). ß-Glucans after binding with dectin-1 receptor present on different cells include macrophages, monocytes, dendritic cells and neutrophils produce signal transduction that lead to trigger the mitogen-activated protein kinases (MAPKs), T cells and Nuclear factor-κB (NF-κB) that refer to cytokines production and contributing to immune response. While triterpenoids produce antiviral effects through inhibiting various enzymes like neuraminidase, HIV-protease, DENV2 NS2B-NS3 protease and HSV multiplication. Polysaccharides and triterpenoids adjunct to other drugs exhibit potential action in prevention and treatment of various diseases. Immunomodulators and antiviral properties of this mushroom could be a potential source to overcome this current pandemic outbreak.

Formulation and evaluation of injectable dextran sulfate sodium nanoparticles as a potent antibacterial agent.

The purpose of this study was to develop a novel nano antibacterial formulation of dextran sulfate sodium polymer. The dextran sulfate sodium (DSS) nanoparticles were formulated with gelation technique. The nanoparticles exhibited significant physicochemical and effective antibacterial properties, with zeta potential of - 35.2 mV, particle size of 69.3 z d nm, polydispersity index of 0.6, and percentage polydispersity of 77.8. The DSS nanoparticles were stable up to 102 °C. Differential scanning calorimetry revealed an endothermic peak at 165.77 °C in 12.46 min, while XRD analysis at 2θ depicted various peaks at 21.56°, 33.37°, 38.73°, 47.17°, 52.96°, and 58.42°, indicating discrete nanoparticle formation. Antibacterial studies showed that the DSS nanoparticles were effective against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentrations of DSS nanoparticles for Bacillus subtilis (B. subtilis), Staphylococcus aureus (S. aureus), Streptococcus pyogenes (S. pyogenes), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae) and Proteus vulgaris (P. vulgaris) were 150, 200, 250, 150, 200, 250, 250 µg/mL, respectively. The antibacterial effects of DSS nanoparticles were in the order E. coli (26 ± 1.2 mm) at 150 µg/mL > S. pyogenes (24.6 ± 0.8 mm) at 250 µg/mL > B. subtilis (23.5 ± 2 mm) at 150 µg/mL > K. pneumoniae (22 ± 2 mm) at 250 µg/mL > P. aeruginosa (21.8 ± 1 mm) at 200 µg/mL > S. aureus (20.8 ± 1 mm) at 200 µg/mL > P. vulgaris (20.5 ± 0.9 mm) at 250 µg/mL. These results demonstrate the antibacterial potency of DSS injectable nanoparticles.

Pharmacoscintigraphic evaluation of potential of lipid nanocarriers for nose-to-brain delivery of antidepressant drug.

Efficacy of antidepressants relies upon their continued presence at the site of action (brain) over a prolonged period of time. The BBB restricts the access of antidepressants to the brain on oral as well as intravenous administration. Direct delivery (by-passing the BBB) of antidepressant drugs can increase the CSF concentration with concomitant reduction in dose and side effects. Intranasal administration of nanostructured lipid carriers (NLC) containing antidepressant drug circumvent the BBB and maintain the prolonged release at the site of action. The aim of the present study was to evaluate the enhancement in brain uptake of NLC containing duloxetine (DLX) after intranasal administration. Duloxetine loaded NLC (DLX-NLC) was evaluated pharmacoscintigraphically for drug targeting potential (DTP), drug targeting efficiency (DTE) and biodistribution studies in different organs including brain. The radiolabeling efficiency of DLX and DLX-NLC was found to be 98.41 ± 0.96 and 98.87 ± 0.82 after 30 min, respectively. The biodistribution studies exhibited higher percentage of radioactivity/g for DLX-NLC formulations in brain as compared with the DLX. The higher DTP (86.80%) and DTE (757.74%) suggested that DLX-NLC formulation has a better brain targeting efficiency than DLX solution (DTP=65.12%; DTE=287.34%) when administered intranasally. Moreover, the intranasal administration exhibited about 8-times higher concentration of DLX in brain when compared with the intravenous administration of DLX solution. The intranasal NLC containing DLX can be employed as an effective method for the treatment of depression.

Intranasal infusion of nanostructured lipid carriers (NLC) containing CNS acting drug and estimation in brain and blood.

The present study was aimed to evaluate the nanostrucured lipid carriers (NLC) containing duloxetine (DLX-NLC) for intranasal infusion through the nasal cavity of rat. The in vivo nasal infusion studies were performed using Wistar rats and the amount of DLX permeated and its amount in brain and blood was estimated. The effects on absorption rate and type of drug delivery systems (nanocarriers and drug solution) for nose to brain/blood permeation were assessed. DLX was found to be permeated from the nasal cavity into the body of rat and the permeated amount was found to be more in case of DLX-NLC. Approximately 2.5-times better permeation was exhibited by DLX-NLC than DLX-solution. Appreciable amount of DLX was estimated in blood and brain and the estimated amount was higher in case of DLX-NLC. Thus the administration of NLC containing DLX through intranasal route was found to be potential method for the delivery of DLX for the treatment of depression.

Intranasal administration of nanostructured lipid carriers containing CNS acting drug: pharmacodynamic studies and estimation in blood and brain.

The present study was aimed to investigate and compare the efficacy of duloxetine (DLX) loaded nanostructured lipid carriers (NLC) with DLX solution pharmacodynamically following intranasal administration. The study was further conducted to estimate DLX concentration in brain and blood. DLX was administered to albino Wistar rats either intranasally or orally in solution form (DLX solution) or encapsulated in NLC (DLX-NLC). These were evaluated in-vivo for pharmacodynamic studies for depression by forced swimming test and locomotor activity test. Intranasal DLX-NLC treatment exhibited improved behavioural analysis results (swimming, climbing, and immobility) than the DLX solution after 24 h of study. Furthermore, DLX-NLC significantly increased the total swimming and climbing time when compared with control and significantly reduced the immobility period. The intranasal DLX-NLC demonstrated improved locomotor activity when compared with DLX solution. Amount of DLX was quantified in blood and brain after the forced swimming test. The intranasal DLX-NLC demonstrated higher concentration in brain compared with DLX solution. Thus, intranasal DLX-NLC was found to be a promising formulation for the treatment of depression.

Strategy for effective brain drug delivery.

Blood-brain barrier (BBB) together with enzymes restricts the entry of substances for maintaining the internal milieu of the brain. Because of the presence of multiple endogenous transporters, BBB allows a selective entry of nutrients and minerals across it and limits the entry of foreign substances like drugs as well as neuropharmaceutical agents. This makes the CNS treatment ineffective. The conventional drug delivery systems which release drug into general circulation fail to deliver drugs effectively to brain and is therefore not very useful in treating certain diseases that affect CNS including Alzheimer's disease, dementia, Parkinson's disease, mood disorder, AIDS, viral and bacterial meningitis. Therefore there is a need to develop and design approaches which specifically target to brain in a better and effective way. The present review enlightens about several novel approaches including nanotechnology based approach like nanoparticles, liposomes, antibody mediated delivery approach and application of genomics in brain drug targeting that would give an insight to the researchers, academia and industrialists.

Pharmacodynamics of a losartan transdermal system for the treatment of hypertension.

AIMS: Transdermal therapeutic systems were developed using the polymers, Eudragit E 100 and polyvinyl pyrrolidone VA 64 in a film casting assembly. The medicated films were evaluated for physical properties, in vitro drug release studies, in vitro skin permeation studies, and pharmacodynamic studies. RESULTS: The physical parameters were found to be very satisfactory with high drug content (>99%). The in vitro drug release studies were performed using paddle-over-disc assembly specified in USP XXIII. The pharmacodynamic studies were carried out using tail cuff method in Wistar albino rats. Hypertension was induced by methyl prednisolone acetate subcutaneously for 2 weeks. The developed matrix patch was found to decrease the blood pressure (25.42% reduction in mean systolic blood pressure of rats) significantly (P < 0.001) in proximity of the normal value and it was maintained for 24 hours. CONCLUSION: It can be concluded that the developed transdermal matrix patch holds promise for the management of hypertension that needs to be validated by clinical trials.