Crisaborole loaded nanoemulgel for the mitigation of atopic dermatitis in mice model.

OBJECTIVE: The present work aims to formulate nanoemulgel of crisaborole (CB) and evaluate its effectiveness against 2,4-Di-nitrochlorobenzene induced (DNCB) atopic dermatitis (AD) in mice. SIGNIFICANCE: AD is a chronic inflammation of the skin affecting the quality of life. CB is a topical PDE4 inhibitor marketed as a 2% ointment. It, however, possesses poor aqueous solubility. An o/w nanoemulsion shall exhibit an enhanced therapeutic effect owing to the increased solubility of CB and an augmented skin penetration. The addition of a gelling agent to form a nanoemulgel further provides ease of application to the patients. METHODS: Nanoemulsion was prepared by aqueous titration method using caproyl PGMC, cremophore EL and propylene glycol as the oil, surfactant, and cosurfactant respectively. The formulations were characterized by their size, zeta potential and polydispersity index (PDI). 1% Carbopol 934 was used as the gelling agent to formulate nanoemulgel comprising of optimized nanoemulsion (NE 9). Ex vivo skin permeation of the CB nanoemulgel was compared with the CB ointment. Its therapeutic effect was evaluated in Balb/c mice. RESULTS: NE 9 comprised of 7.49% oil, 37.45% Smix (1:3) and water 55.06%. Its particle size, PDI and zeta potential were 15.45 ± 5.265 nm, 0.098 and -17.9 ± 8.00 mV respectively. The nanoemulgel exhibited a 3-fold higher permeation flux as compared to the ointment. In vivo studies demonstrated that the nanoemulgel provided better therapeutic effect than the ointment. CONCLUSION: We can thereby conclude that nanoemulgel formulation can be a successful drug delivery strategy for enhancing the therapeutic effect of CB.

A Discursive Review of Recent Development and Patents on Glycerosomes.

BACKGROUND: To achieve a target-based drug delivery with minimal side effects, novel drug delivery systems are being continuously explored. Vesicular systems are one such system that can ameliorate the bioavailability of the encapsulated drug by delivering the drug at the targeted site and can minimize the side effect. OBJECTIVE: The objective of this patent review is to provide a vivid description of glycerosomes and their applications. Glycerosomes are sphere-shaped versatile vesicles consisting of one or more phospholipid bilayers similar to liposomes but contain a high concentration of glycerol, which modifies the liposome bilayer fluidity. Glycerosomes can encapsulate both hydrophobic and hydrophilic drugs, which makes them the promising vehicle in the field of drug delivery. CONCLUSION: Most of the glycerosome formulations prepared were targeted for topical delivery and in particular, a cutaneous route where they have shown promising results. These vesicles are biocompatible and due to the high glycerol concentration, they have improved spreadability and penetrability. It is therefore imperative to explore the other topical routes such as ocular, vaginal, nasal, and rectal for delivery of drugs.

Carbon nanomaterials for the detection of pesticide residues in food: A review.

In agricultural fields, pesticides are widely used, but their residual presence in the environment poses a threat to humans, animals, insects, and ecosystems. The overuse of pesticides for pest control, enhancement of crop yield, etc. leaves behind a significant residual amount in the environment. Various robust, reliable, and reusable methods using a wide class of composites have been developed for the monitoring and controlling of pesticides. Researchers have discovered that carbon nanomaterials have a wide range of characteristics such as high porosity, conductivity and easy electron transfer that can be successfully used to detect pesticide residues from food. This review emphasizes the role of carbon nanomaterials in the field of pesticide residue analysis in different food matrices. The carbon nanomaterials including carbon nanotubes, carbon dots, carbon nanofibers, graphene/graphene oxides, and activated carbon fibres are discussed in the review. In addition, the review examines future prospects in this research area to help improve detection techniques for pesticides analysis.

Phytochemical: a treatment option for heavy metal induced neurotoxicity.

Heavy metals are known to be carcinogenic, mutagenic, and teratogenic. Some heavy metals are necessary while present in the growing medium in moderate concentrations known to be essential heavy metals as they required for the body functioning as a nutrient. But there are some unwanted metals and are also toxic to the environment and create a harmful impact on the body, which termed to be non-essential heavy metals. Upon exposure, the heavy metals decrease the major antioxidants of cells and enzymes with the thiol group and affect cell division, proliferation, and apoptosis. It interacts with the DNA repair mechanism and initiates the production of reactive oxygen species (ROS). It subsequently binds to the mitochondria and may inhibit respiratory and oxidative phosphorylation in even low concentrations. This mechanism leads to damage antioxidant repair mechanism of neuronal cells and turns into neurotoxicity. Now, phytochemicals have led to good practices in the health system. Phytochemicals that are present in the fruits and herbs can preserve upon free radical damage. Thus, this review paper summarized various phytochemicals which can be utilized as a treatment option to reverse the effect of the toxicity caused by the ingestion of heavy metals in our body through various environmental or lifestyles ways.

Efficacy of Flavonoids in Combating Fluconazole Resistant Oral Candidiasis.

BACKGROUND: Candida is an opportunistic fungus often present in the oral mucosa. In the compromised immune system, it may become pathogenic and cause oral candidiasis. This infection is more common with Candida albicans; though, non-albicans Candida spp also have significant relevance. Current treatment guidelines include polyenes, azoles and echinocandins, where fluconazole is the primary therapeutic option. However, both inherited and acquired resistance to fluconazole is exhaustively reported. The development of resistance has resulted in the worsening of the original and re-emergence of new fungal diseases. Thus, the development of an anti-candidiasis therapy with a satisfactory outcome is the urgent need of the hour. OBJECTIVE: This review article aims to stimulate research in establishing the synergistic efficacy of various flavonoids with fluconazole to combat the resistance and develop an effective pharmacotherapy for the treatment of oral candidiasis. Further, in this article, we discuss in detail the mechanisms of action of fluconazole, along with the molecular basis of the development of resistance in Candida species. METHODS: PubMed and other databases were used for literature search. RESULTS: The designing of natural drugs from the plant-derived phytochemicals are the promising alternatives in modern medicine. The challenge today is the development of alternative anti-oral candidiasis drugs with increased efficacy, bioavailability and better outcome which can combat azole resistance. Identifying the flavonoids with potential antifungal action at low concentrations seems to meet the challenges. CONCLUSION: Phyto-active constituents, either alone or in combination with conventional antibiotics may be an effective approach to deal with global antimicrobial resistance. The efficacy of herbal therapy for decades suggests that bacteria, fungi, and viruses may have a reduced ability to adapt and resistance to these natural antimicrobial regimes.

Chronic inhibition of central Angiotensin-converting enzyme ameliorates colchicine-induced memory impairment in mice.

Preclinical and clinical studies indicated involvement of the central renin-angiotensin system (RAS) in memory functions. However, the role of central angiotensin-converting enzyme (ACE) in memory function is still unclear. The present study investigated the involvement of central ACE in colchicine-induced memory impairment in the context of cholinergic function and oxidative stress. Memory impairment was induced by intracerebral colchicine administration in mice. The ACE inhibitor, perindopril (0.05 and 0.1 mg/kg/day), was administered orally for 14 days. Memory function was evaluated by the Morris water maze (MWM) test from the 14(th) day on after colchicine injection. Donepezil was used as a standard. Parameters of oxidative stress and cholinergic function, ACE activity in serum and the brain were estimated after the completion of behavioral studies. Colchicine caused memory impairment as revealed by no significant change in latency to reach a hidden platform in the MWM test. Furthermore, there was a significant increase in MDA, ROS, and nitrite levels with a reduction in GSH level and acetylcholinesterase (AChE) activity in the brain of colchicine-treated mice. Colchicine significantly increased brain ACE activity without affecting serum ACE. Donepezil prevented colchicine-induced memory impairment in mice. The antidementic effect of perindopril may be attributed to reduced oxidative stress and improvement in cholinergic function. Moreover, the elevated brain ACE activity was also inhibited by perindopril. The study showed that central ACE plays an important role in colchicine-induced memory deficit, corroborating a number of studies that show that treatment with ACE inhibitors could be neuroprotective.

Protective effect of quercetin against intracerebral streptozotocin induced reduction in cerebral blood flow and impairment of memory in mice.

The aim of the present study is to investigate the effect of quercetin, a naturally occurring flavonoid, on cerebral blood flow (CBF), brain energy metabolism, memory impairment, oxidative stress and cholinergic dysfunction in brain following intracerebral (i.c.) streptozotocin (STZ) administration in mice. STZ (0.5mg/kg, i.c.) was administered twice at an interval of 48h. We found a significant reduction in CBF as measured by Laser Doppler Flowmetry (LDF). The brain energy metabolism was also altered as evidenced by significant reduction in brain ATP content. Daily treatment with quercetin (2.5, 5 and 10mg/kg, p.o.) starting from the first dose of STZ showed a dose-dependent restoration of CBF and ATP content. Further, quercetin prevented STZ induced memory impairment as assessed by Morris water maze and passive avoidance tests. Biochemical analysis revealed that STZ significantly increased malondialdehyde (MDA), nitrite and depleted glutathione (GSH) levels in the mice brain. Quercetin decreased oxidative and nitrosative stress as evidenced by a significant decrease in MDA, nitrite and increase in GSH levels. Quercetin also attenuated elevated acetylcholinesterase activity in the STZ-treated mice. Neither STZ (i.c.) nor quercetin showed any change in locomotor activity and blood glucose level. The present study demonstrates the beneficial effects of quercetin in improving CBF along with preventing memory impairment, oxidative stress, altered brain energy metabolism and cholinergic dysfunction caused by STZ in mice. Therefore, consumption of dietary stuff rich in quercetin should be encouraged to ward off dementia associated with vascular and neurodegenerative disorders.

Protective effect of curcumin against intracerebral streptozotocin induced impairment in memory and cerebral blood flow.

AIMS: The aim of the present study is to investigate the effect of curcumin on cerebral blood flow (CBF), memory impairment, oxidative stress and cholinergic dysfunction in intracerebral (IC) streptozotocin (STZ) induced memory impairment in mice. MAIN METHODS: Memory impairment was induced by STZ (0.5mg/kg, IC) administered twice with an interval of 48h in mice. Memory function was assessed by Morris water maze and passive avoidance test. CBF was measured by Laser Doppler Flowmetry (LDF). To study the preventive effect, curcumin (10, 20 and 50mg/kg, PO) was administered for 21days starting from the first dose of STZ. In another set of experiment, curcumin was administered for 7days from 19th day after confirming STZ induced dementia to observe its therapeutic effect. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain on day 21. KEY FINDINGS: The major finding of this study is that STZ (IC) caused a significant reduction in CBF along with memory impairment, cholinergic dysfunction and enhanced oxidative stress. Curcumin dose dependently improved CBF in STZ treated mice together with amelioration of memory impairment both in preventive and therapeutic manner. SIGNIFICANCE: The present study clearly demonstrates the beneficial effects of curcumin, the dietary staple of India, on CBF, memory and oxidative stress which can be exploited for dementia associated with age related vascular and neurodegenerative disorders.

Candesartan improves memory decline in mice: involvement of AT1 receptors in memory deficit induced by intracerebral streptozotocin.

The Renin-angiotensin system, besides blood pressure regulation, affects learning and memory as evidenced by improvement of cognition in hypertensive patients being treated with AT1 receptor blockers like candesartan. The present study examined the influence of candesartan on memory impairment induced by intracerebral streptozotocin (IC STZ 0.5 mg/kg) in mice. Candesartan (0.05 mg/kg and 0.1 mg/kg, i.p.) was given for 14 days following IC STZ administration. The dose of 0.1 mg/kg significantly improved latency period in passive avoidance test. Further, treatment with 0.1 mg/kg candesartan for 14 days significantly improved spatial memory in mice in water maze test also. In another group, after memory impairment in mice following IC STZ administration, memory improving effect of a 7 days treatment with 0.1 mg/kg candesartan lasted only for 3 subsequent days in water maze task. IC STZ increased oxidative stress but pretreatment with 0.1 mg/kg candesartan decreased oxidative stress as indicated by a decrease in MDA and increase in GSH. Further, candesartan decreased free radicals as evidenced by flow cytometry. IC STZ affected cholinergic system also by increasing acetylcholine esterase activity that was restored by pretreatment with 0.1 mg/kg candesartan. Locomotor activity and serum glucose level remained unaffected by candesartan treatment. These results suggest that AT1 receptors play a facilitatory role in STZ induced memory deficit and corroborate number of human studies that AT1 receptor blockers can be used therapeutically against cognitive decline in hypertensive patients.