Advanced multifunctional nano-lipid carrier loaded gel for targeted delivery of 5-flurouracil and cannabidiol against non-melanoma skin cancer.

Non-melanoma skin cancer is one of the most common malignancies reported around the globe. Current treatment therapies fail to meet the desired therapeutic efficacy due to high degree of drug resistance. Thus, there is prominent demand in advancing the current conventional therapy to achieve desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The current investigation has been designed to evaluate the safety and efficacy of developed 5-Flurouracil and cannabidiol loaded combinatorial lipid-based nanocarrier (FU-CBD NLCs) gel for the effective treatment of skin cancer. Initially, confocal microscopy study results showed excellent uptake and deposition at epidermal and the dermal layer. Irritation studies performed by IR camera and HET cam shows FU-CBD NLCs was much more tolerated and less irritant compared to conventional treatment. Furthermore, gamma scintigraphy evaluation shows the skin retention behavior of the formulation. Later, in-ovo tumor remission studies were performed, and it was found that prepared FU-CBD NLCs was able to reduce tumor volume significantly compared to conventional formulation. Thus, obtained results disclosed that permeation and disposition of 5-FU and CBD into different layers of the skin FU-CBD NLCs gel could be more potential carrier than conventional gel. Furthermore, prepared formulation showed greater tumor remission, better survival rate, reduction in tumor number, area, and volume with improved biochemical profile. Thus, prepared gel could serve as a promising formulation approach for the skin cancer treatment.

Precision medicine: Ray of hope in overcoming cancer multidrug resistance.

Multi-drug resistance (MDR) developed in response to chemotherapy is one of the prominent causes of therapeutic failure. The major underlying factors that contribute to such malignancies include tumor microenvironment, genetic alterations, changes at the cellular level and most of all the heterogeneity of tumors. Recent advances in the field of oncology have prompted a mechanistic understanding of the human genome which is responsible for such alterations, upon which the therapy would be designed. Such an approach that administers drugs by targeting the molecular changes is attributed to precision medicine. Precision medicine helps design therapy as per the requirement of patients based on the sharing of similar complex tumor environments. This revolutionized approach would help in early detection, better targeting, improved patient compliance and survival along with much reduced toxicity otherwise evidenced in conventional cancer therapy. This review discusses the cause of MDR, highlighting the role of precision medicine in overcoming such critical events. Major limitations and future prospects are also highlighted.

Intranasal inorganic cerium oxide nanoparticles ameliorate oxidative stress induced motor manifestations in haloperidol-induced parkinsonism.

Cerium oxide nanoparticles (CONPs), owing to their radical scavenging property, have recently emerged as a therapeutic candidate for oxidative stress-mediated neurological diseases. However, oral and intravenous administration of CONPs is limited due to their poor physicochemical characteristics, low bioavailability, rapid systemic clearance, poor blood-brain penetration and dose-dependent toxicity. To overcome these challenges, we developed intranasal CONPs and evaluated their potential in the experimental PD model. CONPs were prepared by homogenous precipitation using tween 80 as a stabilizer and methanol/water as solvent. The optimization was done using Central Composite Design (CCD). The CONPs synthesis was confirmed by UV and FTIR. The optimized CONPs were small-sized (105.1 ± 5.78 nm), spherical (TEM), uniform (PDI, 0.119 ± 0.006) and stable (ZP, -22.7 ± 1.02 mV). Energy-dispersive X-ray analysis showed characteristic signals of Ce in developed CONPs. The X-ray diffraction pattern described the cubic fluorite structure and nano-crystalline nature of CONPs. The CONP anti-oxidant activity was found to be 93.60 ± 0.32% at 25 µg/mL concentration. Finally, motor manifestation studies like the forced swim test, locomotor test, akinesia, catalepsy, and muscle coordination test were conducted to assess the motor dysfunctions and behavioral activity in all four animal groups. Results of the in vivo motor manifestation studies in the haloperidol-induced PD rat model showed that co-administration of intranasal CONPs along with a half dose of levodopa resulted in significant protection, and results were significantly different from the untreated group but not significantly different from the healthy group. In conclusion, intranasal CONPs can be useful in ameliorating oxidative stress through their antioxidant effect and could be prospective therapeutics for the treatment of motor manifestations in Parkinson's disease.

Comparison of Extrapyramidal Symptoms Among Outpatients With Schizophrenia on Long-Acting Injectable Antipsychotics.

BACKGROUND: Extrapyramidal symptoms (EPSs) are adverse effects of antipsychotics. Different risks of EPSs have been attributed to the 3 classes of antipsychotics. This study aimed to assess EPS in a clinical sample of schizophrenia patients who are on LAI and compare the severity of EPSs among the following 3 antipsychotic groups: (1) partial agonist, (2) second-generation antipsychotics, and (3) first-generation antipsychotics. METHODS: Ninety-two patients were recruited from the Schizophrenia Program Injection Clinic. Using the Extrapyramidal Symptom Rating Scale (ESRS), severity of EPS was assessed and information regarding factors associated with risk of EPS, including coprescriptions, comorbidities, and demographics, was obtained from medical charts. Group differences in ESRS scores and subscores were analyzed using 1-way analyses of variances. RESULTS: Among the 3 groups, there was no significant difference in total ESRS scores and subscores. Risperidone was associated with higher ESRS scores when compared with paliperidone, aripiprazole, and flupenthixol. Doses above maximum were commonly used in the paliperidone group, and there was no significant difference in total ESRS scores between the low, average, or above-maximum doses of paliperidone. CONCLUSIONS: Our results demonstrated a comparative risk of EPS across all 3 antipsychotic classes. Risperidone was associated with more EPS compared with other medications. A higher threshold for the "maximum dose" of paliperidone could be considered and higher doses used with the same cautions as low-average doses.

Epidemiology, virology and clinical aspects of hantavirus infections: an overview.

At the end of 2019 and 2020s, a wave of coronavirus disease 19 (COVID-19) epidemics worldwide has catalyzed a new era of 'communicable infectious diseases'. However, the world is not currently prepared to deal with the growing burden of COVID-19, with the unexpected arrival of Hantavirus infection heading to the next several healthcare emergencies in public. Hantavirus is a significant class of zoonotic pathogens of negative-sense single-stranded ribonucleic acid (RNA). Hemorrhagic renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) are the two major clinical manifestations. Till date, there is no effective treatments or vaccines available, public awareness and precautionary measures can help to reduce the spread of hantavirus disease. In this study, we outline the epidemiology, virology, clinical aspects, and existing HFRS and HCPS management approaches. This review will give an understanding of virus-host interactions and will help for the early preparation and effective handling of further outbreaks in an ever-changing environment.

Embelin ameliorates cognitive dysfunction and progression of kindling in pentylenetetrazol-induced kindling in mice by attenuating brain inflammation.

OBJECTIVE: This study was conducted to evaluate the effect of embelin (EMB) on various epileptic models and related brain inflammation. METHODS: Male Swiss albino mice were administered EMB (5, 10, and 20 mg/kg/p.o.) in acute and chronic study for 7 days and 35 days, respectively. Acute study included increasing current electroshock (ICES) and pentylenetetrazol (PTZ)-induced seizure test. Step-down latency (SDL) and forced swim test (FST) were performed to evaluate cognitive functions and depression-like behavior, respectively. Chronic study included PTZ-induced kindling. Levels of inflammatory biomarkers, namely interleukin-1 beta (IL-1ß), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were estimated in the hippocampus and cortex of the kindled brains by ELISA technique. Further, neurotransmitters (NTs), namely gamma aminobutyric acid (GABA), glutamate, and dopamine, were estimated by using validated liquid chromatography-mass spectrometry (LC-MS) method followed by ultra-high-performance liquid chromatography (UHPLC). RESULTS: Embelin (EMB) treatment increased the seizure threshold to hind limb extension (HLE) in the ICES test and decreased the seizure scores in the kindling experiment. Significantly low levels of IL-1ß, IL-1Ra, IL-6, and TNF-α were observed in the hippocampus of PTZ + EMB (10 and 20 mg/kg)-treated groups compared with PTZ+ vehicle-treated group. Significantly lower levels of IL-1Ra, IL-6, and TNF-α compared with PTZ+ vehicle-treated group were observed in the cortex of PTZ + EMB (10 and 20 mg/kg)-treated groups, while IL-1ß levels were found to be significantly lower only in the cortex of PTZ + EMB (20 mg/kg)-treated group. Increased levels of dopamine and GABA and decreased levels of glutamate in both hippocampus and cortex were observed in EMB + PTZ-treated groups compared with vehicle + PTZ-treated group. Latency of step down was found to be increased and immobility time in FST was decreased in EMB + PTZ groups compared with vehicle + PTZ group. CONCLUSION: Embelin suppressed epileptogenesis in the kindled mice via neurochemical modulation of neurotransmitters and inhibiting the inflammatory pathway. Further, EMB was also observed to be protecting the kindled animals from cognition and depression-like behavior.

Polyoliposomes: novel polyol-modified lipidic nanovesicles for dermal and transdermal delivery of drugs.

Various lipid nanovesicular systems have been developed with the aim to enhance the delivery of drugs via transdermal route. However, their clinical applications are often limited due to the barrier nature of skin and lack of flexibility. Herein, we have modified the conventional nanoliposomes (CLs) prepared by a thin-film hydration method by the addition of a polyol (glycerol) to form novel lipid nanovesicular structures termed 'POLYOLIPOSOMES' (PLs). They were further named as PL-B (before film formation) and PL-A (after film formation), depending on the stage of glycerol addition during production. Optimized CLs, PL-B and PL-A showed spherical nanovesicles and hydrodynamic diameter of 181.3 ± 4.11 nm, 114.2 ± 7.21 nm and 170.2 ± 6.51 nm, respectively. PLs showed significantly higher % entrapment efficiency and deformability index in comparison to CLs, indicating their higher flexibility. Furthermore, DSC and attenuated total relection (ATR)-Fourier transform infrared (FTIR) studies revealed the intercalation of glycerol into the lipid bilayer of PLs and interaction between nanovesicles and skin. Moreover, ex vivo and in vivo skin permeation studies confirmed the enhanced drug delivery of PLs via the transdermal route. Taken together, these results illustrate the potential of PLs as a novel lipid nanovesicular system for drug delivery via the transdermal route for both systematic (PL-B) as well as cutaneous diseases (PL-A).

Development and in vitro/in vivo evaluation of artemether and lumefantrine co-loaded nanoliposomes for parenteral delivery.

Combination therapy of artemether (ART) and lumefantrine (LUM) is well-established for the treatment of uncomplicated malaria worldwide. Nanoliposomes (NLs) encapsulating both drugs were prepared and freeze-dried. The lyophilized nanoliposomes exhibited high entrapment efficiency of artemether (66.18%), relatively low entrapment efficiency of lumefantrine (53.46%), low average size diameter (125.3 nm) and found to be stable at 4 °C for 60 days without significant change in mean particle diameter and drug entrapment efficiencies. In vitro drug release study has shown initial burst effect and then sustained release pattern over a time period of 30 h. In vivo toxicity study was examined by liver and kidney function test as well as histopathological examination. Nanoliposomes showed lower hemolytic potential (∼10%) compared to all the components when studied individually. There was no significant change (p > 0.05) in biochemical parametes between control and treated group of animals. Pharmacokinetic data of ART + LUM NLs showed higher the area under the plasma concentration-time curve (AUC) values and prolonged residence time of drug in the blood circulation compared with ART + LUM solution. The tissue distribution demonstrated high uptake of ART + LUM-NLs in RES organs particularly in liver and spleen. Biocompatibility was confirmed by hepato- and nephrotoxicity analysis showed no sign of fibrosis, fatty infiltration, centrilobular necrosis and lymphocyte infiltration confirmed the suitability of developed formulation for treatment of malaria.

A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives.

In the modern world, a number of therapeutic proteins such as vaccines, antigens, and hormones are being developed utilizing different sophisticated biotechnological techniques like recombinant DNA technology and protein purification. However, the major glitches in the optimal utilization of therapeutic proteins and peptides by the oral route are their extensive hepatic first-pass metabolism, degradation in the gastrointestinal tract (presence of enzymes and pH-dependent factors), large molecular size and poor permeation. These problems can be overcome by adopting techniques such as chemical transformation of protein structures, enzyme inhibitors, mucoadhesive polymers and permeation enhancers. Being invasive, parenteral route is inconvenient for the administration of protein and peptides, several research endeavors have been undertaken to formulate a better delivery system for proteins and peptides with major emphasis on non-invasive routes such as oral, transdermal, vaginal, rectal, pulmonary and intrauterine. This review article emphasizes on the recent advancements made in the delivery of protein and peptides by a non-invasive (peroral) route into the body.

In Vitro and In Vivo Scalp Retention and Penetration of 99mTc-Minoxidil Solution.

The present study assessed the effect of retention on ex vivo skin and in vivo scalp penetration of radiolabeled minoxidil formulations (5% w/v). Minoxidil was radiolabeled with technetium (99mTc) with an efficiency of 99.1% using 0.2% stannous chloride as reducing agent at pH 6 and incubation temperature of 40 °C. Three different 99mTc-minoxidil formulations were prepared using aqueous ethanolic solution as vehicle. Formulation A contains 99mTc-minoxidil dissolved in vehicle, formulation B contains 10% propylene glycol (PG) and formulation C contains 10% hydroxypropyl cellulose (HPC), in addition. Results showed that addition of HPC resulted in enhanced viscosity (400 mPa.s) and significantly higher ex vivo retention (p < 0.05) and permeation (0.75±0.12%, 8 h). PG does not improve the permeation and the results (0.44±0.05%, 8 h) were not significantly different from vehicle alone (0.40±0.05%, 8 h). The results of the in vivo human scalp studies corroborated with the ex vivo results and addition of hydroxypropyl cellulose (HPH) showed significantly higher (p < 0.05) scalp retention. Post 8 h application, scalp penetration in group treated with formulation C was nearly 2.8-fold and 2.2-fold higher than those treated with formulation A and B, respectively. Further, absence of minoxidil in systemic circulation during study duration indicates safety. In conclusion, our results showed that increasing contact time of minoxidil with scalp by modifying viscosity results in reduced frequency of application and improved efficacy.

Evaluation of three different 99mTc-based mock-venom agents for lymphoscintigraphy studies in preclinical models of peripheral snakebite envenomation.

Snakebite envenomation is one of the major public health concerns across many countries; with the WHO designating it as a 'priority neglected tropical disease' and stressing for a need to develop novel therapeutic strategies to reduce death and disability rate by end of 2030. Since a major component of venom; the high molecular weight (HMw) toxins enter the bloodstream through lymphatic system, research is focusing on modulating the lymphatic flow rate after topical application of suitable drug candidates. Present study compared the suitability of three radiopharmaceutical agents, namely 99mTc-Sulfur colloid (SC), 99mTc-Phytate (Phy) and 99mTc-Human serum albumin (HSA), to be used as mock-venom agent in studying modulation in lymphatic flow rate in preclinical models of peripheral snakebite envenomation using lymphoscintigraphy studies. The study was performed in 72 Sprague Dawley rats; divided into six groups of 12 rats each. Control groups were given intradermal injection (1.29-1.48 MBq in 100 µl normal saline) of either 99mTc-Phy/ 99mTc-SC/ 99mTc-HSA into the tail as 'mock-venom'. In respective test groups, commercially available topical formulation (Anobliss® Cream) containing Nifedipine (Nif; 0.3% w/w) and Lidocaine (Lid; 1.5% w/w) was applied topically over the animals' lower body (tail and hind limbs) immediately within 20s of administering intradermal injection of the radiopharmaceutical. Any modulation in lymph transit time from periphery to systemic circulation was assessed using lymphoscintigraphy by taking dynamic gamma-scintigraphy images of 60s each till 1 h post-injection of the test radiopharmaceuticals. Significant difference in movement of the three radiopharmaceuticals was noted in terms of their lymphatic movement. 99mTc-Phy did not show significant travel through the lymphatics and the liver was faintly visualized in control as well as test intervention groups. In case of 99mTc-SC, significant changes in movement of the radiotracer after topical application of Nif/Lid in the test intervention groups were clearly noted in comparison to control (P < 0.05). Multiple numbers of lymph nodes (LNs) could be clearly visualized in control (5 ± 1 LNs) and test intervention groups (3 ± 1 LNs). Liver uptake was more prominent in control animals and it reduced significantly in test intervention groups. On the other hand, 99mTc-HSA showed lesser number of lymph nodes and higher accumulation in liver as compared to 99mTc-SC, suggesting very fast movement of this radiopharmaceutical. Results indicates that 99mTc-SC could be used as a suitable agent to mimic lymphatic transit behavior of HMw toxin components of snake venom and could therefore be used as a model in studying the effect of any test pharmacological intervention in modulating lymphatic transit rate. Additional advantage could be a significant reduction in the need for sacrificing large number of animals, particularly during initial screening phase of drug development cycle.

Pharmacokinetic and clinical comparison of super-bioavailable itraconazole and conventional itraconazole at different dosing in dermatophytosis.

Background: Due to changing face of dermatophytosis in India, many dermatologists practice different dosing patterns of itraconazole (ITZ). Recently, a new form of ITZ, super-bioavailable ITZ (SBITZ), has been commercialized to overcome the pharmacokinetic challenges of conventional ITZ (CITZ). Serum and sebum concentration of ITZ plays an important role in the management of dermatophytosis. Hence, the current study compares the rate and extent of serum and sebum concentration of SBITZ and CITZ at different dosing to determine their efficacy and safety in patients with dermatophytosis. Methods: This was an open-label, randomized, four-arm study including 40 adult patients diagnosed with glabrous tinea who were randomized equally into four groups to receive either CITZ-100-BD or CITZ-200-OD (2×100 mg capsules) or SBITZ-130-OD or SBITZ-100-OD (2×SBITZ-50 mg capsules) for 4 weeks. Serum and sebum samples were analysed at different time intervals along with clinical efficacy and safety. Results: For serum concentration, on day 28, the arithmetic mean and standard deviation (SD) for CITZ-100-BD, CITZ-200-OD, SB-130-OD and SB100-OD were 1262±233.5 ng/mL, 1704±261.6 ng/mL, 1770±268.9 ng/mL and 1520±231.7 ng/mL, respectively, which was statistically significant for OD dosing of ITZ/SBITZ over CITZ-100-BD. Similarly, for sebum concentration, the arithmetic mean and SD for CITZ-100-BD, CITZ-200-OD, SB-130-OD and SB-100-OD were 1042±163.45 ng/mg, 1423±192.46 ng/mg, 1534±227.55 ng/mg and 1107±182.35 ng/mg, respectively, which was statistically significant for SB-130-OD and CITZ-200-OD over CITZ-100-BD and SBITZ-100-OD dosing. No significant difference was noted between SBITZ-130 and CITZ-200 (p=0.25). Only two patients achieved complete cure in the SBITZ-130 group, whereas no patients achieved the same in other groups (p=0.47). All the dosages were very well tolerated with only 12 adverse events reported by ten patients in all groups. Conclusion: All formulations achieved desired serum and sebum concentrations required for efficacy in dermatophytosis, but SB 130 mg OD and CITZ 200 mg OD were statistically significant than other ITZ doses in achieving sebum concentration. Additionally, SBITZ 130 mg OD was bioequivalent to CITZ 200 mg OD and achieved similar results to those of CITZ 200 mg OD but at 35% lower drug concentrations.

Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats.

Introduction: Cerium oxide nanoparticles (CONPs) have been investigated for their therapeutic potential in Parkinson's disease (PD) due to their potent and regenerative antioxidant activity. In the present study, CONPs were used to ameliorate the oxidative stress caused by free radicals in haloperidol-induced PD in rats following intranasal administration. Method: The antioxidant potential of the CONPs was evaluated in vitro using ferric reducing antioxidant power (FRAP) assay. The penetration and local toxicity of the CONPs was evaluated ex-vivo using goat nasal mucosa. The acute local toxicity of intranasal CONPs was also studied in rat. Gamma scintigraphy was used to assess the targeted brain delivery of CONPs. Acute toxicity studies were performed in rats to demonstrate safety of intranasal CONPs. Further, open field test, pole test, biochemical estimations and brain histopathology was performed to evaluate efficacy of intranasal CONPs in haloperidol-induced PD rat model. Results: The FRAP assay revealed highest antioxidant activity of prepared CONPs at a concentration of 25 µg/mL. Confocal microscopy showed deep and homogenous distribution of CONPs in the goat nasal mucus layers. No signs of irritation or injury were seen in goat nasal membrane when treated with optimized CONPs. Scintigraphy studies in rats showed targeted brain delivery of intranasal CONPs and acute toxicity study demonstrated safety. The results of open field and pole test showed highly significant (p < 0.001) improvement in locomotor activity of rats treated with intranasal CONPs compared to untreated rats. Further, brain histopathology of treatment group rats showed reduced neurodegeneration with presence of more live cells. The amount of thiobarbituric acid reactive substances (TBARS) was reduced significantly, whereas the levels of catalase (CAT), superoxide dismutase (SOD), and GSH were increased significantly, while amounts of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) showed significant reduction after intranasal administration of CONPs. Also, the intranasal CONPs, significantly high (p < 0.001) dopamine concentration (13.93 ± 0.85 ng/mg protein) as compared to haloperidol-induced control rats (5.76 ± 0.70 ng/mg protein). Conclusion: The overall results concluded that the intranasal CONPs could be safe and effective therapeutics for the management of PD.

Dasatinib: a potential tyrosine kinase inhibitor to fight against multiple cancer malignancies.

Dasatinib is the 2nd generation TKI (Tyrosine Kinase Inhibitor) having the potential to treat numerous forms of leukemic and cancer patients and it is 300 times more potent than imatinib. Cancer is the major cause of death globally and need to enumerate novel strategies to coping with it. Various novel therapeutics introduced into the market for ease in treating various forms of cancer. We reviewed and evaluated all the related aspects of dasatinib, which can enhance the knowledge about dasatinib therapeutics methodology, pharmacodynamic and pharmacokinetics, side effects, advantages, disadvantages, various kinds of interactions and its novel formulations as well.

Repurposing Drugs as Novel Triple-negative Breast Cancer Therapeutics.

BACKGROUND: Triple-Negative Breast Cancer (TNBC) is the most aggressive form of Breast Cancer (BC), with high rates of metastasis and recurrence and limited treatment options. Chemotherapy and radiotherapy, for example, have several harmful side effects, and no FDA-approved therapies are currently available. Repurposing old clinically approved drugs to target various TNBC targets is a novel method that has fewer side effects and leads to successful, low-cost drug development in a shorter amount of time. Medicinal plants containing various phytoconstituents (flavonoids, alkaloids, phenols, essential oils, tannins, glycosides, lactones) play a very crucial role in combating various types of diseases and are used in the drug development process because of having lesser side effects. OBJECTIVE: The present review summarizes various categories of repurposed drugs that target multiple targets of TNBC, as well as phytochemical categories that target TNBC singly or in combination with old synthetic drugs. METHODS: Literature information was collected from various databases such as Pubmed, Web of Science, Scopus, and Medline to understand and clarify the role and mechanism of repurposed synthetic drugs and phytoconstituents against TNBC by using keywords like "breast cancer", "repurposed drugs", "TNBC" and "phytoconstituents". RESULTS: Various repurposed drugs and phytochemicals that target different signaling pathways and exert their cytotoxic activities on TNBC cells ultimately lead to cell apoptosis, reducing the recurrence rate and stopping the metastasis process. CONCLUSION: Inhibitory effects can be seen at various levels, providing information and evidence to researchers in the drug development process. As a result, more research and investigations are needed to develop better therapeutic treatment options for TNBC.

Topical Tacrolimus Progylcosomes Nano-Vesicles As a Potential Therapy for Experimental Dry Eye Syndrome.

The present work aimed to evaluate the efficacy of topical tacrolimus (0.01%) loaded propylene glycol (PG) modified nano-vesicles (Proglycosomes Nano-vesicles, PNVs) for the treatment of experimental dry eye syndrome (DES) in rabbits. DES was induced by topical application of atropine (1.0%) and benzalkonium chloride (0.1%) aqueous solution. PNVs treatment (PNV group) was compared with tacrolimus solution 0.01% (TAC group) and untreated group and healthy group were used as controls. PNV treated animals showed improved clinical performance with marked increase in tear production and tear break-up time (TBUT). Further, PNVs also subside ocular inflammation as evident from absence of matrix metalloprotenaise-9 and normal ocular surface temperature (32.3 ± 0.34 °C). Additionally, PNVs have positive effect on ocular and epithelial damage observed through low ocular surface staining score and improved globlet cell density. The PNV treatment was found to more effectively compared to TAC solution and most of the parameters were close to those of healthy animals. In conclusion, tacrolimus PNV formulation (0.01%) could be a potential therapy for treatment of dry eye syndrome.

Cannabis as a potential compound against various malignancies, legal aspects, advancement by exploiting nanotechnology and clinical trials.

Various preclinical and clinical studies exhibited the potential of cannabis against various diseases, including cancer and related pain. Subsequently, many efforts have been made to establish and develop cannabis-related products and make them available as prescription products. Moreover, FDA has already approved some cannabis-related products, and more advancement in this aspect is still going on. However, the approved product of cannabis is in oral dosage form, which exerts various limitations to achieve maximum therapeutic effects. A considerable translation is on a hike to improve bioavailability, and ultimately, the therapeutic efficacy of cannabis by the employment of nanotechnology. Besides the well-known psychotropic effects of cannabis upon the use at high doses, literature has also shown the importance of cannabis and its constituents in minimising the lethality of cancer in the preclinical models. This review discusses the history of cannabis, its legal aspect, safety profile, the mechanism by which cannabis combats with cancer, and the advancement of clinical therapy by exploiting nanotechnology. A brief discussion related to the role of cannabinoid in various cancers has also been incorporated. Lastly, the information regarding completed and ongoing trials have also been elaborated.

Precision and Advanced Nano-Phytopharmaceuticals for Therapeutic Applications.

Phytopharmaceuticals have been widely used globally since ancient times and acknowledged by healthcare professionals and patients for their superior therapeutic value and fewer side-effects compared to modern medicines. However, phytopharmaceuticals need a scientific and methodical approach to deliver their components and thereby improve patient compliance and treatment adherence. Dose reduction, improved bioavailability, receptor selective binding, and targeted delivery of phytopharmaceuticals can be likely achieved by molding them into specific nano-formulations. In recent decades, nanotechnology-based phytopharmaceuticals have emerged as potential therapeutic candidates for the treatment of various communicable and non-communicable diseases. Nanotechnology combined with phytopharmaceuticals broadens the therapeutic perspective and overcomes problems associated with plant medicine. The current review highlights the therapeutic application of various nano-phytopharmaceuticals in neurological, cardiovascular, pulmonary, and gastro-intestinal disorders. We conclude that nano-phytopharmaceuticals emerge as promising therapeutics for many pathological conditions with good compliance and higher acceptance.

Intranasal Cerium Oxide Nanoparticles Ameliorate Cognitive Function in Rats with Alzheimer's via Anti-Oxidative Pathway.

Cerium oxide nanoparticles (CNPs), owing to their antioxidant property, have recently emerged as therapeutic candidate for Alzheimer's disease (AD). However, intravenous CNPs are limited due to their poor physicochemical properties, rapid blood clearance and poor blood-brain penetration. Thus, we developed intranasal CNPs and evaluated its potential in experimental AD. CNPs were synthesized using homogenous precipitation method and optimized through Box-Behnken Design. The formation of CNPs was confirmed by UV spectroscopy and FTIR. The optimized CNP were spherical, small (134.0 ± 3.35 nm), uniform (PDI, 0.158 ± 0.0019) and stable (ZP, -21.8 ± 4.94 mV). The presence of Ce in CNPs was confirmed by energy-dispersive X-ray analysis. Further, the X-ray diffraction spectra revealed that the CNPs were nano-crystalline. The DPPH assay showed that at concentration of 50 µg/mL, the percentage radical scavenging was 95.40 ± 0.006%. Results of the in vivo behavioral studies in the scopolamine-induced Alzheimer rat model showed that intranasal CNPs dose dependently reversed cognitive ability. At dose of 6 mg/kg the morris water maze results (escape latency, path length and dwell time) and passive avoidance results (retention latency) were significantly different from untreated group but not significantly different from positive control group (rivastigmine patch, 13.3 mg/24 h). Further, biochemical estimation showed that intranasal CNP upregulated the levels of SOD and GSH in brain. In conclusion, intranasal CNPs, through its antioxidant effect, could be a prospective therapeutics for the treatment of cognitive impairment in AD.

Application of Nutraceuticals in Managing Osteoarthritis and Osteoporosis.

BACKGROUND: Several health problems, especially musculoskeletal disorders, are caused by differences in work cultures and human lifestyles around the world. While the conventional approach to treating such conditions emphasizes a balanced work-life and daily exercise, nutraceuticals have proven to be successful. Nutraceuticals are dietary compounds that help sustain cartilage metabolism homeostasis, reducing articular pain. Dietary intake of a variety of nutraceuticals is thought to be essential for controlling and, more specifically, preventing osteoarthritis and osteoporosis. OBJECTIVE: The current article offers a succinct overview in which data was gathered and searched using specific key terms related to nutraceuticals, osteoarthritis, and osteoporosis that were available in public domains for analysis and evaluation. METHODS: The current write-up offers a concise summary of disease and its relevance as to how nutraceuticals are helpful, based on the defined findings and their interpretation. The present review also discusses the existing literature, patents, and current studies in the era of nutraceuticals for osteoarthritis and osteoporosis treatment, offering a rational basis for further investigation and research. RESULT: This article discusses a wide variety of nutraceuticals with possible uses for osteoarthritis and osteoporosis patients. An analysis revealed that nutraceuticals' efficacy has been established. However, further study and investigation are needed to determine their protection. CONCLUSION: As a result of this analysis, it was concluded that more innovation and technology transfer were required. It was also concluded that greater industry-academic collaboration was required to begin more effective research in the treatment of osteoarthritis and osteoporosis with nutraceuticals.