Antifungal Activity of Piperine-based Nanoemulsion Against Candida spp. via In Vitro Broth Microdilution Assay.

Candidemia leaves a trail of approximately 750,000 cases yearly, with a morbidity rate of up to 30%. While Candida albicans still ranks as the most predominantly isolated Candida species, C. glabrata comes in second, with a death rate of 40-50%. Although infections by Candida spp are commonly treated with azoles, the side effects and rise in resistance against it has significantly limited its clinical usage. The current study aims to address the insolubility of piperine and provide an alternative treatment to Candida infection by formulating a stable piperine-loaded O/W nanoemulsion, comprised of Cremophor RH40, Transcutol HP and Capryol 90 as surfactant, co-surfactant, and oil, respectively. Characterization with zetasizer showed the droplet size, polydispersity (PDI) and zetapotential value of the nanoemulsion to be 24.37 nm, 0.453 and -21.10 mV, respectively, with no observable physical changes such as phase separation from thermostability tests. FTIR peaks confirms presence of piperine within the nanoemulsion and TEM imaging visualized the droplet shape and further confirms the droplet size range of 20-24 nm. The MIC90 value of the piperine-loaded nanoemulsion determined with in vitro broth microdilution assay was approximately 20-50% lower than that of the pure piperine in DMSO, at a range of 0.8-2.0 mg/mL across all Candida spp. tested. Overall, the study showed that piperine can be formulated into a stable nanoemulsion, which significantly enhances its antifungal activity compared to piperine in DMSO.

Bioactive Hydrogel Formulation Based on Ferulic Acid-Grafted Nano-Chitosan and Bacterial Nanocellulose Enriched with Selenium Nanoparticles from Kombucha Fermentation.

Selenium nanoparticles (SeNPs) have specific properties that result from their biosynthesis particularities. Chitosan can prevent pathogenic biofilm development. A wide palette of bacterial nanocellulose (BNC) biological and physical-chemical properties are known. The aim of this study was to develop a hydrogel formulation (SeBNCSFa) based on ferulic acid-grafted chitosan and bacterial nanocellulose (BNC) enriched with SeNPs from Kombucha fermentation (SeNPsK), which could be used as an adjuvant for oral implant integration and other applications. The grafted chitosan and SeBNCSFa were characterized by biochemical and physical-chemical methods. The cell viability and proliferation of HGF-1 gingival fibroblasts were investigated, as well as their in vitro antioxidant activity. The inflammatory response was determined by enzyme-linked immunosorbent assay (ELISA) of the proinflammatory mediators (IL-6, TNF-α, and IL-1ß) in cell culture medium. Likewise, the amount of nitric oxide released was measured by the Griess reaction. The antimicrobial activity was also investigated. The grafting degree with ferulic acid was approximately 1.780 ± 0.07% of the total chitosan monomeric units, assuming single-site grafting per monomer. Fourier-transform infrared spectroscopy evidenced a convolution of BNC and grafted chitosan spectra, and X-ray diffraction analysis highlighted an amorphous rearrangement of the diffraction patterns, suggesting multiple interactions. The hydrogel showed a high degree of cytocompatibility, and enhanced antioxidant, anti-inflammatory, and antimicrobial potentials.

Pharmacokinetics and Histotoxic Profile of a Novel Azithromycin-Loaded Lipid-Based Nanoformulation.

Azithromycin traditional formulations possesses poor oral bioavailability which necessitates development of new formulation with enhanced bioavailability of the drug. The objective of current research was to explore the kinetics and safety profile of the newly developed azithromycin lipid-based nanoformulation (AZM-NF). In the in-vitro study of kinetics profiling, azithromycin (AZM) release was assessed using dialysis membrane enclosing equal quantity of either AZM-NF, oral suspension of azithromycin commercial product (AZM-CP), or azithromycin pure drug (AZM-PD) in simulated intestinal fluid. The ex-vivo study was performed using rabbit intestinal segments in physiological salts solution in a tissue bath. The in-vivo study was investigated by oral administration of AZM to rabbits while taking blood samples at predetermined time-intervals, followed by HPLC analysis. The toxicity study was conducted in rats to observe histopathological changes in rat's internal organs. In the in-vitro study, maximum release was 95.38 ± 4.58% for AZM-NF, 72.79 ± 8.85% for AZM-CP, and 46.13 ± 8.19% for AZM-PD (p < 0.0001). The ex-vivo investigation revealed maximum permeation of 85.68 ± 5.87 for AZM-NF and 64.88 ± 5.87% for AZM-CP (p < 0.001). The in-vivo kinetics showed Cmax 0.738 ± 0.038, and 0.599 ± 0.082 µg/ml with Tmax of 4 and 2 h for AZM-NF and AZM-CP respectively (p < 0.01). Histopathological examination revealed compromised myocardial fibers integrity by AZM-CP only, liver and kidney showed mild aberrations by both formulations, with no remarkable changes in the rest of studied organs. The results showed that AZM-NF exhibited significantly enhanced bioavailability with comparative safer profile to AZM-CP investigated.

NO-cGMP-K+ Channels Pathways Participate in the Antihypertensive Effects of Attalea phalerata Martius ex Spreng Oil-Loaded Nanocapsules.

Attalea phalerata Martius ex Spreng is a palm tree that is widely distributed in the Central-West region of Brazil. In this study, we investigated whether the oil-loaded nanocapsules of A. phalerata (APON) have acute and long-lasting antihypertensive effects in male spontaneously hypertensive rats (SHR), as well as explored the underlying molecular mechanisms. APON was prepared using the interfacial polymer deposition method. The particle size, polydispersity index, and zeta potential were investigated using dynamic and electrophoretic light scattering. The antihypertensive effects of APON (administered at doses of 1, 3, and 10 mg/kg) were evaluated after acute intraduodenal administration and after 7 days of oral treatment. To investigate the molecular pathways involved, we used pharmacological antagonists and inhibitors that target prostaglandin/cyclic adenosine monophosphate, nitric oxide/cyclic guanosine monophosphate, and potassium channels. Both acute and prolonged administration of APON (at doses of 3 and 10 mg/kg) resulted in a significant reduction in systolic, diastolic, and mean arterial pressure. Prior treatment with a non-selective nitric oxide synthase inhibitor (Nω-nitro-L-arginine methyl ester), guanylyl cyclase inhibitor (methylene blue), or non-selective calcium-sensitive K+ channel blocker (tetraethylammonium) abolished the antihypertensive effects of APON. Our study showed that A. phalerata oil-loaded nanocapsules have a significant antihypertensive effect in SHR after both short-term and long-term (7-day) use. This effect seems to rely on the vascular endothelium function and involves the NO-cGMP-K+ channel pathway. This research suggests a new direction for future studies to definitively prove the therapeutic benefits of APON in treating cardiovascular disease.

Nanoformulation-assisted microneedle transdermal drug delivery system: An innovative platform enhancing rheumatoid arthritis treatment.

A transdermal delivery system offers high bioavailability and favorable patient adherence, constituting an optimal approach for localized administration in rheumatoid arthritis (RA) treatment. However, the stratum corneum (SC) impedes the delivery efficiency of conventional transdermal drug delivery systems. Microneedles (MNs) can temporarily create micropores within the SC, enabling drug distribution via bypassing this barrier and enhancing transdermal delivery effectiveness. Notably, MNs provide a painless method of drug delivery through the skin and may directly modulate inflammation in immune cells by delivering drugs via the lymphatic system during transdermal administration. However, the MN delivery system is not suitable for drugs with low water solubility and stability. Additionally, major concerns exist regarding the safety of using MN delivery for highly cytotoxic drugs, given that it could result in high local drug concentration at the delivery site. While MNs exhibit some degree of targeted delivery to the immune and inflammatory environment, their targeting efficiency remains suboptimal. Nanoformulations have the potential to significantly address the limitations of MNs in RA treatment by improving drug targeting, solubility, stability, and biocompatibility. Therefore, this review provides a concise overview of the advantages, disadvantages, and mechanisms of different types of MNs for RA treatment. It specifically focuses on the application and advantages of combining nanoformulation with MNs for RA treatment and summarizes the current trends in the development of nanoformulations combined with MNs in the field of RA treatment, offering theoretical support for future advancements and clinical applications.

Tuning the photophysical properties of cyanine by barbiturate functionalization and nanoformulation for efficient optoacoustics- guided phototherapy.

Cyanine derivatives are organic dyes widely used for optical imaging. However, their potential in longitudinal optoacoustic imaging and photothermal therapy remains limited due to challenges such as poor chemical stability, poor photostability, and low photothermal conversion. In this study, we present a new structural modification for cyanine dyes by introducing a strongly electron-withdrawing group (barbiturate), resulting in a new series of barbiturate-cyanine dyes (BC810, BC885, and BC1010) with suppressed fluorescence and enhanced stability. Furthermore, the introduction of BC1010 into block copolymers (PEG114-b-PCL60) induces aggregation-caused quenching, further boosting the photothermal performance. The photophysical properties of nanoparticles (BC1010-NPs) include their remarkably broad absorption range from 900 to 1200 nm for optoacoustic imaging, allowing imaging applications in NIR-I and NIR-II windows. The combined effect of these strategies, including improved photostability, enhanced nonradiative relaxation, and aggregation-caused quenching, enables the detection of optoacoustic signals with high sensitivity and effective photothermal treatment of in vivo tumor models when BC1010-NPs are administered before irradiation with a 1064 nm laser. This research introduces a barbiturate-functionalized cyanine derivative with optimal properties for efficient optoacoustics-guided theranostic applications. This new compound holds significant potential for biomedical use, facilitating advancements in optoacoustic-guided diagnostic and therapeutic approaches.

Progress in Topical and Transdermal Drug Delivery Research-Focus on Nanoformulations.

Skin is the largest organ and a multifunctional interface between the body and its environment. It acts as a barrier against cold, heat, injuries, infections, chemicals, radiations or other exogeneous factors, and it is also known as the mirror of the soul. The skin is involved in body temperature regulation by the storage of fat and water. It is an interesting tissue in regard to the local and transdermal application of active ingredients for prevention or treatment of pathological conditions. Topical and transdermal delivery is an emerging route of drug and cosmetic administration. It is beneficial for avoiding side effects and rapid metabolism. Many pharmaceutical, technological and cosmetic innovations have been described and patented recently in the field. In this review, the main features of skin morphology and physiology are presented and are being followed by the description of classical and novel nanoparticulate dermal and transdermal drug formulations. The biophysical aspects of the penetration of drugs and cosmetics into or across the dermal barrier and their investigation in diffusion chambers, skin-on-a-chip devices, high-throughput measuring systems or with advanced analytical techniques are also shown. The current knowledge about mathematical modeling of skin penetration and the future perspectives are briefly discussed in the end, all also involving nanoparticulated systems.

"Click" amphotericin B in prodrug nanoformulations for enhanced systemic fungemia treatment.

Severe nephrotoxicity and infusion-related side effects pose significant obstacles to the clinical application of Amphotericin B (AmB) in life-threatening systemic fungal infections. In pursuit of a cost-effective and safe formulation, we have introduced multiple phenylboronic acid (PBA) moieties onto a linear dendritic telodendrimer (TD) scaffold, enabling effective AmB conjugation via boronate chemistry through a rapid, high yield, catalysis-free and dialysis-free "Click" drug loading process. Optimized AmB-TD prodrugs self-assemble into monodispersed micelles characterized by small particle sizes and neutral surface charges. AmB prodrugs sustain drug release in circulation, which is accelerated in response to the acidic pH and Reactive Oxygen Species (ROS) in the infection and inflammation. Prodrugs mitigate the AmB aggregation status, reduce cytotoxicity and hemolytic activity compared to Fungizone®, and demonstrate superior antifungal activity to AmBisome®. AmB-PEG5kBA4 has a comparable maximum tolerated dose (MTD) to AmBisome®, while over 20-fold increase than Fungizone®. A single dose of AmB-PEG5kBA4 demonstrates superior efficacy to Fungizone® and AmBisome® in treating systemic fungal infections in both immunocompetent and immunocompromised mice.

Testing of acute and sub-acute toxicity profile of novel naproxen sodium nanoformulation in male and female mice.

Nanodrugs offer promising alternatives to conventionally used over the counter drugs. Compared to its free form, therapeutic benefits, and gastric tissue safety of naproxen sodium nanoformulation (NpNF) were recently demonstrated. Essential regulatory safety data for this formulation are, however, not available. To address this, male and female BALB/c mice were subjected to acute and 14-day repeated-oral dose assessments. Our data indicate that NpNF was well tolerated up to 2000 mg/kg b.w. A 14-day subacute toxicity testing revealed that the oral administration of low dose (30 mg/kg) NpNF did not produce any adverse effects on blood profile and serum biochemical parameters. Levels of oxidative stress markers and antioxidant enzymes neared normal. Histology of selected tissues also showed no evidence of toxicity. In contrast, a ten-fold increase in NpNF dosage (300 mg/kg), demonstrated, irrespective of gender, mild to moderate toxicity (p < 0.05) in the brain, stomach, and heart tissues, while ROS, LPO, CAT, SOD, POD, and GSH levels remained unaffected in the liver, kidney, spleen, testis, and seminal vesicles. No effect on serum biochemical parameters, overall indicated a no-observed-adverse-effect level (NOAEL) is 300 mg/kg. Further increase in dosage (1000 mg/kg) significantly altered all parameters demonstrating that high dose is toxic.

New insights into the potential cardioprotective effects of telmisartan and nanoformulated extract of Spirulina platensis via regulation of oxidative stress, apoptosis, and autophagy in an experimental model.

Background: Cardiotoxicity is one of the limiting side effects of the commonly used anticancer agent cyclophosphamide (Cyclo). Materials and methods: The possible protective effects of telmisartan and nanoformulated Spirulina platensis (Sp) methanolic extract against Cyclo-induced cardiotoxicity were examined in this study. Experimental groups of rats were randomly divided into nine groups as control vehicle, control polymer, telmisartan (TEL, 10 mg/kg), free Sp extract (300 mg/kg), nano Sp extract (100 mg/kg), Cyclo (200 mg/kg), TEL + Cyclo, free Sp + Cyclo, and nano Sp + Cyclo. The groups with Cyclo combinations were treated in the same manner as their corresponding ones without Cyclo, with a single dose of Cyclo on day 18. Results: The results indicate that Cyclo causes significant cardiotoxicity, manifesting in the form of notable increases of 155.49%, 105.74%, 451.76%, and 826.07% in the serum levels of glutamic oxaloacetic transaminase (SGOT), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), and cardiac troponin I (cTnI) enzyme activities, respectively, as compared to the control. In addition, the cardiac glutathione (GSH) content and activity of glutathione peroxidase-1 (GPX-1) enzyme decreased by 65.94% and 73.85%, respectively. Treatment with nano Sp extract showed the most prominent restorations of the altered biochemical, histopathological, and immunohistochemical features as compared with those by TEL and free Sp; moreover, reductions of 30.64% and 43.02% in the p-AKT content as well as 60.43% and 75.30% of the endothelial nitric oxide synthase (eNOS) immunoreactivity were detected in the TEL and free Sp treatment groups, respectively. Interestingly, nano Sp boosted the autophagy signal via activation of beclin-1 (36.42% and 153.4%), activation of LC3II (69.13% and 195%), downregulation of p62 expressions (39.68% and 62.45%), and increased gene expressions of paraoxonase-1 (PON-1) (90.3% and 225.9%) compared to the TEL and free Sp treatment groups, respectively. Conclusion: The findings suggest the protective efficiency of telmisartan and nano Sp extract against cardiotoxicity via activations of the antioxidant, antiapoptotic, and autophagy signaling pathways.

Strategies to Improve the Transdermal Delivery of Poorly Water-Soluble Non-Steroidal Anti-Inflammatory Drugs.

The transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) has the potential to overcome some of the major disadvantages relating to oral NSAID usage, such as gastrointestinal adverse events and compliance. However, the poor solubility of many of the newer NSAIDs creates challenges in incorporating the drugs into formulations suitable for application to skin and may limit transdermal permeation, particularly if the goal is therapeutic systemic drug concentrations. This review is an overview of the various strategies used to increase the solubility of poorly soluble NSAIDs and enhance their permeation through skin, such as the modification of the vehicle, the modification of or bypassing the barrier function of the skin, and using advanced nano-sized formulations. Furthermore, the simple yet highly versatile microemulsion system has been found to be a cost-effective and highly successful technology to deliver poorly water-soluble NSAIDs.

Vaginal drug delivery system: A promising route of drug administration for local and systemic diseases.

Scientists around the globe have done cutting-edge research to facilitate the delivery of poorly absorbed drugs via various routes of administration and different delivery systems. The vaginal route of administration has emerged as a promising mode of drug delivery, attributed to its anatomy and physiology. Novel drug delivery systems overcome the demerits of conventional systems via nanobiotechnology. This review will focus on the disorders associated with women that are currently targeted by vaginal drug delivery systems. In addition, it will provide insights into innovations in drug formulations for the general benefit of women.

Phosphoenolpyruvate carboxykinase-1 targeted siRNA promotes wound healing in type 2 diabetic mice by restoring glucose homeostasis.

It is well-accepted that the liver plays a vital role in the metabolism of glucose and its homeostasis. Dysregulated hepatic glucose production and utilization, leads to type 2 diabetes (T2DM). In the current study, RNA sequencing and qRT-PCR analysis of nanoformulation-treated T2DM mice (TGthr group) revealed beneficial crosstalk of PCK-1 silencing with other pathways involved in T2DM. The comparison of precise genetic expression profiles of the different experimental groups showed significantly improved hepatic glucose, fatty acid metabolism and several other T2DM-associated crucial markers after the nanoformulation treatment. As a result of these improvements, we observed a significant acceleration in wound healing and improved insulin signaling in vascular endothelial cells in the TGthr group as compared to the T2DM group. Enhanced phosphorylation of PI3K/Akt pathway proteins in the TGthr group resulted in increased angiogenesis as observed by the increased expression of endothelial cell markers (CD31, CD34) thereby improving endothelial dysfunctions in the TGthr group. Additionally, therapeutic nanoformulation has been observed to improve the inflammatory cytokine profile in the TGthr group. Overall, our results demonstrated that the synthesized therapeutic nanoformulation referred to as GPR8:PCK-1siRNA holds the potential in ameliorating hyperglycemia-associated complications such as delayed wound healing in diabetes.

Customized Proteinaceous Nanoformulation for In Vivo Chemical Reprogramming.

Sweat gland (SwG) regeneration is crucial for the functional rehabilitation of burn patients. In vivo chemical reprogramming that harnessing the patient's own cells in damaged tissue is of substantial interest to regenerate organs endogenously by pharmacological manipulation, which could compensate for tissue loss in devastating diseases and injuries, for example, burns. However, achieving in vivo chemical reprogramming is challenging due to the low reprogramming efficiency and an unfavorable tissue environment. Herein, this work has developed a functionalized proteinaceous nanoformulation delivery system containing prefabricated epidermal growth factor structure for on-demand delivery of a cocktail of seven SwG reprogramming components to the dermal site. Such a chemical reprogramming system can efficiently induce the conversion of epidermal keratinocytes into SwG myoepithelial cells, resulting in successful in situ regeneration of functional SwGs. Notably, in vivo chemical reprogramming of SwGs is achieved for the first time with an impressive efficiency of 30.6%, surpassing previously reported efficiencies. Overall, this proteinaceous nanoformulation provides a platform for coordinating the target delivery of multiple pharmacological agents and facilitating in vivo SwG reprogramming by chemicals. This advancement greatly improves the clinical accessibility of in vivo reprogramming and offers a non-surgical, non-viral, and cell-free strategy for in situ SwG regeneration.

Unveiling the Role of Nano-Formulated Red Algae Extract in Cancer Management.

Cancer is one of the major causes of death, and its negative impact continues to rise globally. Chemotherapy, which is the most common therapy, has several limitations due to its tremendous side effects. Therefore, developing an alternate therapeutic agent with high biocompatibility is indeed needed. The anti-oxidative effects and bioactivities of several different crude extracts of marine algae have been evaluated both in vitro and in vivo. In the present study, we synthesized the aqueous extract (HA) from the marine algae Amphiroa anceps, and then, a liposome was formulated for that extract (NHA). The extracts were characterized using different photophysical tools like dynamic light scattering, UV-visible spectroscopy, FTIR, scanning electron microscopy, and GC-MS analysis. The SEM image revealed a size range of 112-185 nm for NHA and the GC-MS results showed the presence of octadecanoic acid and n-Hexadecanoic acid in the majority. The anticancer activity was studied using A549 cells, and the NHA inhibited the cancer cells dose-dependently, with the highest killing of 92% at 100 µg/mL. The in vivo studies in the zebrafish model showed that neither the HA nor NHA of Amphiroa anceps showed any teratogenic effect. The outcome of our study showed that NHA can be a potential drug candidate for inhibiting cancer with good biocompatibility up to a dose of 100 µg/mL.

An Indocyanine Green-Based Nanocluster for Imaging Orthodox Endometriosis Lesions with Negative Contrast.

Indocyanine green (ICG), as the sole near-infrared dye FDA-approved, is limited in biomedical applications because of its poor photostability, lack of targeting, and rapid removal in vivo. Herein, we presented a nanoformulation of poly-l-lysine-indocyanine green-hyaluronic acid (PIH) and demonstrated that it can image orthodox endometriosis (EM) lesions with a negative contrast. The PIH nanocluster, with an average diameter of approximately 200 nm, exhibited improved fluorescence photostability and antioxidant ability compared to free ICG. In the in vivo imaging, EM lesions were visualized, featuring apparent voids and clear boundaries. After colocalizing with the green fluorescent protein, we concluded that the contrast provided by PIH peaked at 4 h postinjection and was observable for at least 8 h. The negative contrast, clear boundaries, and enhanced observable time might be due to the low permeation of PIH to lesions and the enhanced retention on the surfaces of lesions. Thus, our findings suggest an ICG-based nanoprobe with the potential to diagnose abdominal diseases.

Self Emulsifying Delivery System of Cissus quadrangularis: Evidence of Enhanced Efficacy and Promising Pharmacokinetic Profile in the Management of Osteoporosis.

Treatment therapies used to manage osteoporosis are associated with severe side effects. So worldwide herbs are widely studied to develop alternative safe & effective treatments. Cissus quadrangularis (CQ) has a significant role in bone health and fracture healing. It is documented that its extracts increase osteoblastic differentiation & mineralization. Currently, Cissus quadrangularis is available in the form of tablets in the market for oral delivery. But these conventional forms are associated with poor bioavailability. There is a need for a novel drug delivery system with improving oral bioavailability. Therefore, a Cissus quadrangularis-loaded self-emulsifying drug delivery system (CQ-SEDDS) was developed which disperses rapidly in the gastrointestinal fluids, yielding nano-emulsions containing a solubilized drug. This solubilized form of the drug can be easily absorbed through lymphatic pathways and bypass the hepatic first-pass effect. The emulsification efficiency, zeta potential, globule size, in-vitro dissolution, ex-vivo, in-vivo and bone marker studies were performed to assess the absorption and permeation potential of CQ incorporated in SEDDS. CQ-SEDDS with excipients Tween 80, Cremophor RH40, Transcutol HP & α-Tocopherol acetate had shown about 76% enhancement in the bioavailability of active constituents of CQ. This study provided the pre-clinical data of CQ-SEDDS using osteoporotic rat model studies.

Protein coupled thionine acetate probed silica nanoparticles: An integrated laser-assisted therapeutic approach for treating cancer.

Herein, we report a multifaceted nanoformulation, developed by binding thionine acetate (TA) in silica matrix to form TA loaded silica nanoparticles (STA Nps), which were characterized using various physicochemical techniques. STA NPs were spherical shaped having size 40-50 nm and exhibited good heating efficiency, improved photostability and singlet oxygen production rate than TA alone. In PDT experiment, the rate of degradation for ABDMA was enhanced from 0.1367 min-1 for TA alone to 0.1774 min-1 for STA Nps, depicting an increase in the reactive oxygen species (ROS) generation ability of STA Nps. Further, the cytotoxicity of STA Nps was investigated by carrying out the biophysical studies with Calf thymus DNA (Ct-DNA) and Human Serum Albumin (HSA). The results indicated that the binding of STA Nps to Ct-DNA causes alterations in the double helix structure of DNA and as a result, STA Nps can impart chemotherapeutic effects via targeting DNA. STA Nps showed good binding affinity with HSA without compromising the structure of HSA, which is important for STA Nps sustainable biodistribution and pharmacokinetics. Based on this study, it is suggested that because of the synergistic effect of chemo and phototherapy, STA Nps can be extensively utilized as potential candidates for treating cancer.

Fisetin-loaded chitosan nanoparticles ameliorate pilocarpine-induced temporal lobe epilepsy and associated neurobehavioral alterations in mice: Role of ROS/TNF-α-NLRP3 inflammasomes pathway.

Fisetin has displayed potential as an anticonvulsant in preclinical studies yet lacks clinical validation. Challenges like low solubility and rapid metabolism may limit its efficacy. This study explores fisetin-loaded chitosan nanoparticles (NP) to address these issues. Using a murine model of pilocarpine-induced temporal lobe epilepsy, we evaluated the anticonvulsant and neuroprotective effects of fisetin NP. Pilocarpine-induced seizures and associated neurobehavioral deficits were assessed after administering subtherapeutic doses of free fisetin and fisetin NP. Changes in ROS, inflammatory cytokines, and NLRP3/IL-18 expression in different brain regions were estimated. The results demonstrate that the fisetin NP exerts protection against seizures and associated depression-like behavior and memory impairment. Furthermore, biochemical, and histological examinations supported behavioral findings suggesting attenuation of ROS/TNF-α-NLRP3 inflammasome pathway as a neuroprotective mechanism of fisetin NP. These findings highlight the improved pharmacodynamics of fisetin using fisetin NP against epilepsy, suggesting a promising therapeutic approach against epilepsy and associated behavioral deficits.

Cubosomal nanoformulation increase invitro dissolution and anticancer activity of Fisetin in A549 lung cancer cells.

Aim: To prepare fisetin (FIS) cubosomal nanoformulation to increase aqueous solubility and anticancer activity. Methods: Top-down method using glyceryl monooleate (GMO) and Pluronic F-127. Results: Optimized using 2% GMO and 1% Pluronic F-127, reported 93.07 nm particle size, 80.10% drug entrapment, and reports more than 50% enhanced in vitro drug release than native FIS. MTT assay reports IC50 Values of FIS 16.59 µg/ml and optimized cubosomal FIS nanoformulation (FISCUB) 12.18 µg/ml. The colony numbers observed in clonogenic assay for FISCUB were 8.33 ± 0.58 and FIS 11.67 ± 1.15. In flow cytometry study, apoptotic cells in FISCUB and FIS-treated A549 cells were found to be 33.4 and 6.83% respectively. Conclusion: A stable cubosomal nanoformulation of FIS showed enhanced aqueous solubility and anticancer activity.