Statistical design and optimization of nano-transfersomes based chitosan gel for transdermal delivery of cefepime.

OBJECTIVES: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel. METHODS: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed. RESULTS: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery. CONCLUSION: This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.

Anabasis articulata (Forssk.) Moq: A Good Source of Phytochemicals with Antibacterial, Antioxidant, and Antidiabetic Potential.

Anabasis articulata is medicinally used to treat various diseases. In this study, A. articulata was initially subjected to extraction, and the resultant extracts were then evaluated for their antimicrobial, antioxidant, and antidiabetic potentials. After obtaining the methanolic extract, it was subjected to a silica gel column for separation, and fractions were collected at equal intervals. Out of the obtained fractions (most rich in bioactive compounds confirmed through HPLC), designated as A, B, C, and D as well hexane fraction, were subjected to GC-MS analysis, and a number of valuable bioactive compounds were identified from the chromatograms. The preliminary phytochemical tests were positive for the extracts where fraction A exhibited the highest total phenolic and flavonoid contents. The hexane fraction as antimicrobial agent was the most potent, followed by the crude extract, fraction A, and fraction D. DPPH and ABTS assays were used to estimate the free radical scavenging potential of the extracts. Fraction C was found to contain potent inhibitors of both the tested radicals, followed by fraction D. The potential antidiabetic extracts were determined using α-glucosidase and amylase as probe enzymes. The former was inhibited by crude extract, hexane, and A, B, C and D fractions to the extent of 85.32 ± 0.20, 61.14 ± 0.49, 62.15 ± 0.84, 78.51 ± 0.45, 72.57 ± 0.92 and 70.61 ± 0.91%, respectively, at the highest tested concentration of 1000 µg/mL with their IC50 values 32, 180, 200, 60, 120 and 140 µg/mL correspondingly, whereas α-amylase was inhibited to the extent of 83.98 ± 0.21, 58.14 ± 0.75, 59.34 ± 0.89, 81.32 ± 0.09, 74.52 ± 0.13 and 72.51 ± 0.02% (IC50 values; 34, 220, 240, 58, 180, and 200 µg/mL, respectively). The observed biological potentials might be due to high phenolic and flavonoid content as detected in the extracts. The A. articulata might thus be considered an efficient therapeutic candidate and could further be investigated for other biological potentials along with the isolation of pure responsible ingredients.

Efficacy of 2-Hydroxyflavanone in Rodent Models of Pain and Inflammation: Involvement of Opioidergic and GABAergic Anti-Nociceptive Mechanisms.

The current work examined the pharmacological potential of a selected flavanone derivative 2-hydroxyflavanone as a promising remedy for the treatment and management of pain. The selected flavanone derivative (2-HF) was evaluated for its analgesic and anti-inflammatory potentials following standard pharmacological protocols including hot plate, acetic acid-induced writhing and tail immersion tests. Naloxone and pentylenetetrazol were used to evaluate the potential implication of GABAergic and opioidergic mechanisms. The anti-inflammatory potential of 2-HF was confirmed using carrageenan-, serotonin- and histamine-induced paw edema models as well as a xylene-induced ear edema model. Furthermore, the anti-neuropathic potential of 2-HF was tested using a cisplatin-induced neuropathic pain model. Our sample, at the tested concentrations of 15, 30 and 45 mg kg-1, showed considerable analgesic, anti-inflammatory effects, as well as efficacy against neuropathic pain. Naloxone and pentylenetetrazol at 1 and 15 mg kg-1 antagonized the anti-nociceptive activities of 2-hydroxyflavanone indicating the involvement of opioidergic and GABAergic mechanisms. In the static allodynia model, combination of gabapentin 75 mg kg-1 with 2-HF at 15, 30, 45 mg kg-1 doses exhibited considerable efficacy. In cold allodynia, 2-hydroxyflavanone, at doses of 15, 30 and 45 mg kg-1 and in combination with gabapentin (75 mg kg-1), demonstrated prominent anti-allodynic effects. The paw withdrawal latency was considerably increased in gabapentin + cisplatin treated groups. Moreover, cisplatin + 2-hydroxyflavanone 15, 30, 45 mg kg-1 showed increases in paw withdrawal latency. Likewise, considerable efficacy was observed for 2-hydroxyflavanone in thermal hyperalgesia and dynamic allodynia models. Our findings suggest that 2-hydroxyflavanone is a potential remedy for pain syndrome, possibly mediated through opioidergic and GABAergic mechanisms.

Formulation and Characterization of Chitosan-Decorated Multiple Nanoemulsion for Topical Delivery In Vitro and Ex Vivo.

In the present study, chitosan-decorated multiple nanoemulsion (MNE) was formulated using a two-step emulsification process. The formulated multiple nanoemuslion was evaluated physiochemically for its size and zeta potential, surface morphology, creaming and cracking, viscosity and pH. A Franz diffusion cell apparatus was used to carry out in vitro drug-release and permeation studies. The formulated nanoemulsion showed uniform droplet size and zeta potential. The pH and viscosity of the formulated emulsion were in the range of and suitable for topical delivery. The drug contents of the simple nanoemulsion (SNE), the chitosan-decorated nanoemulsion (CNE) and the MNE were 71 ± 2%, 82 ± 2% and 90 ± 2%, respectively. The formulated MNE showed controlled release of itraconazole as compared with that of the SNE and CNE. This was attributed to the chitosan decoration as well as to formulating multiple emulsions. The significant permeation and skin drug retention profile of the MNE were attributed to using the surfactants tween 80 and span 20 and the co-surfactant PEG 400. ATR-FTIR analysis confirmed that the MNE mainly affects the lipids and proteins of the skin, particularly the stratum corneum, which results in significantly higher permeation and retention of the drug. It was concluded that the proposed MNE formulation delivers drug to the target site of the skin and can be therapeutically used for various cutaneous fungal infections.

Biological Evaluation, Phytochemical Screening, and Fabrication of Indigofera Linifolia Leaves Extract-Loaded Nanoparticles.

Indigofera linifolia is a medicinally important plant, and by virtue of its rich phytochemical composition, this plant is widely used as essential component in traditional medication systems. Due to its wide range of medicinal applications, the extract-loaded chitosan (Ext+Ch), extract-loaded PEG (Ext+PEG), and extract-loaded locust bean gum (Ext+LGB) nanoparticles (NPs) were prepared in the present study. The prepared NPs were then evaluated for their antibacterial, antioxidant, and antidiabetic potentials. Antibacterial activities of the crude extract and the synthesized NPs were performed following standard procedures reported in the literature. The antioxidant capabilities of extract and NPs were evaluated using DPPH free radical scavenging assay. The antidiabetic potential of the samples was evaluated against α-amylase and α-glucosidase. Ext+PEG NPs showed more potent antibacterial activity against the selected strains of bacteria with the highest activity against Escherichia coli. The lowest antibacterial potential was observed for Ext+LGB NPs. The Ext+LGB NPs IC50 value of 39 µg/mL was found to be the most potent inhibitor of DPPH free radicals. Ext+LGB NPs showed a greater extent of inhibition against α-glucosidase and α-amylase with an IC50 of 83 and 78 µg/mL, whereas for the standard acarbose the IC50 values recorded against the mentioned enzymes were 69 and 74 µg/mL, respectively. A high concentration of phenolics and flavonoids in the crude extract was confirmed through TPC and TFC tests, HPLC profiling, and GC-MS analysis. It was considered that the observed antibacterial, antidiabetic, and antioxidant potential might be due the presence of these phenolics and flavonoids detected. The plant could thus be considered as a potential candidate to be used as a remedy of the mentioned health complications. However, further research in this regard is needed to isolate the exact responsible compounds of the observed biological potentials exhibited by the crude extract. Further, toxicity and pharmacological evaluations in animal models are also needed to establish the safety or toxicity profile of the plant.

The Therapeutic Application of Tamarix aphylla Extract Loaded Nanoemulsion Cream for Acid-Burn Wound Healing and Skin Regeneration.

Background and Objectives: Nanomedicine is a constantly growing field for the diagnosis and treatment of various diseases as well as for regenerative therapy. Nanotechnology-based drug-delivery systems improve pharmacological and pharmacokinetic profiles of plants based biologically active molecules. Based on traditional claims, leaves of the Tamarix aphylla (TA) were investigated for their potential healing activity on burn wounds. Materials and Methods: In this study, TA-based nanoemulsion was prepared. The nanoemulsion was characterized for size, zeta potential, pH, viscosity, and stability. The nanoemulsion containing plant extract was converted into cream and evaluated for its efficacy against acid-burn wounds inflicted in the dorsum of rabbits. The animals were classified into four main groups: Group A as a normal control group, Group B as a positive control (treated with cream base + silver sulfadiazine), Group C as a standard drug (silver sulfadiazine), and Group D as a tested (treated with nanoemulsion cream containing TA extract). The prepared system could deliver TA to the target site and was able to produce pharmacological effects. On days 0, 7, 14, 21, 28, and 35, wound contraction rate was used to determine healing efficacy. The wound samples were collected from the skin for histological examination. Results: Based on statistical analysis using wound-healing time, Group D showed a shorter period (21.60 ± 0.5098) (p < 0.01) than the average healing time of Group C (27.40 ± 0.6002) (p < 0.05) and Group B (33.40 ± 0.8126) (p < 0.05). The histopathological assessment showed that burn healing was better in Group D compared with Group C and Group B. The nanoemulsion cream had a non-sticky texture, low viscosity, excellent skin sensations, and a porous structure. By forming a protective layer on the skin and improving moisture, it enhanced the condition of burnt skin. Conclusions: According to the findings of this study, nanoemulsion cream containing TA extract has great potential in healing acid-burn wounds

GPS Trajectory Completion Using End-to-End Bidirectional Convolutional Recurrent Encoder-Decoder Architecture with Attention Mechanism.

GPS datasets in the big data regime provide rich contextual information that enable efficient implementation of advanced features such as navigation, tracking, and security in urban computing systems. Understanding the hidden patterns in large amount of GPS data is critically important in ubiquitous computing. The quality of GPS data is the fundamental key problem to produce high quality results. In real world applications, certain GPS trajectories are sparse and incomplete; this increases the complexity of inference algorithms. Few of existing studies have tried to address this problem using complicated algorithms that are based on conventional heuristics; this requires extensive domain knowledge of underlying applications. Our contribution in this paper are two-fold. First, we proposed deep learning based bidirectional convolutional recurrent encoder-decoder architecture to generate the missing points of GPS trajectories over occupancy grid-map. Second, we interfaced attention mechanism between enconder and decoder, that further enhance the performance of our model. We have performed the experiments on widely used Microsoft geolife trajectory dataset, and perform the experiments over multiple level of grid resolutions and multiple lengths of missing GPS segments. Our proposed model achieved better results in terms of average displacement error as compared to the state-of-the-art benchmark methods.

In Vitro Investigation of Influences of Chitosan Nanoparticles on Fluorescein Permeation into Alveolar Macrophages.

PURPOSE: Pulmonary infection namely tuberculosis is characterized by alveolar macrophages harboring a large microbe population. The chitosan nanoparticles exhibit fast extracellular drug release in aqueous biological milieu. This study investigated the matrix effects of chitosan nanoparticles on extracellular drug diffusion into macrophages. METHODS: Oligo, low, medium and high molecular weight chitosan nanoparticles were prepared by nanospray drying technique. These nanoparticles were incubated with alveolar macrophages in vitro and had model drug sodium fluorescein added into the same cell culture. The diffusion characteristics of sodium fluorescein and nanoparticle behavior were investigated using fluorescence microscopy, scanning electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy techniques. RESULTS: The oligochitosan nanoparticles enabled macrophage membrane fluidization with the extent of sodium fluorescein entry into macrophages being directly governed by the nanoparticle loading. Using nanoparticles made of higher molecular weight chitosan, sodium fluorescein permeation into macrophages was delayed due to viscous chitosan diffusion barrier at membrane boundary. CONCLUSION: Macrophage-chitosan nanoparticle interaction at membrane interface dictates drug migration into cellular domains.

A simple and rapid approach to evaluate the in vitro in vivo role of release controlling agent ethyl cellulose ether derivative polymer.

Diclofenac sodium (DCL-Na) conventional oral tablets exhibit serious side effects when given for a longer period leading to noncompliance. Controlled release matrix tablets of diclofenac sodium were formulated using simple blending (F-1), solvent evaporation (F-2) and co-precipitation techniques (F-3). Ethocel® Standard 7 FP Premium Polymer (15%) was used as a release controlling agent. Drug release study was conducted in 7.4 pH phosphate buffer solutions as dissolution medium in vitro. Pharmacokinetic parameters were evaluated using albino rabbits. Solvent evaporation technique was found to be the best release controlling technique thereby prolonging the release rate up to 24 hours. Accelerated stability studies of the optimized test formulation (F-2) did not show any significant change (p<0.05) in the physicochemical characteristics and release rate when stored for six months. A simple and rapid method was developed for DCL-Na active moiety using HPLC-UV at 276nm. The optimized test tablets (F-2) significantly (p<0.05) exhibited peaks plasma concentration (cmax=237.66±1.98) and extended the peak time (tmax=4.63±0.24). Good in-vitro in vivo correlation was found (R(2)=0.9883) against drug absorption and drug release. The study showed that once-daily controlled release matrix tablets of DCL-Na were successfully developed using Ethocel® Standard 7 FP Premium.

Neuroprotective potentials of Lead phytochemicals against Alzheimer's disease with focus on oxidative stress-mediated signaling pathways: Pharmacokinetic challenges, target specificity, clinical trials and future perspectives.

BACKGROUND: Alzheimer's diseases (AD) and dementia are among the highly prevalent neurological disorders characterized by deposition of beta amyloid (Aß) plaques, dense deposits of highly phosphorylated tau proteins, insufficiency of acetylcholine (ACh) and imbalance in glutamatergic system. Patients typically experience cognitive, behavioral alterations and are unable to perform their routine activities. Evidence also suggests that inflammatory processes including excessive microglia activation, high expression of inflammatory cytokines and release of free radicals. Thus, targeting inflammatory pathways beside other targets might be the key factors to control- disease symptoms and progression. PURPOSE: This review is aimed to highlight the mechanisms and pathways involved in the neuroprotective potentials of lead phytochemicals. Further to provide updates regarding challenges associated with their use and their progress into clinical trials as potential lead compounds. METHODS: Most recent scientific literature on pre-clinical and clinical data published in quality journals especially on the lead phytochemicals including curcumin, catechins, quercetin, resveratrol, genistein and apigenin was collected using SciFinder, PubMed, Google Scholar, Web of Science, JSTOR, EBSCO, Scopus and other related web sources. RESULTS: Literature review indicated that the drug discovery against AD is insufficient and only few drugs are clinically approved which have limited efficacy. Among the therapeutic options, natural products have got tremendous attraction owing to their molecular diversity, their safety and efficacy. Research suggest that natural products can delay the disease onset, reduce its progression and regenerate the damage via their anti-amyloid, anti-inflammatory and antioxidant potentials. These agents regulate the pathways involved in the release of neurotrophins which are implicated in neuronal survival and function. Highly potential lead phytochemicals including curcumin, catechins, quercetin, resveratrol, genistein and apigenin regulate neuroprotective signaling pathways implicated in neurotrophins-mediated activation of tropomyosin receptor kinase (Trk) and p75 neurotrophins receptor (p75NTR) family receptors. CONCLUSIONS: Phytochemicals especially phenolic compounds were identified as highly potential molecules which ameliorate oxidative stress induced neurodegeneration, reduce Aß load and inhibit vital enzymes. Yet their clinical efficacy and bioavailability are the major challenges which need further interventions for more effective therapeutic outcomes.

Formulation and in vitro evaluation of clotrimazole gel containing almond oil and tween 80 as penetration enhancer for topical application.

Achieving a desirable percutaneous absorption of drug molecule is a major concern in formulating dermal and transdermal products. The use of penetration enhancers could provide a successful mean for this purpose. The aim of this study was to develop Clotrimazole gel and to evaluate the effect of almond oil and tween 80 (in different concentrations), on the permeation of drug through rabbit skin in vitro. In order to investigate the effect of penetration enhancers used in this study on the permeation of Clotrimazole through sections of excised rabbit skin, Franz diffusion cell was employed. Sample solution was withdrawn at specific time interval up to 24 h. Significant difference in permeation among the eight formulations was seen in the study. The permeation profile of various formulations also showed that the added enhancers in individual batches affected the permeation of the drug. Drug permeation increased with increased concentration of Tween 80 and decreased concentration of almond oil. Furthermore, almond oil combined with tween 80 showed synergistic effect. The clotrimazole gels were successfully formulated and could be beneficial for topical use.

Assesment of polyphenolic compounds against biofilms produced by clinical Acinetobacter baumannii strains using in silico and in vitro models.

Several types of microbial infections are caused by Acinetobacter baumanii that has developed resistance to antimicrobial agents. We therefore investigated the role of plant polyphenols against A. baumannii using in silico and in vitro models. The clinical strains of A. baumannii were investigated for determination of resistance pattern and resistance mechanisms including efflux pump, extended spectrum beta lactamase, phenotype detection of AmpC production, and Metallo-ß-lactamase. The polyphenolic compounds were docked against transcription regulator BfmR (PDB ID 6BR7) and antimicrobial, antibiofilm, and anti-quorum sensing activities were performed. The antibiogram studies showed that all isolated strains were resistant. Strain A77 was positive in Metallo-ß-lactamase production. Similarly, none of strains were producers of AmpC, however, A77, A76, A75 had active efflux pumps. Molecular docking studies confirmed a strong binding affinity of Rutin and Catechin towards transcription regulator 6BR7. A significant antimicrobial activity was recorded in case of quercetin and syringic acid (MIC 3.1 µg/mL) followed by vanillic acid and caffeic acid (MIC 12.5 µg/mL). All tested compounds presented a strong antibiofilm activity against A. baumanii strain A77 (65 to 90%). It was concluded that all tested polyphenols samples posess antimicrobial and antibiofilm activities, and hence they may be utilized to treat multidrug resistance A. baumannii infections.

Fabrication of Novel Omeprazole-Based Chitosan Coated Nanoemulgel Formulation for Potential Anti-Microbia; In Vitro and Ex Vivo Characterizations.

Infectious diseases remain inevitable factors for high mortality and morbidity rate in the modern world to date. Repurposing is a novel approach to drug development has become an intriguing research topic in the literature. Omeprazole is one of the top ten proton pump inhibitors prescribed in the USA. The literature suggests that no reports based on omeprazole anti-microbial actions have been discovered to date. This study entails the potential of omeprazole to treat skin and soft tissue infections based on the literature's evident anti-microbial effects. To get a skin-friendly formulation, a chitosan-coated omeprazole-loaded nanoemulgel formulation was fabricated using olive oil, carbopol 940, Tween 80, Span 80, and triethanolamine by high-speed homogenization technique. The optimized formulation was physicochemically characterized for zeta potential, size distribution, pH, drug content, entrapment efficiency, viscosity, spreadability, extrudability, in-vitro drug release, ex-vivo permeation analysis, and minimum inhibitory concentration determination. The FTIR analysis indicated that there was no incompatibility between the drug and formulation excipients. The optimized formulation exhibited particle size, PDI, zeta potential, drug content, and entrapment efficiency of 369.7 ± 8.77 nm, 0.316, -15.3 ± 6.7 mV, 90.92 ± 1.37% and 78.23 ± 3.76%, respectively. In-vitro release and ex-vivo permeation data of optimized formulation showed 82.16% and 72.21 ± 1.71 µg/cm2, respectively. The results of minimum inhibitory concentration (1.25 mg/mL) against selected bacterial strains were satisfactory, suggesting a successful treatment approach for the topical application of omeprazole to treat microbial infections. Furthermore, chitosan coating synergistically increases the antibacterial activity of the drug.

Fabrication of Polymeric Hydrogels Containing Esomeprazole for Oral Delivery: In Vitro and In Vivo Pharmacokinetic Characterization.

Hydrogel is one of the most interesting and excellent candidates for oral drug delivery. The current study focuses on formulation development of hydrogels for controlled oral delivery of esomeprazole. The hydrogels were prepared by solution casting method by dissolving polymers in Polyvinyl alcohol (PVA) solution. Calcium alginate, Hydroxyl propyl methylcellulose (HPMC), acrylic acid and chondroitin sulfate were used in the preparation of hydrogels. Fourier transform infrared (FTIR) analysis showed no incompatibilities between drug and excipients used in the preparation of formulations. The hydrogels were characterized for size and surface morphology. Drug encapsulation efficiency was measured by Ultraviolet-visible (UV-VIS) spectroscopy. In vitro release studies were carried out using dissolution apparatus. The formulated hydrogels were then compared with the marketed product in vivo using rabbits. The result indicates that prepared hydrogels have a uniform size with a porous surface. The esomeprazole encapsulation efficiency of the prepared hydrogels was found to be 83.1 ± 2.16%. The esomeprazole-loaded hydrogel formulations showed optimum and Pharmacopeial acceptable range swelling behavior. The release of esomeprazole is controlled for 24 h (85.43 ± 0.32% in 24 h). The swelling and release of drug results make the prepared hydrogels a potential candidate for the controlled delivery of esomeprazole. The release of the drug from prepared hydrogel followed the super case transport-2 mechanism. The in vivo studies showed that prepared hydrogel formulations showed controlled and prolonged release of esomeprazole as compared to drug solution and marketed product. The formulations were kept for stability studies; there was no significant change observed in physical parameters, i.e., (appearance, color change and grittiness) at 40 °C ± 2/75% ± RH. There was a negligible difference in the drug content observed after the stability study suggested that all the formulations are stable under the given conditions for 60 days. The current study provides a valuable perspective on the controlled release profile of Hydroxyl propyl methylcellulose (HPMC) and calcium alginate-based esomeprazole hydrogels.

Formulation and Characterization of Ethyl Cellulose-Based Patches Containing Curcumin-Chitosan Nanoparticles for the Possible Management of Inflammation via Skin Delivery.

Curcumin, a natural phenolic compound, exhibits poor absorption and extensive first pass metabolism after oral administration. In the present study, curcumin-chitosan nanoparticles (cur-cs-np) were prepared and incorporated into ethyl cellulose patches for the management of inflammation via skin delivery. Ionic gelation method was used for the preparation of nanoparticles. The prepared nanoparticles were evaluated for size, zetapotential, surface morphology, drug content, and % encapsulation efficiency. The nanoparticles were then incorporated into ethyl cellulose-based patches using solvent evaporation technique. ATR-FTIR was used to study/assess incompatibility between drug and excipients. The prepared patches were evaluated physiochemically. The in vitro release, ex vivo permeation, and skin drug retention studies were carried out using Franz diffusion cells and rat skin as permeable membrane. The prepared nanoparticles were spherical, with particle size in the range of 203-229 nm, zetapotential 25-36 mV, and PDI 0.27-0.29 Mw/Mn. The drug content and %EE were 53% and 59%. Nanoparticles incorporated patches are smooth, flexible, and homogenous. The in vitro release and ex vivo permeation of curcumin from nanoparticles were higher than the patches, whereas the skin retention of curcumin was significantly higher in case of patches. The developed patches deliver cur-cs-np into the skin, where nanoparticles interact with skin negative charges and hence result in higher and prolonged retention in the skin. The higher concentration of drug in the skin helps in better management of inflammation. This was shown by anti-inflammatory activity. The inflammation (volume of paw) was significantly reduced when using patches as compared to nanoparticles. It was concluded that the incorporation of cur-cs-np into ethyl cellulose-based patches results in controlled release and hence enhanced anti-inflammatory activity.

Clarithromycin and Pantoprazole Gastro-Retentive Floating Bilayer Tablet for the Treatment of Helicobacter Pylori: Formulation and Characterization.

Bilayer/multilayer tablets have been introduced to formulate incompatible components for compound preparations, but they are now more commonly used to tailor drug release. This research aimed to formulate a novel gastro-retentive tablet to deliver a combination of a fixed dose of two drugs to eliminate Helicobacter pylori (H. pylori) in the gastrointestinal tract. The bilayer tablets were prepared by means of the direct compression technique. The controlled-release bilayer tablets were prepared using various hydrophilic swellable polymers (sodium alginate, chitosan, and HPMC-K15M) alone and in combination to investigate the percent of swelling behavior and average drug release. The weight of the controlled-release floating layer was 500 mg, whereas the weight of the floating tablets of pantoprazole was 100 mg. To develop the most-effective formulation, the effects of the experimental components on the floating lag time, the total floating time, T 50%, and the amount of drug release were investigated. The drugs' and excipients' compatibilities were evaluated using ATR-FTIR and DSC. Pre-compression and post-compression testing were carried out for the prepared tablets, and they were subjected to in vitro characterization studies. The pantoprazole layer of the prepared tablet demonstrated drug release (95%) in 2 h, whereas clarithromycin demonstrated sustained drug release (83%) for up to 24 h (F7). The present study concluded that the combination of sodium alginate, chitosan, and HPMC polymers (1:1:1) resulted in a gastro-retentive and controlled-release drug delivery system of the drug combination. Thus, the formulation of the floating bilayer tablets successfully resulted in a biphasic drug release. Moreover, the formulation (F7) offered the combination of two drugs in a single-tablet formulation containing various polymers (sodium alginate, chitosan, and HPMC polymers) as the best treatment option for local infections such as gastric ulcers.

Physicochemical and nanomedicine applications of phyto-reduced erbium oxide (Er2O3) nanoparticles.

Hyphaene thebaica fruits were used for the fabrication of spherical erbium oxide nanoparticles (HT-Er2O3 NPS) using a one-step simple bioreduction process. XRD pattern revealed a highly crystalline and pure phase with crystallite size of ~ 7.5 nm, whereas, the W-H plot revealed crystallite size of 11 nm. FTIR spectra revealed characteristic Er-O atomic vibrations in the fingerprint region. Bandgap was obtained as 5.25 eV using K-M function. The physicochemical and morphological nature was established using Raman spectroscopy, reflectance spectroscopy, SAED and HR-TEM. HT-Er2O3 NPS were further evaluated for antidiabetic potential in mice using in-vivo and in-vitro bioassays. The synthesized HT-Er2O3 NPS were screened for in vitro anti-diabetic potentials against α-glucosidase enzyme and α-amylase enzyme and their antioxidant potential was evaluated using DPPH free radical assay. A dose dependent inhibition was obtained against α-glucosidase (IC50 12 µg/mL) and α-amylase (IC50 78 µg/mL) while good DPPH free radical scavenging potential (IC50 78 µg mL-1) is reported. At 1000 µg/mL, the HT-Er2O3 NPS revealed 90.30% and 92.30% inhibition of α-amylase and α-glucosidase enzymes. HT-Er2O3 NPs treated groups were observed to have better glycemic control in diabetic animals (503.66 ± 5.92*** on day 0 and 185.66 ± 2.60*** on day 21) when compared with positive control glibenclamide treated group. Further, HT-Er2O3 NPS therapy for 21 days caused a considerable effect on serum total lipids, cholesterol, triglycerides, HDL and LDL as compared to untreated diabetic group. In conclusion, our preliminary findings on HT-Er2O3 NPS revealed considerable antidiabetic potential and thus can be an effective candidate for controlling the post-prandial hyperglycemia. However, further studies are encouraged especially taking into consideration the toxicity aspects of the nanomaterial.

Synthesis and Characterization of Sulfur Nanoparticles of Citrus limon Extract Embedded in Nanohydrogel Formulation: In Vitro and In Vivo Studies.

The study aimed to synthesize non-noxious, clean, reliable, and green sulfur nanoparticles (SNPs) from Citrus limon leaves. The synthesized SNPs were used to analyze particle size, zeta potential, UV-visible spectroscopy, SEM, and ATR-FTIR. The prepared SNPs exhibited a globule size of 55.32 ± 2.15 nm, PDI value of 0.365 ± 0.06, and zeta potential of -12.32 ± 0.23 mV. The presence of SNPs was confirmed by UV-visible spectroscopy in the range of 290 nm. The SEM image showed that the particles were spherical with a size of 40 nm. The ATR-FTIR study showed no interaction, and all the major peaks were preserved in the formulations. An antimicrobial and antifungal study of SNPs was carried out against Gram-positive bacteria (Staph. aureus, Bacillus), Gram-negative bacteria (E. coli and Bordetella), and fungal strains (Candida albicans). The study showed that Citrus limon extract SNPs exhibited better antimicrobial and antifungal activities against Staph. aureus, Bacillus, E. coli, Bordetella, and Candida albicans at a minimal inhibitory concentration of 50 µg/mL. Different antibiotics were used alone and in combination with SNPs of Citrus limon extract to evaluate their activity against various strains of bacteria and fungal strains. The study showed that using SNPs of Citrus limon extract with antibiotics has a synergistic effect against Staph.aureus, Bacillus, E. coli, Bordetella, and Candida albicans. SNPs were embedded in nanohydrogel formulations for in vivo (wound healing) studies. In preclinical studies, SNPs of Citrus limon extract embedded within a nanohydrogel formulation (NHGF4) have shown promising results. To be widely used in clinical settings, further studies are needed to evaluate their safety and efficacy in human volunteers.

Antidiabetic, Antihyperlipidemic, and Antioxidant Evaluation of Phytosteroids from Notholirion thomsonianum (Royle) Stapf.

Diabetes mellitus (DM) is a metabolic complication and can pose a serious challenge to human health. DM is the main cause of many life-threatening diseases. Researchers of natural products have been continuously engaged in treating vital diseases in an economical and efficient way. In this research, we extensively used phytosteroids from Notholirion thomsonianum (Royle) Stapf for the treatment of DM. The structures of phytosteroids NtSt01 and NtSt02 were confirmed with gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) analyses. Through in vitro studies including α-glucosidase, α-amylase, and DPPH assays, compound NtSt01 was found to be comparatively potent. An elevated dose of compound NtSt01 was also found to be safe in an experimental study on rats. With a dose of 1.0 mg/kg of NtSt01, the effect on blood glucose levels in rats was observed to be 519 ± 3.98, 413 ± 1.87, 325 ± 1.62, 219 ± 2.87, and 116 ± 1.33 mg/dL on the 1st, 7th, 14th, 21st, and 28th, days, respectively. The in vivo results were compared with those of glibenclamide, which reduced the blood glucose level to 107 ± 2.33 mg/dL on the 28th day. On the 28th day of NtSt01 administration, the average weights of the rats and vital organs (liver, kidney, pancreas, and heart) remained healthy, with a slight increase. The biochemical parameters of the blood, i.e., serum creatinine, blood urea, serum bilirubin, SGPT (or ALT), and serum alkaline phosphatase, of rats treated with NtSt01 remained in the normal ranges. Similarly, the serum cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels also remained within the standard ranges. It is obvious from our overall results that the phytosteroids (specifically NtSt01) had an efficient therapeutic effect on the blood glucose level, protection of vital organs, and blood biochemistry.

Optimization of Chitosan-Decorated Solid Lipid Nanoparticles for Improved Flurbiprofen Transdermal Delivery.

Transdermal delivery is a potential alternative route to oral administration for drugs associated with stomach discomfort, such as flurbiprofen, a widely nonsteroidal anti-inflammatory drug (NSAID). This study aimed to design solid lipid nanoparticle (SLN) transdermal formulations of flurbiprofen. Chitosan-coated SLNs were prepared by the solvent emulsification method, and their properties and permeation profiles across the excised rat skin were characterized. The particle size of uncoated SLNs was at 695 ± 4.65 nm, which increased to 714 ± 6.13, 847 ± 5.38, and 900 ± 8.65 nm upon coating with 0.05, 0.10, and 0.20% of chitosan, respectively. The drug association efficiency was improved when a higher concentration of chitosan was employed over SLN droplets that endowed a higher affinity of flurbiprofen with chitosan. The drug release was significantly retarded as compared to the uncoated entities and followed non-Fickian anomalous diffusion that was depicted by "n" values of >0.5 and <1. Also, the total permeation of chitosan-coated SLNs (F7-F9) was significantly higher than that of the noncoated formulation (F5). Overall, this study has successfully designed a suitable carrier system of chitosan-coated SLNs that provide insight into the current conventional therapeutic approaches and suggest new directions for the advancements in transdermal drug delivery systems for improved permeation of flurbiprofen.