scholarly journals Mucoadhesive, Thermoreversible Hydrogel, Containing Tetracaine-Loaded Nanostructured Lipid Carriers for Topical, Intranasal Needle-Free Anesthesia

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1760
Author(s):  
Giovana Maria Fioramonti Calixto ◽  
Bruno Vilela Muniz ◽  
Simone R. Castro ◽  
Jaiza Samara Macena de Araujo ◽  
Klinger de Souza Amorim ◽  
...  
Keyword(s):  
Hybrid System ◽  
Neuroblastoma Cells ◽  
Fold Increase ◽  
Nanostructured Lipid Carriers ◽  
Poloxamer 407 ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Hybrid Hydrogel ◽  
Thermoreversible Hydrogel

Recent advances have been reported for needle-free local anesthesia in maxillary teeth by administering a nasal spray of tetracaine (TTC) and oxymetazoline, without causing pain, fear, and stress. This work aimed to assess whether a TTC-loaded hybrid system could reduce cytotoxicity, promote sustained permeation, and increase the anesthetic efficacy of TTC for safe, effective, painless, and prolonged analgesia of the maxillary teeth in dental procedures. The hybrid system based on TTC (4%) encapsulated in nanostructured lipid carriers (NLC) and incorporated into a thermoreversible hydrogel of poloxamer 407 (TTCNLC-HG4%) displayed desirable rheological, mechanical, and mucoadhesive properties for topical application in the nasal cavity. Compared to control formulations, the use of TTCNLC-HG4% slowed in vitro permeation of the anesthetic across the nasal mucosa, maintained cytotoxicity against neuroblastoma cells, and provided a three-fold increase in analgesia duration, as observed using the tail-flick test in mice. The results obtained here open up perspectives for future clinical evaluation of the thermoreversible hybrid hydrogel, which contains TTC-loaded NLC, with the aim of creating an effective, topical, intranasal, needle-free anesthesia for use in dentistry.

Nanostructured Lipid Carriers for Intranasal Administration of Olanzapine in the management of Schizophrenia

2021 ◽  
Vol 14 ◽  
Author(s):  
Sarbjot Kaur ◽  
Ujjwal Nautiyal ◽  
Pooja A. Chawla ◽  
Viney Chawla
Keyword(s):  
Drug Delivery ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Nanostructured Lipid Carriers ◽  
Polydispersity Index ◽  
Poloxamer 407 ◽  
Ex Vivo Permeation ◽  
Permeation Studies ◽  
Vitro Release

Background: Background: Olanzapine belongs to a new class of dual spectrum antipsychotic agents. It is known to show promise in managing both the positive and negative symptoms of schizophrenia. Drug delivery systems based on nanostructured lipid carriers (NLC) are expected to provide rapid nose-to-brain transport of this drug and improved distribution into and within the brain. Objective: The present study deals with the preparation and evaluation of olanzapine loaded NLC via the intranasal route for schizophrenia. Methods: Olanzapine-NLC were formulated through the solvent injection method using isopropyl alcohol as the solvent, stearic acid as solid lipid, and oleic acid as liquid lipid, chitosan as a coating agent, and Poloxamer 407 as a surfactant. NLC were characterized for particle size, polydispersity index, entrapment efficiency, pH, viscosity, X-ray diffraction studies, in-vitro mucoadhesion study, in- vitro release and ex-vivo permeation studies. The shape and surface morphology of the prepared NLC was determined through transmission electron microscopy. To detect the interaction of the drug with carriers, compatibility studies were also carried out. Results: Average size and polydispersity index of developed formulation S6 was 227.0±6.3 nm and 0.460 respectively. The encapsulation efficiency of formulation S6 was found to be 87.25 %. The pH, viscosity, in-vitro mucoadhesion study, and in- vitro release of optimized olanzapine loaded NLC were recorded as 5.7 ± 0.05, 78 centipoise, 15±2 min, and 91.96 % respectively. In ex-vivo permeation studies, the percent drug permeated after 210 min was found to be 84.03%. Conclusion: These results reveal potential application of novel olanzapine-NLC in intranasal drug delivery system for treatment of schizophrenia.

Prolonged Anti-Inflammatory Activity of Topical Melatonin by Niosomal Encapsulation

2014 ◽  
Vol 902 ◽  
pp. 70-75 ◽  
Author(s):  
Aroonsri Priprem ◽  
Vassana Netweera ◽  
Pramote Mahakunakorn ◽  
Nutjaree Pratheepawanit Johns ◽  
Jeffrey Roy Johns
Keyword(s):  
Skin Permeation ◽  
Entrapment Efficiency ◽  
Rapid Decline ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Topical Gel ◽  
Anti Inflammatory ◽  
Average Size

Melatonin, encapsulated and non-encapsulated, in a topical gel, was comparatively investigated for its in vitro permeation and in vivo anti-inflammatory properties. An average size of the melatonin-encapsulated niosomes of 197 nm with a zeta potential of-78.8 mV and an entrapment efficiency of 92.7% was incorporated into a gel base. In vitro skin permeation of the same gel base incorporated with non-encapsulated melatonin or melatonin niosomes at 5% was comparatively evaluated through porcine skin using Franz diffusion cells and analyzed by spectroflurometry at λex 278 and λem 348 nm. From the same gel base, the permeation rate of non-encapsulated melatonin was about 2.5 times greater than that of melatonin-encapsulated niosomes. In comparison to piroxicam gel and hydrocortisone cream used as the positive controls, topical applications of melatonin and melatonin niosome gels tested in croton oil-induced ear edema in mice suggested that its anti-inflammatory activities were prolonged by the niosomal encapsulation. Similarly, analgesic effect of melatonin was prolonged by niosomal encapsulation using tail flick test in mice. Therefore, its immediate permeation through the skin was retarded by niosomal encapsulation which could also prolong its rapid decline in exerting anti-inflammatory and analgesic activities in vivo.

1-(2,4-Dibromophenyl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one

2017 ◽  
Vol 126 (5) ◽  
pp. 952-966 ◽  
Author(s):  
Po-Kuan Chao ◽  
Shau-Hua Ueng ◽  
Li-Chin Ou ◽  
Teng-Kuang Yeh ◽  
Wan-Ting Chang ◽  
...  
Keyword(s):  
Radioligand Binding ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
In Vivo Studies ◽  
Tail Flick ◽  
Gastrointestinal Dysfunction ◽  
Meal Test ◽  
Tail Flick Test ◽  
Tail Clip

Abstract Background The authors investigated the pharmacology and signaling pathways of the opioid receptors modulated by compound 1, 1-(2,4-dibromophenyl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one. Methods In vitro studies of compound 1 were assessed by using a radioligand-binding assay (n = 3), a cyclic adenosine monophosphate assay (n = 3), a β-arrestin assay (n = 3), an internalization assay (n = 3), and an immunohistochemistry (n = 8). In vivo studies of compound 1 were characterized using a tail-flick test (n = 5 to 6), tail-clip test (n = 7), von Frey hair test (n = 5), and charcoal meal test (n = 5). Results Compound 1 elicited robust effects in μ-opioid (mean ± SD; binding affinity: 15 ± 2 nM; cyclic adenosine monophosphate assay: 24 ± 6 nM), δ-opioid (82 ± 7 nM; 1.9 ± 0.1 μM), and κ-opioid (76 ± 9 nM; 1.4 ± 0.5 μM) receptor–expressing cells. Compound 1 acts as a full agonist of β-arrestin-2 recruitment in μ-opioid (1.1 ± 0.3 μM) and δ-opioid (9.7 ± 1.9 μM) receptor–expressing cells. Compound 1 caused less gastrointestinal dysfunction (charcoal meal test: morphine: 82 ± 5%; compound 1: 42 ± 5%) as well as better antinociception in mechanical pain hypersensitivity (tail-clip test: morphine: 10 ± 3 s; compound 1: 19 ± 1 s) and in cancer-induced pain (von Frey hair test: morphine: 0.1 ± 0.1 g; compound 1: 0.3 ± 0.1 g) than morphine at equi-antinociceptive doses. Conclusions Compound 1 produced antinociception with less gastrointestinal dysfunction than morphine.

scholarly journals Pre-treatment Effect of Kombucha Tea on Analgesia and Inflammation in Male Rat

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Zahra Rabiei ◽  
Zahra Lorigooini ◽  
Fatemeh Firuzi ◽  
Mohammad Rahimi-Madiseh
Keyword(s):  
Acetic Acid ◽  
Pain Tolerance ◽  
Male Rat ◽  
Control Group ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Analgesic Effects ◽  
Kombucha Tea ◽  
Anti Inflammatory

Background: The use of natural compounds in relieving pain has been commonplace since ancient times and their use is currently increasing. Objectives: Given that analgesic and anti-inflammatory effects of Kombucha have not been studied, this study was designed to examine these effects in vitro. Methods: In this experimental study, rats were divided into four groups. The control group received normal saline i.p in the same amount of the drug. The other groups received Kombucha tea i.p at 250, 500, and 1000 mg/kg. Tail-flick and acetic acid tests were used to evaluate the analgesic effects of Kombucha tea and the xylene-induced ear inflammation test to evaluate the anti-inflammatory effects of Kombucha tea. Results: Kombucha tea at three doses 250, 500, and 1000 mg/kg significantly reduced the number of writhings in the acetic acid test. Kombucha tea at 1000 mg/kg significantly increased pain tolerance in the tail-flick test. Kombucha tea at 250 and 500 mg/kg could significantly reduce inflammation in the rat’s ear. Conclusions: The results of this study indicate that Kombucha has analgesic effects in rats and can be considered in future treatments.

scholarly journals Anastrozole Loaded Nanostructured Lipid Carriers : Preparation and Evaluation

2021 ◽  
Vol 30 (2) ◽  
pp. 185-195
Author(s):  
Alaa Abdul-Jabbar Hashim ◽  
Nawal A. Rajab
Keyword(s):  
Hot Flashes ◽  
Entrapment Efficiency ◽  
Tween 80 ◽  
Nanostructured Lipid Carriers ◽  
Poloxamer 407 ◽  
Fourth Generation ◽  
Glycol Succinate ◽  
Release Mechanism ◽  
Optimum Formula

Anastrozole (ANZ) is considered constitute of the fourth –generation of Non–steroidal aromatase blockage, ANZ has use for hormone receptor positive breast cancer in postmenopausal women. The serious side effects of ANZ including, vaginal dryness, hot flashes, irritability, breast tenderness and un–stability in circulation. Nanostructured lipid carriers (NLCs) have recently emerged as a multifunctional platform for drug delivery in cancer therapy. Five formula were composed of (200 mg of glyceryl monostearate, 40 mg of oleic acid , 1% (w/w) Tween 80, 1% (w/w) Poloxamer 407, 1% (w/w) soy lecithin and Vitamin E Polyethylene Glycol Succinate. The mean particle size, polydispersity index, zeta potential, entrapment efficiency, loading capacity range of optimum formula F05 (166±3.86 nm), (0.271±0.04), (–23.7±2.65 mV), (42.43±3.90%) and (1.23±0.35%) respectively that prepared by same above composition but higher amplitude value (70%). The in–vitro drug leakage study demonstrated intact formula through 5 hours, with an approximately 78.37% of the drug was encapsulated, that exhibit an anomalous release mechanism.

scholarly journals Discovery of Orexant and Anorexant Agents with Indazole Scaffold Endowed with Peripheral Antiedema Activity

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 492 ◽  
Author(s):  
Dimmito ◽  
Stefanucci ◽  
Pieretti ◽  
Minosi ◽  
Dvorácskó ◽  
...  
Keyword(s):  
Feeding Behavior ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Methyl Esters ◽  
Endocannabinoid System ◽  
Tail Flick ◽  
Binding Assays ◽  
Tail Flick Test

The endocannabinoid system represents an integrated neuronal network involved in the control of several organisms’ functions, such as feeding behavior. A series of hybrids of 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (mimonabant), a well-known inverse agonist of the type-1 cannabinoid receptor (CB1), once used as an antiobesity drug, and the N-(2S)-substitutes of 1-[(4-fluorophenyl)methyl]indazole-3-carboxamide with 1-amino-3-methyl-1-oxobutane (AB-Fubinaca), 1-amino-3,3-dimethyl-1-oxobutane (ADB-Fubinaca), and 3-methylbutanoate (AMB-Fubinaca), endowed with potent agonistic activity towards cannabinoid receptors CB1 and CB2 were in solution as C-terminal amides, acids, methyl esters and N-methyl amides. These compounds have been studied by binding assays to cannabinoid receptors and by functional receptor assays, using rat brain membranes in vitro. The most active among them as an agonist, (S)-1-(2,4-dichlorobenzyl)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-1H-indazole-3-carboxamide (LONI11), and an antagonist, (S)-2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoic acid (LONI4), were tested in vivo in mic, to evaluate their ability to stimulate or suppress feeding behavior after intraperitoneal (i.p.) administration. For a LONI11 formalin test and a tail flick test after an administration by the subcutaneous (s.c.) and intracerebroventricular (i.c.v.) routes, respectively, were also carried out in vivo in mice to investigate the antinociceptive property at the central and peripheral levesl. We observed a significant orexant effect for LONI11 and an intense anorexant effect for (S)-methyl 2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (LONI2) and LONI4. In zymosan-induced edema and hyperalgesia, LONI11 reduced the percent of paw volume increase and paw latency after s.c. administration, also suggesting a possible peripheral anti-inflammatory activity.

scholarly journals Bioavailability and Antidiabetic Activity of Gliclazide-Loaded Cubosomal Nanoparticles

2021 ◽  
Vol 14 (8) ◽  
pp. 786
Author(s):  
Mohamed Nasr ◽  
Saud Almawash ◽  
Ahmed Al Saqr ◽  
Alaa Y. Bazeed ◽  
Sameh Saber ◽  
...  
Keyword(s):  
Drug Release ◽  
Oral Absorption ◽  
Fold Increase ◽  
Poloxamer 407 ◽  
Antidiabetic Activity ◽  
Glyceryl Monooleate ◽  
In Vivo Absorption ◽  
Nanoparticles Dispersions

In this study, gliclazide-loaded cubosomal particles were prepared for improving the oral bioavailability and antidiabetic activity of gliclazide. Four formulations of gliclazide-loaded cubosomal nanoparticles dispersions were prepared by the emulsification method using four different concentrations of glyceryl monooleate (GMO) and poloxamer 407 (P407) as the stabilizer. The prepared formulations were in vitro and in vivo evaluated. In vitro, the prepared gliclazide-loaded cubosomal dispersions exhibited disaggregated regular poly-angular particles with a nanometer-sized particle range from 220.60 ± 1.39 to 234.00 ± 2.90 nm and entrapped 73.84 ± 3.03 to 88.81 ± 0.94 of gliclazide. In vitro gliclazide release from cubosomal nanoparticles revealed an initially higher drug release during the first 2 h in acidic pH medium; subsequently, a comparatively higher drug release in alkaline medium relative to gliclazide suspension was observed. An in vivo absorption study in rats revealed a two-fold increase in the bioavailability of gliclazide cubosomal formulation relative to plain gliclazide suspension. Moreover, the study of in vivo hypoglycemic activity indicated that a higher percentage reduction in glucose level was observed after the administration of gliclazide cubosomal nanoparticles to rats. In conclusion, gliclazide-loaded cubosomal nanoparticles could be a promising delivery system for improving the oral absorption and antidiabetic activity of gliclazide.

scholarly journals INCREASED RATE OF ACETYLCHOLINESTERASE SYNTHESIS IN DIFFERENTIATING NEUROBLASTOMA CELLS

1974 ◽  
Vol 63 (3) ◽  
pp. 824-830 ◽  
Author(s):  
Karl W. Lanks ◽  
Jan M. Dorwin ◽  
Bruno Papirmeister
Keyword(s):  
Specific Activity ◽  
Neuroblastoma Cells ◽  
Maximum Level ◽  
Fold Increase ◽  
Metabolic Inhibitors ◽  
Mrna Synthesis ◽  
Differentiated Cells ◽  
Induction Process ◽  
Lag Period

When neuroblastoma cells (N18) in vitro are maintained in the absence of serum, the specific activity of AChE begins to rise rapidly after an initial lag period of about 2–3 days, reaching a maximum level (10–20-fold increase) by 7 days after induction. In order to clarify the mechanism of induction, it was necessary to measure the rate of AChE synthesis and its sensitivity to metabolic inhibitors. Return of enzymatic activity after irreversible inhibition of AChE in "differentiated" cells was blocked by cycloheximide, but not by cordycepin or actinomycin D, suggesting that protein but not mRNA synthesis was required for replacement. By using the initial rate of this replacement as a measure of the rate of synthesis of the enzyme, it was shown that cells which had differentiated in the absence of serum synthesized AChE 50-fold faster on a specific activity basis than their undifferentiated counterparts. In contrast, cordycepin effectively blocked the increase in the rate of AChE synthesis that occurs as a result of serum deprivation, indicating that the induction process itself requires the synthesis of new mRNA. Axonation, another index of differentiation, was not completely blocked by inhibition of RNA or protein synthesis and presumably utilizes only pools of pre-existing structural proteins.

Ketamine Attenuates and Reverses Morphine Tolerance in Rodents

1996 ◽  
Vol 85 (6) ◽  
pp. 1357-1366. ◽  
Author(s):  
Naohito Shimoyama ◽  
Megumi Shimoyama ◽  
Charles E. Inturrisi ◽  
Kathryn J. Elliott
Keyword(s):  
Morphine Tolerance ◽  
Fold Increase ◽  
Response Analysis ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Aspartate Receptor ◽  
Tenfold Increase ◽  
Reverse Tolerance ◽  
Before And After ◽  
Development Of Tolerance

Background The development of tolerance complicates the use of morphine to manage persistent pain. N-methyl-D-aspartate receptor antagonists can attenuate or reverse morphine tolerance. The authors studied ketamine's ability to modulate morphine tolerance. Method Tolerance was produced in mice given morphine subcutaneously and was assessed by a cumulative dose-response analysis using the tail-flick test. The ability of ketamine at 0.3, 3, or 10 mg/kg given subcutaneously before and after morphine to attenuate the development of tolerance was assessed. The ability of 10 mg/kg ketamine to reverse tolerance produced by the subcutaneous implantation of morphine pellets to mice was also assessed. Rats were made tolerant to intraspinal morphine and the effects of the coadministration of 12 micrograms intraspinal ketamine were assessed. Results Morphine given subcutaneously produced a fivefold increase in the median effective (ED50) dose of morphine, which was dose-dependently attenuated by subcutaneously administered ketamine. A tenfold increase in the morphine ED50 produced by morphine pellets was completely reversed by ketamine given subcutaneously. Intraspinal morphine produced a 46-fold increase in its ED50, which was almost completely attenuated by the coadministration of intraspinal ketamine. Conclusions Systemically administered ketamine attenuates and reverses systemically induced morphine tolerance in mice, and intraspinal ketamine attenuates tolerance produced by intraspinal morphine in rats.

scholarly journals Preparation and In Vivo Evaluation of a Lidocaine Self-Nanoemulsifying Ointment with Glycerol Monostearate for Local Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1468
Author(s):  
Ji-Hyun Kang ◽  
Kwang-Hwi Yoo ◽  
Hyo-Young Park ◽  
Seung-Min Hyun ◽  
Sang-Duk Han ◽  
...  
Keyword(s):  
Local Anesthetic ◽  
The Self ◽  
In Vitro Dissolution ◽  
Tail Flick ◽  
Glycerol Monostearate ◽  
Depth Of Penetration ◽  
Tail Flick Test ◽  
Anesthetic Effect

Lidocaine, a commonly used local anesthetic, has recently been developed into a number of ointment products to treat hemorrhoids. This study examined its efficient delivery to the dermis through the pharmaceutical improvement of hemorrhoid treatment ointments. We attempted to increase the amount of skin deposition of lidocaine by forming a nanoemulsion through the self-nanoemulsifying effect that occurs when glycerol monostearate (GMS) is saturated with water. Using Raman mapping, the depth of penetration of lidocaine was visualized and confirmed, and the local anesthetic effect was evaluated via an in vivo tail-flick test. Evaluation of the physicochemical properties confirmed that lidocaine was amorphous and evenly dispersed in the ointment. The in vitro dissolution test confirmed that the nanoemulsifying effect of GMS accelerated the release of the drug from the ointment. At a specific concentration of GMS, lidocaine penetrated deeper into the dermis; the in vitro permeation test showed similar results. When compared with reference product A in the tail-flick test, the L5 and L6 compounds containing GMS had a significantly higher anesthetic effect. Altogether, the self-nanoemulsifying effect of GMS accelerated the release of lidocaine from the ointment. The compound with 5% GMS, the lowest concentration that saturated the dermis, was deemed most appropriate.

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