Fabrication, Characterization and Biomedical Evaluation of a Statistically Optimized Gelatin Scaffold Enriched with Co-Drugs Loaded into Controlled-Release Silica Nanoparticles.

The current study focused on the fabrication of a well-designed, biocompatible, physically stable, non-irritating and highly porous gelatin scaffold loaded with controlled-release triamcinolone acetonide (TA) and econazole nitrate (EN) co-loaded into mesoporous silica nanoparticles (EN-TA-loaded MSNs) to provide a better long-lasting antifungal therapeutic effect with minimal unfavorable effects. Optimization of the MSNs-loaded scaffold was performed using central composite rotatable design (CCRD), where the effect of gelatin concentration (X1), plasticizer (X2) and freezing time (X3) on the entrapment of EN (Y1) and TA (Y2) and on the release of EN (Y3) and TA (Y4) from the scaffold were studied. The significant compatibility of all formulation ingredients with both drugs was established from XRD, DSC and FT-IR spectra analyses while SEM and zeta studies represented a very precise unvarying distribution of the loaded MSNs in the porous structure of the scaffold. The stability of the optimized scaffold was confirmed from zeta potential analysis (-16.20 mV), and it exhibited higher entrapment efficiency (94%) and the slower (34%) release of both drugs. During in vitro and in vivo antifungal studies against Candida albicans, the MSNs-loaded scaffold was comparatively superior in the eradication of fungal infections as a greater zone of inhibition was observed for the optimized scaffold (16.91 mm) as compared to the pure drugs suspension (14.10 mm). Similarly, the MSNs-loaded scaffold showed a decreased cytotoxicity because the cell survival rate in the scaffold presence was 89% while the cell survival rate was 85% in the case of the pure drugs, and the MSNs-loaded scaffold did not indicate any grade of erythema on the skin in comparison to the pure medicinal agents. Conclusively, the scaffold-loaded nanoparticles containing the combined therapy appear to possess a strong prospective for enhancing patients' adherence and therapy tolerance by yielding improved synergistic antifungal efficacy at a low dose with abridged toxicity and augmented wound-healing impact.

ß-hydroxybutyric acid attenuates oxidative stress and improves markers of mitochondrial function in the HT-22 hippocampal cell line.

Ketone bodies have been the topic of research for their possible therapeutic neurotropic effects in various neurological diseases such as Parkinson's disease, dementia, and seizures. However, continuing research on ketone bodies as a prophylactic agent for decreasing the risk for various neurodegenerative diseases is currently required. In this paper, hippocampal HT-22 cells were treated with ß-hydroxybutyric acid at different doses to elucidate the neurotropic effects. In addition, markers of oxidative stress, mitochondrial function, and apoptosis were investigated. As a result, the ketone body (ß-hydroxybutyric acid) showed a significant increase in hippocampal neuronal viability at a moderate dose. Results show that ß-hydroxybutyric acid exhibited antioxidant effect by decreasing prooxidant oxidative stress markers such as reactive oxygen species, nitrite content, and increasing glutathione content leading to decreased lipid peroxidation. Results show that ß-hydroxybutyric acid improved mitochondrial functions by increasing Complex-I and Complex-IV activities and showing that ß-hydroxybutyric acid significantly reduces caspase-1 and caspase-3 activities. Finally, using computational pharmacokinetics and molecular modeling software, we validated the pharmacokinetic effects and pharmacodynamic (N-Methyl-D-aspartic acid and acetylcholinesterase) interactions of ß-hydroxybutyric acid. The computational studies demonstrate that ß-hydroxybutyric acid can interact with N-Methyl-D-aspartic acid receptor and cholinesterase enzyme (the prime pharmacodynamic targets for cognitive impairment) and further validates its oral absorption, distribution into the central nervous system. Therefore, this work highlights the neuroprotective potential of ketone bodies in cognitive-related neurodegenerative diseases.

Predictable hematological markers associated with cognitive decline in valid rodent models of cognitive impairment.

Endogenous (hyperglycemia) and exogenous (therapeutic, prophylactic, street drugs) factors can considerably contribute to cognitive impairment (CI). Currently, there are few invasive and/or noninvasive markers that correlate with CI and those that do exist require expensive or invasive techniques to predict and accurately measure the cognitive decline. Therefore, we sought to determine hematological markers as predictors of CI in two different chemically induced valid rodent models of CI (streptozotocin induced hyperglycemic model and chemotherapy [doxorubicin/cyclophosphamide] treated rodent model). Hematological markers were analyzed in the above rodent models of CI CI and compared to their respective control groups. There was a significant increase in creatinine kinase, lactate dehydrogenase and aspartate aminotransferase (AST) in the chemotherapy group. Blood urea nitrogen (BUN), alkaline phosphatase (ALP), bilirubin, creatinine and glucose levels were significantly increased in the streptozotocin group. Interestingly, triglycerides were significantly elevated in both the streptozotocin and chemotherapy groups. Previous studies with human subjects have shown a potential link between the increase in triglyceride levels and CI. Likewise, our data indicate a notable correlation with an increase in triglycerides to cognitive impairment in the rodent models. This suggests elevated levels of triglycerides could prove to be a potential noninvasive hematological marker for the increased risk of CI. Further studies are warranted to determine the causal relationship between elevated triglyceride levels and CI.

PPAR-δ Activation Ameliorates Diabetes-Induced Cognitive Dysfunction by Modulating Integrin-linked Kinase and AMPA Receptor Function.

An estimated 9% of the American population experiences type II diabetes mellitus (T2DM) due to diet or genetic predisposition. Recent reports indicate that patients with T2DM are at increased risk for cognitive dysfunctions, as observed in conditions like Alzheimer's disease (AD). In addition, AD is the leading cause of dementia, highlighting the urgency of developing novel therapeutic targets for T2DM-induced cognitive deficits. The peroxisome proliferator activated receptor-δ (PPAR-δ) is highly expressed in the brain and has been shown to play an important role in spatial memory and hippocampal neurogenesis. However, the effect of PPAR-δ agonists on T2DM-induced cognitive impairment has not been explored. In this study, the effects of GW0742 (a selective PPAR-δ agonist) on hippocampal synaptic transmission, plasticity, and spatial memory were investigated in the db/db mouse model of T2DM. Oral administration of GW0742 for 2 weeks significantly improved hippocampal long-term potentiation. In addition, GW0742 effectively prevented deficits in hippocampal dependent spatial memory in db/db mice. PPAR-δ-mediated improvements in synaptic plasticity and behavior were accompanied by a significant recovery in hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated synaptic transmission. Our findings suggest that activation of PPAR-δ might ameliorate T2DM-induced impairments in hippocampal synaptic plasticity and memory.

Doxorubicin-induced neurotoxicity is associated with acute alterations in synaptic plasticity, apoptosis, and lipid peroxidation.

Cognitive deficits are commonly reported by patients following treatment with chemotherapeutic agents. Anthracycline-containing chemotherapy regimens are associated with cognitive impairment and reductions in neuronal connectivity in cancer survivors, and doxorubicin (Dox) is a commonly used anthracycline. Although it has been reported that Dox distribution to the central nervous system (CNS) is limited, considerable Dox concentrations are observed in the brain with co-administration of certain medications. Additionally, pro-inflammatory cytokines, which are overproduced in cancer or in response to chemotherapy, can reduce the integrity of the blood-brain barrier (BBB). Therefore, the aim of this study was to evaluate the acute neurotoxic effects of Dox on hippocampal neurons. In this study, we utilized a hippocampal cell line (H19-7/IGF-IR) along with rodent hippocampal slices to evaluate the acute neurotoxic effects of Dox. Hippocampal slices were used to measure long-term potentiation (LTP), and expression of proteins was determined by immunoblotting. Cellular assays for mitochondrial complex activity and lipid peroxidation were also utilized. We observed reduction in LTP in hippocampal slices with Dox. In addition, lipid peroxidation was increased as measured by thiobarbituric acid reactive substances content indicating oxidative stress. Caspase-3 expression was increased indicating an increased propensity for cell death. Finally, the phosphorylation of signaling molecules which modulate LTP including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and Akt were increased. This data indicates that acute Dox exposure dose-dependently impairs synaptic processes associated with hippocampal neurotransmission, induces apoptosis, and increases lipid peroxidation leading to neurotoxicity.

Comparing the dopaminergic neurotoxic effects of benzylpiperazine and benzoylpiperazine.

Benzylpiperazine has been designated as Schedule I substance under the Controlled Substances Act by Drug Enforcement Administration. Benzylpiperazine is a piperazine derivative, elevates both dopamine and serotonin extracellular levels producing stimulatory and hallucinogenic effects, respectively, similar to methylenedioxymethamphetamine (MDMA). However, the comparative neurotoxic effects of Piperazine derivatives (benzylpiperazine and benzoylpiperazine) have not been elucidated. Here, piperazine derivatives (benzylpiperazine and benzoylpiperazine) were synthesized in our lab and the mechanisms of cellular-based neurotoxicity were elucidated in a dopaminergic human neuroblastoma cell line (SH-SY5Y). We evaluated the in vitro effects of benzylpiperazine and benzoylpiperazine on the generation of reactive oxygen species, lipid peroxidation, mitochondrial complex-I activity, catalase activity, superoxide dismutase activity, glutathione content, Bax, caspase-3, Bcl-2 and tyrosine hydroxylase expression. Benzylpiperazine and benzoylpiperazine induced oxidative stress, inhibited mitochondrial functions and stimulated apoptosis. This study provides a germinal assessment of the neurotoxic mechanisms induced by piperazine derivatives that lead to neuronal cell death.

Evaluate the in vitro effect of anthracycline and alkylating cytophosphane chemotherapeutics on dopaminergic neurons.

BACKGROUND: Iatrogenesis is an inevitable global threat to healthcare that drastically increases morbidity and mortality. Cancer is a fatal pathological condition that affects people of different ages, sexes, and races around the world. In addition to the detrimental cancer pathology, one of the most common contraindications and challenges observed in cancer patients is severe adverse drug effects and hypersensitivity reactions induced by chemotherapy. Chemotherapy-induced cognitive neurotoxicity is clinically referred to as Chemotherapy-induced cognitive impairment (CICI), chemobrain, or chemofog. In addition to CICI, chemotherapy also causes neuropsychiatric issues, mental disorders, hyperarousal states, and movement disorders. A synergistic chemotherapy regimen of Doxorubicin (Anthracycline-DOX) and Cyclophosphamide (Alkylating Cytophosphane-CPS) is indicated for the management of various cancers (breast cancer, lymphoma, and leukemia). Nevertheless, there are limited research studies on Doxorubicin and Cyclophosphamide's pharmacodynamic and toxicological effects on dopaminergic neuronal function. AIM: This study evaluated the dopaminergic neurotoxic effects of Doxorubicin and Cyclophosphamide. METHODS AND RESULTS: Doxorubicin and Cyclophosphamide were incubated with dopaminergic (N27) neurons. Neuronal viability was assessed using an MTT assay. The effect of Doxorubicin and Cyclophosphamide on various prooxidants, antioxidants, mitochondrial Complex-I & IV activities, and BAX expression were evaluated by Spectroscopic, Fluorometric, and RT-PCR methods, respectively. Prism-V software (La Jolla, CA, USA) was used for statistical analysis. Chemotherapeutics dose-dependently inhibited the proliferation of the dopaminergic neurons. The dopaminergic neurotoxic mechanism of Doxorubicin and Cyclophosphamide was attributed to a significant increase in prooxidants, a decrease in antioxidants, and augmented apoptosis without affecting mitochondrial function. CONCLUSION: This is one of the first reports that reveal Doxorubicin and Cyclophosphamide induce significant dopaminergic neurotoxicity. Thus, Chemotherapy-induced adverse drug reaction issues substantially persist during and after treatment and sometimes never be completely resolved clinically. Consequently, failure to adopt adequate patient care measures for cancer patients treated with certain chemotherapeutics might substantially raise the incidence of numerous movement disorders.

Biochemical and thermodynamic properties of de novo synthesized urease from Vicia sativa seeds with enhanced industrial applications.

Urease is one of the most significant enzymes in the industry. The objective of this research was to isolate and partially purify urease from Vicia sativa seeds with urease characterization. With a 6.4 % yield, the purification fold was 9.0. By using chromatography, it was determined that the isolated urease had a molecular weight of 55 kDa. The maximum urease activity was found following a 60-s incubation period at 40 °C and pH 8. The activity of urease was significantly boosted by a mean of calcium, barium, DL-dithiothreitol, Na2EDTA, and citrate (16.9, 26.6, 18.6, 13.6, and 31 %), respectively. But nickel and mercury caused inhibitory effects and completely inhibited urease activity, indicating the presence of a thiol (-SH) group in the enzyme active site. The Arrhenius plot was used to analyze the thermodynamic constants of activation, Ea, ΔH*, ΔG*, and ΔS*. The results showed that the values were 30 kJ/mol, 93.14 kJ/mol, 107.17 kJ/mol/K, and -40.80 J/mol/K, respectively. The significance of urease extraction from various sources may contribute to our understanding of the metabolism of urea in plants. The current report has novelty as it explained for the first time the kinetics and thermodynamics of hydrolysis of urea and inactivation of urease from V. sativa seeds.

Novel enhancement of interfacial interaction and properties in biodegradable polymer composites using green chemically treated spent coffee ground microfiller.

This study investigates the potential of utilizing green chemically treated spent coffee grounds (SCGs) as micro biofiller reinforcement in Poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) biopolymer composites. The aim is to assess the impact of varying SCG concentrations (1 %, 3 %, 5 %, and 7 %) on the functional, thermal, mechanical properties and biodegradability of the resulting composites with a PHBV matrix. The samples were produced through melt compounding using a twin-screw extruder and compression molding. The findings indicate successful dispersion and distribution of SCGs microfiller into PHBV. Chemical treatment of SCG microfiller enhanced the interfacial bonding between the SCG and PHBV, evidenced by higher water contact angles of the biopolymer composites. Field Emission Scanning Electron Microscopy (FE-SEM) confirmed the successful interaction of treated SCG microfiller, contributing to enhanced mechanical characteristics. A two-way ANOVA was conducted for statistical analysis. Mass losses observed after burying the materials in natural soil indicated that the composites degraded faster than the pure PHBV polymer suggesting that both composites are biodegradable, particularly at high levels of spent coffee grounds (SCG). Despite the possibility of agglomeration at higher concentrations, SCG incorporation resulted in improved functional properties, positioning the green biopolymer composite as a promising material for sustainable packaging and diverse applications.

Mitochondrial Medicine: A Promising Therapeutic Option Against Various Neurodegenerative Disorders.

Abnormal mitochondrial morphology and metabolic dysfunction have been observed in many neurodegenerative disorders (NDDs). Mitochondrial dysfunction can be caused by aberrant mitochondrial DNA, mutant nuclear proteins that interact with mitochondria directly or indirectly, or for unknown reasons. Since mitochondria play a significant role in neurodegeneration, mitochondriatargeted therapies represent a prosperous direction for the development of novel drug compounds that can be used to treat NDDs. This review gives a brief description of how mitochondrial abnormalities lead to various NDDs such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. We further explore the promising therapeutic effectiveness of mitochondria- directed antioxidants, MitoQ, MitoVitE, MitoPBN, and dimebon. We have also discussed the possibility of mitochondrial gene therapy as a therapeutic option for these NDDs.

Utilization of experimental design in the formulation and optimization of hyaluronic acid-based nanoemulgel loaded with a turmeric-curry leaf oil nanoemulsion for gingivitis.

Numerous problems affect oral health, and intensive research is focused on essential oil-based nanoemulsions that might treat prevent or these problems. Nanoemulsions are delivery systems that enhance the distribution and solubility of lipid medications to targeted locations. Turmeric (Tur)- and curry leaf oil (CrO)-based nanoemulsions (CrO-Tur-self-nanoemulsifying drug delivery systems [SNEDDS]) were developed with the goal of improving oral health and preventing or treating gingivitis. They could be valuable because of their antibacterial and anti-inflammatory capabilities. CrO-Tur-SNEDDS formulations were produced using the response surface Box-Behnken design with different concentrations of CrO (120, 180, and 250 mg), Tur (20, 35, and 50 mg), and Smix 2:1 (400, 500, and 600 mg). The optimized formulation had a bacterial growth inhibition zone of up to 20 mm, droplet size of less than 140 nm, drug-loading efficiency of 93%, and IL-6 serum levels of between 950 ± 10 and 3000 ± 25 U/ml. The optimal formulation, which contained 240 mg of CrO, 42.5 mg of Tur, and 600 mg of Smix 2:1, was created using the acceptable design. Additionally, the best CrO-Tur-SNEDDS formulation was incorporated into a hyaluronic acid gel, and thereafter it had improved ex-vivo transbuccal permeability, sustained in-vitro release of Tur, and large bacterial growth suppression zones. The optimal formulation loaded into an emulgel had lower levels of IL-6 in the serum than the other formulations evaluated in rats. Therefore, this investigation showed that a CrO-Tur-SNEDDS could provide strong protection against gingivitis caused by microbial infections.

Fabrication, assessment, and optimization of alendronate sodium nanoemulsion-based injectable in-situ gel formulation for management of osteoporosis.

Low bone mass, degeneration of bone tissue, and disruption of bone microarchitecture are all symptoms of the disease osteoporosis, which can decrease bone strength and increase the risk of fractures. The main objective of the current study was to use a phospholipid-based phase separation in-situ gel (PPSG) in combination with an alendronate sodium nanoemulsion (ALS-NE) to help prevent bone resorption in rats. The effect of factors such as concentrations of the ALS aqueous solution, surfactant Plurol Oleique CC 497, and Maisine CC oil on nanoemulsion characteristics such as stability index and globular size was investigated using an l-optimal coordinate exchange statistical design. Injectable PPSG with the best nanoemulsion formulation was tested for viscosity, gel strength, water absorption, and in-vitro ALS release. ALS retention in the rats' muscles was measured after 30 days. The droplet size and stability index of the optimal nanoemulsion were 90 ± 2.0 nm and 85 ± 1.9%, respectively. When mixed with water, the optimal ALS-NE-loaded PPSG became viscous and achieved 36 seconds of gel strength, which was adequate for an injectable in-situ formulation. In comparison with the ALS solution-loaded in-situ gel, the newly created optimal ALS-NE-loaded PPSG produced the sustained and regulated release of ALS; hence, a higher percentage of ALS remained in rats' muscles after 30 days. PPSG that has been loaded with an ALS-NE may therefore be a more auspicious, productive, and effective platform for osteoporosis treatment than conventional oral forms.

Tobramycin-loaded nanoparticles of thiolated chitosan for ocular drug delivery: Preparation, mucoadhesion and pharmacokinetic evaluation.

The present work aimed to develop nanoparticles of tobramycin (TRM) using thiolated chitosan (TCS) in order to improve the mucoadhesion, antibacterial effect and pharmacokinetics. The nanoparticles were evaluated for their compatibility, thermal stability, particle size, zeta potential, mucoadhesion, drug release, kinetics of TRM release, corneal permeation, toxicity and ocular irritation. The thiolation of chitosan was confirmed by 1H NMR and FTIR, which showed peaks at 6.6 ppm and 1230 cm-1, respectively. The nanoparticles had a diameter of 73 nm, a negative zeta potential (-21 mV) and a polydispersity index of 0.15. The optimized formulation, NT8, exhibited the highest values of mucoadhesion (7.8 ± 0.541h), drug loading (87.45 ± 1.309%), entrapment efficiency (92.34 ± 2.671%), TRM release (>90%) and corneal permeation (85.56%). The release pattern of TRM from the developed formulations was fickian diffusion. TRM-loaded nanoparticles showed good antibacterial activity against Pseudomonas aeruginosa. The optimized formulation NT8 (0.1% TRM) greatly increased the AUC(0-∞) (1.5-fold) while significantly reducing the clearance (5-fold) compared to 0.3% TRM. Pharmacokinetic parameters indicated improved ocular retention and bioavailability of TRM loaded nanoparticles. Our study demonstrated that the TRM-loaded nanoparticles had improved mucoadhesion and pharmacokinetics and a suitable candidate for effective treatment of ocular bacterial infections.

Enhanced Solubility and Biological Activity of Dexibuprofen-Loaded Silica-Based Ternary Solid Dispersions.

The current study was designed to formulate ternary solid dispersions (TSDs) of dexibuprofen (Dex) by solvent evaporation to augment the solubility and dissolution profile, in turn providing gastric protection and effective anti-inflammatory activity. Initially, nine formulations (S1 to S9) of binary solid dispersions (BSDs) were developed. Formulation S1 comprising a 1:1 weight ratio of Dex and Syloid 244FP® was chosen as the optimum BSD formulation due to its better solubility profile. Afterward, 20 TSD formulations were developed using the optimum BSD. The formulation containing Syloid 244FP® with 40% Gelucire 48/16® (S18) and Poloxamer 188® (S23) successfully enhanced the solubility by 28.23 and 38.02 times, respectively, in pH 6.8, while dissolution was increased by 1.99- and 2.01-fold during the first 5 min as compared to pure drug. The in vivo gastroprotective study in rats suggested that the average gastric lesion index was in the order of pure Dex (8.33 ± 2.02) > S1 (7 ± 1.32) > S18 (2.17 ± 1.61) > S23 (1.83 ± 1.04) > control (0). The in vivo anti-inflammatory study in rats revealed that the percentage inhibition of swelling was in the order of S23 (71.47 ± 2.16) > S18 (64.8 ± 3.79) > S1 (54.14 ± 6.78) > pure drug (18.43 ± 2.21) > control (1.18 ± 0.64) after 6 h. ELISA results further confirmed the anti-inflammatory potential of the developed formulation, where low levels of IL-6 and TNF alpha were reported for animals treated with S23. Therefore, S23 could be considered an effective formulation that not only enhanced the solubility and bioavailability but also reduced the gastric irritation of Dex.

Abelmoschus eculentus Seed Extract Exhibits In Vitro and In Vivo Anti-Alzheimer's Potential Supported by Metabolomic and Computational Investigation.

Abelmoschus esculentus Linn. (okra, F. Malvaceae) is a fruit widely consumed all over the world. In our study, the anti-Alzheimer's potential of A. esculentus was evaluated. An in vitro DPPH free radical assay on A. esculentus seed's total extract and AChE inhibition potential screening indicated a significant anti-Alzheimer's activity of the extract, which was confirmed through an in vivo study in an aluminum-intoxicated rat model. Additionally, in vivo results demonstrated significant improvement in Alzheimer's rats, which was confirmed by improving T-maze, beam balance tests, lower serum levels of AChE, norepinephrine, glycated end products, IL-6, and MDA. The levels of dopamine, BDNF, GSH, and TAC returned to normal values during the study. Moreover, histological investigations of brain tissue revealed that the destruction in collagen fiber nearly returns back to the normal pattern. Metabolomic analysis of the ethanolic extract of A. esculentus seeds via LC-HR-ESI-MS dereplicated ten compounds. A network pharmacology study displayed the relation between identified compounds and 136 genes, among which 84 genes related to Alzheimer's disorders, and focused on AChE, APP, BACE1, MAPT and TNF genes with interactions to all Alzheimer's disorders. Consequently, the results revealed in our study grant potential dietary elements for the management of Alzheimer's disorders.

Tailoring and optimization of a honey-based nanoemulgel loaded with an itraconazole-thyme oil nanoemulsion for oral candidiasis.

The use of essential oil-based nanoemulsions (NEs) has been the subject of extensive research on a variety of conditions affecting the oral cavity. NEs are delivery methods that improve the solubility and distribution of lipid medicines to the intended areas. Because of their antibacterial and antifungal properties, itraconazole and thyme oil-based self-nanoemulsifying drug delivery systems (ItZ-ThO-SNEDDS) were created to protect oral health against oral microorganisms. The ItZ-ThO-SNEDDS were created utilizing an extreme verices mixture design, and varying concentrations of ThO (10% and 25%), labrasol (40% and 70%), and transcutol (20% and 40%) were used. The ItZ-ThO-SNEDDS had droplet sizes of less than 250 nm, a drug-loading efficiency of up to 64%, and a fungal growth inhibition zone of up to 20 mm. The accepted design was used to obtain the ideal formulation, which contained ThO in the amount of 0.18 g/ml, labrasol 0.62 g/ml, and transcutol 0.2 g/ml. The best ItZ-ThO-SNEDDS formulation was incorporated into a honey-based gel, which demonstrated improved release of ItZ in vitro and improved transbuccal permeation ex vivo. In addition, when compared with various formulations tested in rats, the optimized loaded emulgel decreased the ulcer index. This study therefore demonstrated that the ItZ-ThO-SNEDDS could offer an effective defense against oral diseases caused by microbial infections.

Cardioprotective Effects of Oroxylum indicum Extract Against Doxorubicin and Cyclophosphamide-Induced Cardiotoxicity.

Administration of Chemotherapeutics, especially doxorubicin (DOX) and cyclophosphamide (CPS), is commonly associated with adverse effects such as myelosuppression and cardiotoxicity. At this time, few approved therapeutic options are currently available for the management of chemotherapy-associated cardiotoxicity. Thus, identification of novel therapeutics with potent cardioprotective properties and minimal adverse effects are pertinent in treating Doxorubicin and Cyclophosphamide-induced cardiotoxicity. Oroxylum indicum extract (OIE, Sabroxy®) is a natural product known to possess several beneficial biological functions including antioxidant, anti-inflammatory and cytoprotective effects. We therefore set to investigate the cardioprotective effects of OIE against Doxorubicin and Cyclophosphamide-induced cardiotoxicity and explore the potential cardioprotective mechanisms involved. Adult male mice were treated with DOX and CPS in combination, OIE alone, or a combination of OIE and DOX & CPS. Swimming test was performed to assess cardiac function. Markers of oxidative stress were assessed by levels of reactive oxygen species (ROS), nitrite, hydrogen peroxide, catalase, and glutathione content. The activity of interleukin converting enzyme and cyclooxygenase was determined as markers of inflammation. Mitochondrial function was assessed by measuring Complex-I activity. Apoptosis was assessed by Caspase-3 and protease activity. Mice treated with DOX and CPS exhibited reduced swim rate, increased oxidative stress, increased inflammation, and apoptosis in the heart tissue. These cardiotoxic effects were significantly reduced by co-administration of OIE. Furthermore, computational molecular docking studies revealed potential binding of DOX and CPS to tyrosine hydroxylase which validated our in vivo findings regarding the inhibition of tyrosine hydroxylase activity. Our current findings indicated that OIE counteracts Doxorubicin and Cyclophosphamide-induced cardiotoxicity-through inhibition of ROS-mediated apoptosis and by blocking the effect on tyrosine hydroxylase. Taken together, our findings suggested that OIE possesses cardioprotective effects to counteract potentially fatal cardiac complications associated with chemotherapy treatment.

Response Surface Methodology (RSM) Powered Formulation Development, Optimization and Evaluation of Thiolated Based Mucoadhesive Nanocrystals for Local Delivery of Simvastatin.

In oral administration systems, mucoadhesive polymers are crucial for drug localization and target-specific activities. The current work focuses on the application of thiolated xanthan gum (TXG) to develop and characterize a novel mucoadhesive nanocrystal (NC) system of simvastatin (SIM). Preparation of SIM-NC was optimized using response surface methodology (RSM) coupled with statistical applications. The concentration of Pluronic F-127 and vacuum pressure were optimized by central composite design. Based on this desirable approach, the prerequisites of the optimum formulation can be achieved by a formulation having 92.568 mg of F-127 and 77.85 mbar vacuum pressure to result in EE of 88.8747% and PS of 0.137.835 nm. An optimized formulation was prepared with the above conditions along with xanthan gum (XG) and TXG and various parameters were evaluated. A formulation containing TXG showed 98.25% of SIM at the end of 96 h. Regarding the mucoadhesion potential evaluated by measuring zeta potential, TXG-SIM-NC shoed the maximum zeta potential of 16,455.8 ± 869 mV at the end of 6 h. The cell viability percentage of TXG-SIM-NC (52.54 ± 3.4% with concentration of 50 µg/mL) was less than the plain SIM, with XG-SIM-NC showing the highest cytotoxicity on HSC-3 cells. In vivo pharmacokinetic studies confirm the enhanced bioavailability of formulated mucoadhesive systems of SIM-NC, with TXG-SIM-NC exhibiting the maximum.

In Vitro and In Vivo Evaluation of Hydroxypropyl-ß-cyclodextrin-grafted-poly(acrylic acid)/poly(vinyl pyrrolidone) Semi-Interpenetrating Matrices of Dexamethasone Sodium Phosphate.

In this paper, we fabricated semi-interpenetrating polymeric network (semi-IPN) of hydroxypropyl-ß-cyclodextrin-grafted-poly(acrylic acid)/poly(vinyl pyrrolidone) (HP-ß-CD-g-poly(AA)/PVP) by the free radical polymerization technique, intended for colon specific release of dexamethasone sodium phosphate (DSP). Different proportions of polyvinyl pyrrolidone (PVP), acrylic acid (AA), and hydroxypropyl-beta-cyclodextrin (HP-ß-CD) were reacted along with ammonium persulphate (APS) as initiator and methylene-bis-acrylamide (MBA) as crosslinker to develop a hydrogel system with optimum swelling at distal intestinal pH. Initially, all formulations were screened for swelling behavior and AP-8 was chosen as optimum formulation. This formulation was capable of releasing a small amount of drug at acidic pH (1.2), while a maximum amount of drug was released at colonic pH (7.4) by the non-Fickian diffusion mechanism. Fourier transformed infrared spectroscopy (FTIR) revealed successful grafting of components and development of semi-IPN structure without any interaction with DSP. Thermogravimetric analysis (TGA) confirmed the thermal stability of developed semi-IPN. X-ray diffraction (XRD) revealed reduction in crystallinity of DSP upon loading in the hydrogel. The scanning electron microscopic (SEM) images revealed a rough and porous hydrogel surface. The toxicological evaluation of semi-IPN hydrogels confirmed their bio-safety and hemocompatibility. Therefore, the prepared hydrogels were pH sensitive, biocompatible, showed good swelling, mechanical properties, and were efficient in releasing the drug in the colonic environment. Therefore, AP-8 can be deemed as a potential carrier for targeted delivery of DSP to treat inflammatory bowel diseases.

Electrospun Nanofiber Composites for Drug Delivery: A Review on Current Progresses.

A medication's approximate release profile should be sustained in order to generate the desired therapeutic effect. The drug's release site, duration, and rate must all be adjusted to the drug's therapeutic aim. However, when designing drug delivery systems, this may be a considerable hurdle. Electrospinning is a promising method of creating a nanofibrous membrane since it enables drugs to be placed in the nanofiber composite and released over time. Nanofiber composites designed through electrospinning for drug release purposes are commonly constructed of simple structures. This nanofiber composite produces matrices with nanoscale fiber structure, large surface area to volume ratio, and a high porosity with small pore size. The nanofiber composite's large surface area to volume ratio can aid with cell binding and multiplication, drug loading, and mass transfer processes. The nanofiber composite acts as a container for drugs that can be customized to a wide range of drug release kinetics. Drugs may be electrospun after being dissolved or dispersed in the polymer solution, or they can be physically or chemically bound to the nanofiber surface. The composition and internal structure of the nanofibers are crucial for medicine release patterns.