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Rifaximin, a semi‐synthetic derivative of rifamycin is a BCS class IV drug having poor physicochemical properties. These poor physicochemical properties pose a major challenge in dosage form production and limited bioavailability restricts the systemic use of rifaximin. This study focuses on the improvement of physicochemical properties and in‐vivo bioavailability of rifaximin by utilizing co‐crystallization approach. Co‐crystallization of rifaximin with l‐proline (amino acid) resulted in improvement of physicochemical properties like saturation solubility, dissolution rate, flow‐ability, and 1.5‐fold improvement in anti‐microbial activity as compared to pure rifaximin. Ex‐vivo permeation rate was improved approximately two‐fold and in an in‐vivo study utilizing Sprague Dawley rats, relative bioavailability was estimated to be 785.5967±55.8986. The data suggest exponential improvement of both, physicochemical properties and bioavailability in the co‐crystallized form of rifaximin. This study might be a first step for the use of rifaximin in systemic infections and may open a path for rifaximin as a drug of choice for various bacterial infections. [ABSTRACT FROM AUTHOR]

Thiocolchicoside (THC) is a drug under the category of BCS III. Due to its high molecular weight, it has poor oral bioavailability and low skin permeability. This study aims to find an alternative delivery method for THC that enhances its bioavailability through nasal application approach. In situ gels containing plain or liposomal THC with different combinations of Pluronic® F127 and PEG 400 were prepared. Liposome formulations were prepared using the thin film hydration method and tested for their characterization such as for drug content, particle size, and zeta potential. In vivo pharmacokinetic parameters of formulations such as Cmax, Tmax, and AUC were tested on the rabbit model. The formulations were also scrutinized for their cell viability properties. Formulation composition with 2% soybean phosphatidylcholine and 10 mg THC exhibited ∼94% entrapment efficiency, minimum particle size 101.32 nm, low polydispersity index 0.225 and +0.355 zeta potential. In situ liposomal dispersion containing 15% Pluronic® F127 turned into gel at nasal temperature. Cell lines were unharmed for 48 h. İn situ liposomal gels showed 1.5x higher blood concentration than the control formula. In situ gels of liposomal THC formulations offer advantages over traditional nasal solutions, demonstrating comparable bioavailability to parenteral medication while also preserving the health of nasal mucosa cells. [ABSTRACT FROM AUTHOR]

Background: The present research investigates the nasal delivery of Lamotrigine by incorporating it into a natural in-situ gelling system. Additionally, the retention of the drug in the nasal cavity was enhanced by employing the natural mucoadhesive polymer locust bean gum (LBG). A preliminary investigation was conducted to determine the optimal concentration of gellan gum. The dosage of the drug was calculated using the Robinson Erikson equation. The central composite design was utilized to optimize the influence of individual variables such as gellan gum and locust bean gum on various responses, including gelation time, gel viscosity, mucoadhesive strength, and the time taken for the drug to release half of its initial concentration (t50). The goal of the current study was to evaluate the in-vivo effectiveness of intra nasal in-situ gel of Lamotrigine. Methodology: The pharmacokinetic and tissue distribution studies were carried out to evaluate the brain targeting efficiency of lamotrigine. Blood samples and tissues of various vital organs like brain, liver, kidneys and heart were obtained at different time intervals, plasma and tissue concentration of Lamotrigine was estimated by reverse phase HPLC. Results: According to the pharmacokinetic analysis, Cmax and AUC0-α is found to be significantly more (P<0.05) for nasal route compared to oral route. In comparison to the oral route, Cmax and AUC0-α was 7 and 6.5 folds more for IN route. The absolute bioavailability was found to be 159.07%. with regard to the oral group, minimal drug was present in any of the other tissue samples. In the pharmacodynamic data also the formulation through nasal route showed a significant difference compared to oral route (pure drug suspension) delivery in PTZ induced study. [ABSTRACT FROM AUTHOR]

Novel physically-crosslinked PVA membranes blended with Aloe vera extract were fabricated by solution-casting method. Physically-crosslinking process is depending on the rearrangement of PVA chains forming intermolecular hydrogen bonding with removal of water molecules using propanol as a stabilizing agent. The structure of crosslinked membranes was characterized by FT-IR, SEM, TGA, and XRD analyses and confirmed via gel faction and swelling ratio studies. Caffeine and vitamin C loaded-PVA/Aloe vera membranes were bio-assessed in terms of their impact on the wound healing using Wistar albino rats as an animal model. In vitro evaluation includes protein adsorption showed that the fabricated membranes improved significantly the wound healing ability via enhancing the tissue platelet aggregation. In addition, resulting adequate in vitro release behavior for the loaded ingredients in the potential application. In-vivo results displayed that rats full-thickness wounds were remarkably reduced after PVA/Aloe vera/Vitamin C membranes treatment, as shown by a reduction in the area of the wounds when compared to wounds treated with cotton gauze and PVA/Aloe vera membranes. Furthermore, the treated wounds with PVA/Aloevera/caffeine show more wound closer comparing to that incorporate vitamin C and the PVA/Aloevera incorporated both caffeine and vitamin C give the most significant healing that show reappearance of hair covered the wound area. Histological examinations of wounds covered in membranes showed a successful re-epithelialization, demonstrating caffeine's and vitamin C's efficacy. These results demonstrated that, PVA/Aloe Vera/Caffeine and PVA/Aloe vera/vitamin C membrane have remarkable wound healing and skin regeneration properties. [ABSTRACT FROM AUTHOR]

Introduction: Although various products are commonly used for skin rejuvenation, solid-type hyaluronic acid (HA) as an injectable form has not been researched or utilized. This study aimed to demonstrate the safety and efficacy of solid-type HA in thread form, which differs from the conventional gel-type HA commonly used. Method: Solid-type HA threads, conventional HA fillers, and polydioxanone (PDO) threads were inserted into the dorsal subcutaneous layer of mice. Photographs were taken on days 0, 1, 3, and 7, and on day 7, the samples were harvested for histological analysis. Inflammatory reactions and detection of collagen were confirmed through tissue staining, and real-time PCR was conducted to quantify collagen synthesis. Results: In the histological analysis, the PDO threads exhibited a greater inflammatory response compared to the HA threads. Masson's trichrome staining revealed a higher degree of collagen synthesis in the HA thread group compared to the HA filler group. While collagen type 1 expression was significantly higher in the PDO thread group than in the HA thread group, the HA thread group showed higher expression levels of collagen type 3. Furthermore, the PDO thread group demonstrated a statistically significant increase in TGF-β1 compared to the HA group. Conclusion: This in vivo study demonstrated the stable application of solid-type pure HA threads and their potential for inducing collagen production, while also yielding a low inflammatory response. The findings highlight the promising applications of solid-type HA in the field of cosmetic dermatology. No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Background: Herbal cosmetics, particularly herbal hair oils, have gained popularity due to their perceived efficacy and minimal adverse effects. This study aimed to formulate and evaluate herbal hair oils for promoting hair growth. Methodology: Various herbal extracts, including Coconut, Curry leaves, Amla, Fenugreek, and Onion, were prepared and incorporated into virgin Coconut oil. Phytochemical screening, total flavonoid content, organoleptic evaluation, chemical analysis (acid value, saponification value, specific gravity), stability studies, antioxidant assay (DPPH), antimicrobial assay, sensitivity studies, and in-vivo hair growth activity were conducted. Results: Organoleptic evaluation revealed characteristic odors and colors across formulations. Chemical analysis showed acceptable values for acid value (0.68 - 1.86 mg KOH/g), saponification value (117.87 - 224.27 mg KOH/g), and specific gravity (0.865 - 0.933 g/cm^3). Stability studies over 45 days demonstrated consistent physicochemical properties. The DPPH assay indicated dose-dependent antioxidant activity, with inhibition ranging from 13.8% to 66.5%. Antimicrobial assay showed inhibition zones ranging from 6 mm to 20 mm against Staphylococcus aureus. Sensitivity studies exhibited no adverse reactions. In-vivo hair growth activity demonstrated significant improvements compared to controls. Discussion: The formulated herbal hair oils exhibited promising physicochemical properties, antioxidant activity, antimicrobial efficacy, safety, and hair growth promotion in animal models. These findings suggest their potential as natural remedies for hair care. Conclusion: Herbal hair oils formulated in this study show significant potential for promoting hair growth and addressing hair-related concerns. Whereas, formulation F3 shown significant efficacy across multiple parameters among the formulations. Further research and clinical trials are warranted to validate their efficacy and safety for human use.

Abstract Background Chronic kidney disease (CKD) is a worldwide public health problem affecting millions of people. Probiotics and postbiotics are associated with valuable compounds with antibacterial, anti-inflammatory, and immunomodulatory effects, preserving renal function in CKD patients. The current study is aimed to evaluate the efficacy of Limosilactobacillus fermentum (L. fermentum) and its postbiotic in an animal model of cisplatin-induced CKD. Methods The animals were divided into four experimental groups (normal mice, CKD mice with no treatment, CKD mice with probiotic treatment, and CKD mice with postbiotic treatment). CKD mice were induced by a single dose of cisplatin 10 mg/kg, intraperitoneally. For 28 days, the cultured probiotic bacteria and its supernatant (postbiotic) were delivered freshly to the related groups through their daily water. Then, blood urea nitrogen (BUN) and creatinine (Cr) of plasma samples as well as glutathione (GSH), lipid peroxidation, reactive oxygen species, and total antioxidant capacity of kidneys were assessed in the experimental mice groups. In addition, histopathological studies were performed on the kidneys. Results Application of L. fermentum probiotic, and especially postbiotics, significantly decreased BUN and Cr (P

Red dragon fruit (Hylocereus polyrhizus) is a tropical fruit that is currently cultivated in all tropical parts of the world. It is popular to consume its fruit flesh, while the peel is often thrown away. This red dragon fruit peel (RDFPE) is known to possess lots of phytochemical compounds with multitudes of usage, amongst them as an analgesic and antipyretic. Therefore, the active compounds of RDFPE play an important role in the natural product. This study aims to observe and analyze the analgetic and antipyretic activity possessed by red dragon fruit peel. This study is an in-vivo experiment on 25 white male rats divided into five groups, in which each group receive Na CMC, acetaminophen, and the other three groups will receive three different doses of RDFPE (500 mg/kg, 750 mg/kg, and 1000 mg/kg), respectively. Acetic acid writhing and tail immersion methods were performed to induce inflammation and Brewer’s yeast injection performed induced pyrexia. In the investigation of the acetic acid writhing test, the intervention was administered before induction, and for the tail immersion test, induction was given before and after the intervention was administered. Meanwhile, in brewer’s yeast-induced pyrexia, the rectal temperature was measured before induction, 24 hours after induction, and each hour for five four after the intervention; intervention was administered 24 hours after induction. This study found that RDFPE at the dose of 750 mg/kg and 1000 mg/kg are effective as an analgesic by reducing the average writhing and delaying the tail retraction of the experiment subject and also effective as an antipyretic by reducing the elevated temperature of the experiment subject (p

Employment of mesoporous silica nanostructures (MSNs) in the drug delivery field has shown a significant potential for improving the oral delivery of active pharmaceutical products with low solubility in water. Mirtazapine (MRT) is a tetracyclic antidepressant with poor water solubility (BCS Class II), which was recently approved as a potent drug used to treat severe depression. The principle of this research is to optimize the incorporation of Mirtazapine into MSNs to improve its aqueous solubility, loading efficiency, release performance, and subsequent bioavailability. The formulation was optimized by using of Box-Behnken Design, which allows simultaneous estimation of the impact of different types of silica (SBA-15, MCM-41, and Aluminate-MCM-41), a different drug to silica ratios (33.33%, 49.99%, and 66.66%), and different drug loading procedures (Incipient wetness, solvent evaporation, and solvent impregnation) on the MRT loading efficiency, aqueous solubility and dissolution rate. The optimized formula was achieved by loading MRT into SBA-15 at 33.33% drug ratio prepared by the incipient wetness method, which displayed a loading efficiency of 104.05%, water solubility of 0.2 mg/ml, and 100% dissolution rate after 30 min. The pharmacokinetic profile of the optimized formula was obtained by conducting the in-vivo study in rabbits which showed a marked improvement (2.14-fold) in oral bioavailability greater than plain MRT. The physicochemical parameters and morphology of the optimized formula were characterized by; gas adsorption manometry, scanning electron microscopy (SEM), polarized light microscopy (PLM), Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD).

The technologies for fabrication of nanocrystals have an immense potential to improve solubility of a variety of the poor water-soluble drugs with subsequent enhanced bioavailability. Repaglinide (Rp) is an antihyperglycemic drug having low bioavailability due to its extensive first-pass metabolism. Microfluidics is a cutting-edge technique that provides a new approach for producing nanoparticles (NPs) with controlled properties for a variety of applications. The current study's goal was to engineer repaglinide smart nanoparticles (Rp-Nc) utilizing microfluidic technology (Dolomite Y shape), and then to perform in-vitro, in-vivo, and toxicity evaluations of them. This method effectively generated nanocrystals with average particle sizes of 71.31 ± 11 nm and a polydispersity index (PDI) of 0.072 ± 12. The fabricated Rp's crystallinity was verified by Differential scanning calorimetry (DSC) and Powder X-ray diffraction (PXRD). In comparison to the raw and commercially available tablets, the fabricated Rp's nanoparticles resulted in a higher saturation solubility and dissolving rate (p < 0.05). Rp nanocrystals had a considerably lower (p < 0.05) IC50 value than that of the raw drug and commercial tablets. Moreover, Rp nanocrystals at the 0.5 and 1 mg/kg demonstrated a significant decrease in blood glucose level (mg/dL, p < 0.001, n = 8) compared to its counterparts. Rp nanocrystals at the 0.5 mg/kg demonstrated a significant decrease (p < 0.001, n = 8) in blood glucose compared to its counterparts at a dose of 1 mg/kg. The selected animal model's histological analyses and the effect of Rp nanocrystals on several internal organs were determined to be equivalent to those of the control animal group. The findings of the present study indicated that nanocrystals of Rp with improved anti-diabetic properties and safety profiles can be successfully produced using controlled microfluidic technology, an innovative drug delivery system (DDS) approach. [ABSTRACT FROM AUTHOR]

Employment of mesoporous silica nanostructures (MSNs) in the drug delivery field has shown a significant potential for improving the oral delivery of active pharmaceutical products with low solubility in water. Mirtazapine (MRT) is a tetracyclic antidepressant with poor water solubility (BCS Class II), which was recently approved as a potent drug used to treat severe depression. The principle of this research is to optimize the incorporation of Mirtazapine into MSNs to improve its aqueous solubility, loading efficiency, release performance, and subsequent bioavailability. The formulation was optimized by using of Box-Behnken Design, which allows simultaneous estimation of the impact of different types of silica (SBA-15, MCM-41, and Aluminate-MCM-41), a different drug to silica ratios (33.33%, 49.99%, and 66.66%), and different drug loading procedures (Incipient wetness, solvent evaporation, and solvent impregnation) on the MRT loading efficiency, aqueous solubility and dissolution rate. The optimized formula was achieved by loading MRT into SBA-15 at 33.33% drug ratio prepared by the incipient wetness method, which displayed a loading efficiency of 104.05%, water solubility of 0.2mg/ml, and 100% dissolution rate after 30 min. The pharmacokinetic profile of the optimized formula was obtained by conducting the in-vivo study in rabbits which showed a marked improvement (2.14-fold) in oral bioavailability greater than plain MRT. The physicochemical parameters and morphology of the optimized formula were characterized by; gas adsorption manometry, scanning electron microscopy (SEM), polarized light microscopy (PLM), Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD). [ABSTRACT FROM AUTHOR]

With the application of the quality by design (QbD) approach, a high-pressure homogenizer (HPH) methodology was employed to develop methotrexate nanosuspension (MTX-NS) to boost bioavailability. The Ishikawa diagram was used to analyze potential risk factors in formulation development. To screen and study the impact of various formulation and process factors on the critical quality attributes (CQA), the Placket–Burman design and central composite design were utilized. The number of HPH cycles, poloxamer 188 concentration, and tween 80 concentration were shown to be significant parameters (P

The most frequent type of primary liver cancer is hepatocellular carcinoma (HCC), accounting for approximately 90% of primary liver cancers and a third leading cause of cancer deaths. In the current study, the synthesized compound 3 was re-formulated using tetraethyl orthosilicate (TEOS) with weight ratio (1:1) via sol-gel technique. The prepared material has been examined using Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray elemental analysis (EDX), and scanning and transmission electron microscopes (SEM and TEM). Herein, we investigate the mode of action of 3 as potent anti-liver cancer in vivo as normal and nano-forms. Rats were given a single dosage of 50 mg/kg b.wt. of HCC through an intraperitoneal injection (ip). A single dosage of CCl4 (2 ml/kg IP) was also given to rats 2 weeks later. Several liver, tumor and oxidative stress biomarkers were detected including liver enzymes; alanine and aspartate aminotransferases (ALT and AST), alkaline phosphatse (ALP), gamma glutamyl transferase (GGT), glutathione (GSH), lipid peroxide (MDA), catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), α-fetoprotein and α-L-Fucosidase. Hepatic pathological pictures were also performed for the documentation of the presence of HCC and supported the biochemical results. Moreover, the DNA damage in liver tissues of male rats using comet assay was studied. The results showed that the HePG2 (− ve) group of rats exhibited a significant reduction (P < 0.05) in DNA damage values (9.30 ± 0.89) relative to other treatment groups. Nevertheless, the DNA damage values in the HePG2 (+ ve) and 5-flurouracil groups were significantly higher (P < 0.01) compared to the HePG2 (− ve) group. Additionally, HePG2 (coated 3) and HePG2 (3) groups exhibited significant decrease in the DNA damage compared to those in HePG2 (+ ve) group. [ABSTRACT FROM AUTHOR]

Electrospinning technology has been introduced as a new drug delivery system particularly when used for topical administration which shows excellent results in the treatment of various skin diseases. The combination of synthetic polymer (Polyvinyl alcohol) with biocompatible and biodegradable polymer (Chitosan) in a specific ratio to carry antibacterial agent (Fusidic acid) in the form of electrospun nanofibers to be used in wound dressing to treat different types of infections and ulcerations of the skin. The prepared electrospun nanofibers solution is tested for viscosity to assist in selection of suitable ratio of (PVA/CS) to load the antibacterial agent and produce nanofibers loaded fusidic acid. The evaluation of nanofibers is performed by studying the morphology of nanofibers, loading efficiency, swelling test, ex-vivo which carried by using Franz diffusion cell and in-vivo drug release profile by testing the nanofibers on rat to determine the percent of wound contraction and compare the average cumulative drug release with conventional dosage form to understand the bust mechanism from the surface of nanofibers and controlled drug release from the formula. [ABSTRACT FROM AUTHOR]

Context: One of the major limitations of conventional radiological procedures is the presence of considerable overlapping and lack of clear, three-dimensional information. Cone-beam computed tomography (CBCT) has emerged as an effective imaging modality in such situations offering high-quality images and lower radiation exposure to patients. Aim: The aim of the present study was to assess the role of CBCT in the detection of intra-bony defects in patients with advanced periodontal disease. Settings and Design: The present study was designed as a prospective, observational study wherein patients aged between 35–55 years with advanced periodontal disease who were indicated for periodontal treatment in form of periodontal surgeries were selected from the outpatient department (OPD) based on defined inclusion and exclusion criteria. Materials and Methods: Sixty patients with chronic periodontitis with 12 teeth each including 6 anterior and 6 posterior teeth were selected for making measurements pre- and peri-operatively while bone defects were measured first with the help of CBCT software installed in an individualized system devised to be used for storing and analyzing CBCT images and then, during surgical intervention using standardized UNC-15 periodontal probe and compared. Statistical Analysis Used: Statistical analysis was performed using SPSS version 18.0 (SPSS Inc., Chicago, IL, USA). The measurements obtained with the help of CBCT software installed in the personalized system and those obtained on surgical exploration were compared in each anterior and posterior tooth with the help of paired-sample t-test while Pearson's correlation(r) was used to test the correlation between the observed values. The level of statistical significance was set at P < 0.05. Results: The results were found to be highly significant both in terms of statistical (P-value) and clinical (r) significance for various sites in the anterior and posterior teeth in all instances. Conclusions: From the observations made from the present study, it could be concluded that CBCT provided highly precise assessment of bone topography equivalent to the judgment obtained during surgical exposure at the sites of interest preoperatively, which helped in assessing the exact type and depth of defect present and helped in optimizing surgical treatment planning. [ABSTRACT FROM AUTHOR]

The technologies for fabrication of nanocrystals have an immense potential to improve solubility of a variety of the poor water-soluble drugs with subsequent enhanced bioavailability. Repaglinide (Rp) is an antihyperglycemic drug having low bioavailability due to its extensive first-pass metabolism. Microfluidics is a cutting-edge technique that provides a new approach for producing nanoparticles (NPs) with controlled properties for a variety of applications. The current study’s goal was to engineer repaglinide smart nanoparticles (Rp-Nc) utilizing microfluidic technology (Dolomite Y shape), and then to perform in-vitro, in-vivo, and toxicity evaluations of them. This method effectively generated nanocrystals with average particle sizes of 71.31 ± 11 nm and a polydispersity index (PDI) of 0.072 ± 12. The fabricated Rp’s crystallinity was verified by Differential scanning calorimetry (DSC) and Powder X-ray diffraction (PXRD). In comparison to the raw and commercially available tablets, the fabricated Rp’s nanoparticles resulted in a higher saturation solubility and dissolving rate (p < 0.05). Rp nanocrystals had a considerably lower (p < 0.05) IC50 value than that of the raw drug and commercial tablets. Moreover, Rp nanocrystals at the 0.5 and 1 mg/kg demonstrated a significant decrease in blood glucose level (mg/dL, p < 0.001, n = 8) compared to its counterparts. Rp nanocrystals at the 0.5 mg/kg demonstrated a significant decrease (p < 0.001, n = 8) in blood glucose compared to its counterparts at a dose of 1 mg/kg. The selected animal model’s histological analyses and the effect of Rp nanocrystals on several internal organs were determined to be equivalent to those of the control animal group. The findings of the present study indicated that nanocrystals of Rp with improved anti-diabetic properties and safety profiles can be successfully produced using controlled microfluidic technology, an innovative drug delivery system (DDS) approach.

Abstract The objective of the present study was to develop time delayed chronotherapeutic formulation of Eplerenone (Ep) to provide rapid drug release after a pre-determined lag time for the treatment of early morning hypertension. Cyclodextrin complexation was used to prepare fast release Ep core tablets. The developed core tablets were then coated with different rate-controlling polymers using compression coating technique. The developed tablets were evaluated for hardness, friability, drug content and swelling index. The in-vitro drug release was carried out to study the effect of different coating materials on drug release and lag time. Tablets selected for stability study were those showing lag time of 5-7 hours followed by complete drug release; F2, F3, F7, F8, and F12. The in-vivo study was carried out on tablets with the highest t90 as compared to commercial tablets after being administered to healthy human volunteers where plasma Ep and urinary Na/K ratio were determined. Results suggested that this approach was able to provide delayed release Ep formulations that will be useful for patients with morning surge in blood pressure.

Objectives: Artemether (ART), an antimalarial drug, have poor solubility and low bioavailability. Therefore, solid dispersion of the drug was formulated using Soluplus (SOL) and was incorporated in the fast disintegrating tablet. Materials and Methods: The solid dispersion (SD) was prepared using the solvent evaporation method using a rotary evaporator. The optimized SD was evaluated and then incorporated into the tablet. Results: Solubility studies revealed that ART SD A3 of ratio 1:3 (ART: SOP) showed a significantly higher solubility and dissolution rate than plain ART. FTIR results indicated that there was no incompatibility between the drug and hydrophilic carrier. The DSC as well as XRD studies indicated the transformation from crystalline state of drug into the amorphous form. SEM studies revealed the deposition of ART on the surface of the hydrophilic carrier. In-vitro antimalarial activity was improved of the ART due to the SD formulation. Fast disintegrating tablet of ART SD A3 was produced by using directly compressible excipients such as Ludiflash and Ludipress. Ludiflash containing tablet showed fast disintegration with higher drug release. The pharmacokinetic study in mice showed increased Cmax and AUC0-24 by 1.88- and 3.19-fold as compared to those of plain drug. Conclusion: The prepared SDs using SOP provided a platform for increased solubility and also improved the bioavailability of ART with feasibility for tablet formulation. [ABSTRACT FROM AUTHOR]

Abstract The purpose of this in‐vivo study was to evaluate the clinical performance of restorations placed in non‐carious cervical lesions (NCCLs), using different cavity preparation designs, after 7.7 years. A total of 85 NCCLs with coronal margins in enamel and cervical margins in dentin were randomly assigned to the following treatment protocols: dentin surface cleaning, dentin surface roughening with round bur plus flowable composite, dentin surface roughening/cervical groove preparation with round bur, dentin surface roughening/cervical groove preparation with round bur plus flowable composite. After enamel beveling and selective enamel etching, the defects were restored with composite. The restorations were assessed by two independent, calibrated and blinded investigators, using modified USPHS criteria. At 7 years (7.7 (± 0.35)), a total of 64 restorations (75.3%) were available for follow‐up examination. The total retention rate, irrespective of the test groups, was 82.8%. Restorations placed without any preparation showed the highest loss rate (27.8%). Esthetic appearance, marginal adaptation, anatomic form and marginal discoloration did not differ significantly between the groups. Composites are long‐term stable materials for restoring NCCLs. Restorations placed without any dentin preparation (cavity cleaning only) showed the highest loss rate.

With the application of the quality by design (QbD) approach, a high-pressure homogenizer (HPH) methodology was employed to develop methotrexate nanosuspension (MTX-NS) to boost bioavailability. The Ishikawa diagram was used to analyze potential risk factors in formulation development. To screen and study the impact of various formulation and process factors on the critical quality attributes (CQA), the Placket-Burman design and central composite design were utilized. The number of HPH cycles, poloxamer 188 concentration, and tween 80 concentration were shown to be significant parameters (P<0.05), that were further optimized using Central Composite Design. The zeta potential of optimized lyophilized MTX-NS was determined to be -11.6 ± 7.52 mV and the average particle size was 260 ± 0.25 nm. In vitro cytotoxicity experiments revealed a greater than 80% inhibition, with apoptotic cells shrinking, fragmentation, and cell death. Furthermore, the Cmax and AUC0-t were increased by 2.53 and 8.83 folds, respectively. The relative bio- availability of MTX-NS was found to be 8.83 times higher than that of MTX-aqueous dispersion. As a result, the QbD method resulted in the development of a lyophilized MTX-NS with process understanding and control based on quality risk management. [ABSTRACT FROM AUTHOR]

The purpose of this in‐vivo study was to evaluate the clinical performance of restorations placed in non‐carious cervical lesions (NCCLs), using different cavity preparation designs, after 7.7 years. A total of 85 NCCLs with coronal margins in enamel and cervical margins in dentin were randomly assigned to the following treatment protocols: dentin surface cleaning, dentin surface roughening with round bur plus flowable composite, dentin surface roughening/cervical groove preparation with round bur, dentin surface roughening/cervical groove preparation with round bur plus flowable composite. After enamel beveling and selective enamel etching, the defects were restored with composite. The restorations were assessed by two independent, calibrated and blinded investigators, using modified USPHS criteria. At 7 years (7.7 (± 0.35)), a total of 64 restorations (75.3%) were available for follow‐up examination. The total retention rate, irrespective of the test groups, was 82.8%. Restorations placed without any preparation showed the highest loss rate (27.8%). Esthetic appearance, marginal adaptation, anatomic form and marginal discoloration did not differ significantly between the groups. Composites are long‐term stable materials for restoring NCCLs. Restorations placed without any dentin preparation (cavity cleaning only) showed the highest loss rate. [ABSTRACT FROM AUTHOR]

This study carried out to improve bioavailability and reduce dose frequency of Bosentan, because of drug accumulation due to conventional therapy it cause serious liver toxicity. Bosentan loaded nanostructured lipid carriers (NLCs) prepared by using high-speed homogenization followed by an ultra-sonication. Optimization done by response surface methodology to identify the effect of solid to liquid lipid ratio (X1) and surfactant strength (X2) on the particle size (Y1) and drug loading (Y2). From the Preformulation study Precirol ATO 5, Transcutol HP and Poloxamer 188 selected as a solid lipid, liquid lipid and surfactant, respectively. Optimize formula having solid to liquid lipid ratio (85:15) %w/w and surfactant strength 1% w/v. Final formulation contained particle size 144.5±0.34 nm (n=3), surface charge -36.6 mv and 90.89±0.10 % (n=3) drug entrapment. Characterization performed using DSC, FTIR and TEM analysis. The Haemolytic study carried out to check blood compatibility. In-Vitro and Ex -Vivo drug release study shows 93.36% and 88.87 %, respectively after 24 hours. In-vivo Performance was conducted on wistar Albino rats. As per the result of in-vivo study pharmacokinetic parameters were quite different for Conventional formulation and NLCs. Bosentan NLCs absorb through the lymphatic system containing Peyer's patches. Optimize stable formulation gives the controlled release according to Fick's law. As uptake of Bosentan NLCs through Peyer's patches it may improve the bioavailability of the drug and reduce the liver toxicity. [ABSTRACT FROM AUTHOR]

Glutamic acid-co-poly(acrylic acid) (GAcPAAc) hydrogels were prepared by the free radical polymerization technique using glutamic acid (GA) as a polymer, acrylic acid (AAc) as a monomer, ethylene glycol dimethylacrylate (EGDMA) as a cross-linker, and ammonium persulfate (APS) as an initiator. Increase in gel fraction was observed with the increasing concentration of glutamic acid, acrylic acid, and ethylene glycol dimethylacrylate. High percent porosity was indicated by developed hydrogels with the increase in the concentration of glutamic acid and acrylic acid, while a decrease was seen with the increasing concentration of EGDMA, respectively. Maximum swelling and drug release was exhibited at high pH 7.4 compared to low pH 1.2 by the newly synthesized hydrogels. Similarly, both swelling and drug release increased with the increasing concentration of glutamic acid and acrylic acid and decreased with the increase in ethylene glycol dimethylacrylate concentration. The drug release was considered as non-Fickian transport and partially controlled by viscoelastic relaxation of hydrogel. In-vivo study revealed that the AUC0–∞ of fabricated hydrogels significantly increased compared to the drug solution and commercial product Keten. Hence, the results indicated that the developed hydrogels could be used as a suitable carrier for controlled drug delivery.

Optimized formulations were subjected to various in vivo studies like anti-inflammatory activity, Nickel induced dermatitis, irritation study and Acute and repeated dose dermal toxicity studies. Clobetasol propionate (CP) has anti-inflammatory, immunomodulatory, and antiproliferative activity. The aim of the present work was to test the hypothesis that the addition CP in nanoemulsions would result in enhancement CP delivery and leading to better antipsoriatic activity. Nanoemulsions were prepared by aqueous phase titration method, using Tea Tree oil, Tween 20, Transcutol P, and distilled water as the oil phase, surfactant, co-surfactant and aqueous phase, respectively.We developed a topical O/W nanoemulsion in which drug is incorporated in disperse phase of oil and evaluated its efficacy against different types of in vivostudies. It was also found that the significantly increased their anti-inflammatory activity. It was reported that CP-loaded nanoemulsion significantly increased NTPDase (Nucleoside triphosphate diphosphohydrolases) activity in lymphocytes. This membrane protein is responsible for the hydrolysis of extracellular ATP (Adenosine triphosphate) which is responsible for cell proliferation, differentiation and inflammatory processes. In vivoirritation studies did not show any irritation in spite of having high amount of surfactant. Group treated with CP loaded nanoemulsion gel showed no evident toxicity even on repeated exposure. On the basis of above in vivo study we conclude that developed nanoemulsion is safe for human. [ABSTRACT FROM AUTHOR]

Among emerging layered materials, 2D transition metal dichalcogenides (TMDs) nanosheets (n-sheets) have received increasing attention for optoelectronics, energy storage, and, recently, for bioremediation and advanced biomedical applications; however, a lack of ecotoxicological in vivo studies is evident. Herein, for the first time, the potential nanotoxicity of liquid phase exfoliated Group VI TMDs n-sheets (MoS 2 , WS 2 , WSe 2 , and MoSe 2) was comparatively investigated using zebrafish embryos (Z-EBs) as an in-vivo model. The 2D n-sheets were produced directly in aqueous-medium, the obtained n-sheets were characterized by scanning electron microscopy, Raman and visible spectroscopy, and their potential nanotoxicity was investigated by fish embryo test OECD TG 236. Chorionated and dechorionated embryos were used to assess the severity of TMD exposure. The survival rate, sublethal alteration during embryogenesis, hatching rate, and mortality were evaluated. TMDs n-sheets tend to adhere to the Z-EBs surface depending on their chemistry. Despite this, TMDs did not show lethal effects; weak sublethal effects were found for MoS 2 and WSe 2 , while slight hatching delays were registered for MoSe 2 and WSe 2. The observed effects are attributable to the TMDs' tendency to interact with Z-EBs, because of the different chemistry. This work demonstrates how water-dispersed TMDs are potential eco/biocompatible materials. [Display omitted] • Group VI Transition Metal Dichalcogenides were tested toward zebrafish embryos model. • MoS 2 , WS 2 , WSe 2 , MoSe 2 nanosheets were prepared in water via liquid phase exfoliation. • TMDs ecotoxicity was tested on chorionated and dechorionated zebrafish embryos. • Some TMDs induced slight sublethal alterations and hatching delays. • TMDs not induced lethal effects along zebrafish embryogenesis. [ABSTRACT FROM AUTHOR]

In this study, atmospheric pressure chemical ionisation-mass spectrometry (APCI-MS) was successfully applied to understand the effect of phenolic compounds on the release of olive oil aroma compounds. Eight aroma compounds were monitored under in-vivo and in-vitro dynamic conditions in olive oil with and without the addition of virgin olive oil (VOO) biophenols. Three model olive oils (MOOs) were set up with identical volatile compounds concentrations using a refined olive oil (ROO). Phenolics were extracted from VOOs and were added to two MOOs in order to obtain two different concentrations of phenolic compounds (P+ = 354 mg kg −1 ; P++ = 593 mg kg −1 ). Another MOO was without VOO biophenols (P−). Phenolic compounds impacted both the intensity and time of aroma release. In the in-vivo study, 1-penten-3-one, trans -2-hexenal and esters had lower release in the presence of higher levels of biophenols after swallowing. In contrast, linalool and 1-hexanol had a greater release. The more hydrophobic compounds had a longer persistence in the breath than the hydrophilic compounds. VOO phenolics-proline-rich proteins complexes could explain the binding of aroma compounds and consequently their decrease during analysis and during organoleptic assessment of olive oil. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the impact of different hydrophobic ion pairs (HIP) on the oral bioavailability of the model drug octreotide in pigs. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate and docusate differing in lipophilicity. These hydrophobic ion pairs were incorporated in self-emulsifying drug delivery systems (SEDDS) based on BrijO10, octyldodecanol, propylene glycol and ethanol in a concentration of 5 mg/ml. SEDDS were characterized regarding size distribution, zeta potential, stability towards lipase, log D SEDDS/release medium and mucus diffusion behavior. The oral bioavailability of octreotide was evaluated in pigs via LC-MS/MS analyses. Most efficient ion pairing was achieved at a molar ratio of 1:3 (peptide: surfactant). SEDDS containing the octreotide-deoxycholate, -decanoate and -docusate ion pair exhibited a mean droplet size of 152 nm, 112 nm and 191 nm and a zeta potential of − 3.7, − 4.6 and − 5.7 mV, respectively. They were completely stable towards degradation by lipase and showed a log D SEDDS/release medium of 1.7, 1.8 and 2.7, respectively. The diffusion coefficient of these SEDDS was in the range of 0.03, 0.11 and 0.17 × 10 − 9 cm 2 /s, respectively. In vivo studies with these HIPs showed no improvement in the oral bioavailability in case of octreotide-decanoate. In contrast, octreotide-deoxycholate and octreotide-docusate SEDDS resulted in a 17.9-fold and 4.2-fold higher bioavailability vs. control. According to these results, hydrophobic ion pairing could be identified as a key parameter for SEDDS to achieve high oral bioavailability. [ABSTRACT FROM AUTHOR]

PLGA (50:50) nanoparticles were prepared to sustain the release of Ethionamide in order to decrease the dose and dosing frequency. It further modified in the form of dry powder inhaler to make suitable for pulmonary administration and increase drug residency in lungs. Ethionamide loaded PLGA nanoparticles were prepared by solvent evaporation method. Freeze dried nanoparticles and anhydrous inhalable grade lactose were mixed manually using geometrical dilution process to modify the nanoparticles in the form of dry powder inhaler. Animal study was conducted to correlate between in-vivo and in-vitro . PLGA nanoparticles showed initial burst release followed by zero order release up to 95.17 ± 3.59% in 24 h. Aerodynamic particle size of optimized dry powder inhaler was found as 1.79 μm. There was no significant aggregation of dry powder inhaler during 6 months of stability study. Area under the concentration-time curve from 0 h to infinity (AUC 0 −∞ ) signifies the prolong residency of ETH in body compartment, revealed from animal study. PLGA 50:50 coated nanoparticles released Ethionamide for the period of 24 h in simulated lungs fluid. Correlation between in-vitro dissolution and in-vivo study was established after performing animal study. Prepared dry powder inhaler maintained Ethionamide concentration above minimum inhibitory concentration for more than 12 h after single dose administration. [ABSTRACT FROM AUTHOR]

Context: Tramadol is a centrally acting analgesic and requires frequent dosing. Hence, judicious selection of retarding formulations is necessary. Transdermal ethosomal gel delivery has been recognized as an alternative route to oral delivery. Objective: The objective was to develop statistically optimized ethosomal systems for enhanced transdermal activity of tramadol vis-à-vis traditional liposomes. Materials and methods: Box-Behnken design was employed for optimization of nanoethosomes using phospholipon 90G (A), ethanol (B), and sonication time (C) as independent variables while dependent variables were the vesicle size (Y1), entrapment efficiency (Y2), and flux (Y3). It was prepared by rotary evaporation method and characterized for various parameters including entrapment efficiency, size and transflux. Preclinical assessments were conducted on Wistar rats to measure the performance of developed formulations. Results: The optimized formulation provided mean vesicles size, reasonable entrapment efficiency and enhanced flux when compared with liposome (control).In-vivoabsorption study showed a significant increase in bioavailability (7.51 times) compared with oral tramadol. The average primary irritancy index was found to be 1.4, indicating it to be non-irritant and safe for use. Discussion and conclusion: The results also demonstrated that encapsulated tramadol increases its biological activity due to the superior skin penetration potential. The preclinical study indicates a significant (P < 0.05) extended analgesic effect compared to oral solution using the hot plate test method. The overall results suggest that developed formulation is an efficient carrier for transdermal delivery of tramadol. [ABSTRACT FROM AUTHOR]

[Display omitted] The intention of this work is to assess the repurposed antimicrobial impact of Levocetirizine dihydrochloride (LVC), which is a well-known antihistaminic drug, in addition, to augment the antimicrobial effect by using terpene-enriched vesicles (TPs). To investigate how various parameters affect TPs aspects, TPs were made employing the ethanol-injection-method and optimized d-optimal design. The TPs were characterized based on their entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum TP was submitted to more examinations. The optimum TP (TP12) showed a spherical vesicle having an EE% of 66.39 ± 0.12%, PS of 243.3 ± 4.60 nm, PDI of 0.458 ± 0.003, and ZP of 24.2 ± 0.55 mV. The in-vitro release study results demonstrated that LVC is sustainedly liberated from the optimum TP compared to LVC-solution. The ex-vivo assessment showed that LVC was released in a more sustained manner from TPs-gel related to LVC solution, optimum TP, and LVC gel. Ex-vivo visualization by confocal laser scanning microscopy showed good deposition of the fluorescein-labeled TP. Further, the in-vitro anti-bacterial effect and biofilm inhibition and detachment assessment confirmed the potency of LVC against Methicillin-resistant-Staphylococcus-aureus (MRSA). The in-silico study demonstrated that the LVC has excellent stability with other ingredients combined with it in the TPs, further, it proved that LVC is a potential candidate for treating MRSA. In-vivo assessments revealed a good antimicrobial effect toward MRSA infection. Moreover, the histopathological evaluation confirmed the safety of using TPs-gel topically. In conclusion, MRSA -related skin infections may be treated using the LVC loaded TPs-gel as a promising system. [ABSTRACT FROM AUTHOR]

Chestnut (Castanea sativa) shells (CSS) are a source of bioactive compounds with well demonstrated in-vitro antioxidant properties. Nevertheless, no in-vivo studies have already evaluated this effect. This study evaluated the effects of the oral daily administration of an eco-friendly CSS extract (50 and 100 mg/kg per body weight (b.w.)) to rats regarding in-vivo antioxidant activity, glucose and lipids levels, and metabolomic profiling of polyphenols by LC-ESI-LTQ-Orbitrap-MS. The results demonstrated the in-vivo antioxidant properties in the animals liver, kidney and blood serum, as well as protective effects against hemolysis and rising of blood glucose and lipids levels. New insights on metabolomic profiling of polyphenols proved their absorption and further biotransformation by phase I (hydrogenation and hydroxylation) and II reactions (glucuronidation, methylation and sulfation). This is the first study that attempted to validate a novel nutraceutical ingredient extracted from CSS byin-vivoassays, corroborating the outcomes screened by in-vitro assays., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The purpose of the study was to determine the histopathological and In-vivo study of Moringa Oleifera Seed of moringa oleifera seed dietary. Fifty (50) albino rats were obtained from faculty of Health Science animal breeding centre, Obafemi Awolowo University, Ile-Ife, Nigeria. They were weighed and grouped into five groups of ten each and fed with five dietary samples for 28 days. Dietary samples investigated consisted of basal dietary, a nitrogen free diet 100% (1) control dietary (2) basal 80%: pressure cooked moringa seed 10%: soybean 10% (3) basal 80%: oven roasted moringa seed 10: soybean 10% (4) basal 80%: raw moringa seed 10%: Soybean 10% (5). The result revealed that histopathological study including spleen, heart, lungs, kidney, liver were healthy and chemical analysis such as pH, titratable acidity%, brix% and vitamin Cmg/100g were comparable with control samples, They were ranged from 6.05-6.60, 0.01-0.04%, 5-10% and 22.5-28.5 Cmg/100g. Proximate composition includes protein%, moisture%, fat%, ash%, crude fiber%, CHO% and caloric values. They were ranged from 10.20-10.30%, 4.25-4.34%, 2.68-3.80%, 2.30-2.64%, 0.68-0.88%, 79.07-88.85%, 382-389 Kcal% respectively. Histopathological and In-vivo study of formulated moringa samples dietary1-5 showed to improve health and promote growth. The tissues showed no infarcted zone, no oedema, no inflammatory cells and separation of cardiac muscle fibres, no cellular disintegration, and no toxicity symptom hence fit for human consumption. [ABSTRACT FROM AUTHOR]

[Display omitted] The aim of the current study was to prepare glutamic acid crosslinked poly(itaconic acid/methacrylic acid) microgels for pH-responsive delivery of ketorolac tromethamine, using aqueous free radical polymerization technique. The polymerization of polymer with monomers was carried out by a crosslinking agent N′, N′-methylene bisacrylamide in the presence of initiator ammonium persulfate. The prepared microgels were characterized for structure, surface morphology, thermal stability, and crystallinity. Similarly, studies such as sol-gel analysis, drug loading, and polymer volume fraction were performed for the fabricated microgels. The pH-sensitivity of the developed microgels was investigated at three different pH values i.e., pH 1.2, 4.6, and 7.4 by swelling and in-vitro drug release studies. Maximum swelling and drug release were found at pH 7.4 as compared to pH 1.2 and 4.6, which indicated the pH-sensitive nature of the prepared microgels. The toxicity of the prepared microgels was evaluated by cell line and HET-CAM test, which demonstrated no toxic effect of the prepared microgels. In-vivo study was carried out on rabbits and high plasma concentration was reported for the drug loaded microgels as compared to drug solution and commercial product Keten. Hence, the prepared microgel system could be employed as an excellent carrier for the controlled drug delivery system. [ABSTRACT FROM AUTHOR]

Inhibin α (INHα), a member of TGFβ superfamily, is an important modulator of reproductive function that plays a vital role in follicular changes, cell differentiation, oocyte development, and ultimately in mammalian reproduction. However, the role of inhibin α in female fertility and ovarian function remains largely unknown. To define its role in reproduction, transgenic mice of RNAi-INHα that knock down the INHα expression by shRNAi were used. Inhibin α subunit gene was knocked down successfully at both transcriptional and translational levels by RNAi PiggyBac transposon (Pbi) mediated recombinant pshRNA vectors and purified DNA fragments were microinjected into mouse zygotes. Results showed that transgenic female mice were sub-fertile and exhibited 35.28% reduction in litter size in F1 generation relative to wild type. The decreased litter size associated with the reduction in the number of oocytes ovulated after puberty. Serum INHα level was significantly decreased in both 3 and 6 weeks; whereas, FSH was significantly increased in 3 weeks but not in 6 weeks. Furthermore, suppression of INHα expression significantly promoted apoptosis by up-regulating Caspase-3, bcl2, INHβB and GDF9 and down regulated Kitl and TGFβRIII genes both at transcriptional and translational levels. Moreover, it also dramatically reduced the progression of G1 phase of cell cycle and the number of cells in S phase as determined by flow cytometer. These results indicate that suppression of INHα expression in RNAi-transgenic mice leads to disruption of normal ovarian regulatory mechanism and causes reproductive deficiencies by promoting cellular apoptosis, arresting cellular progression and altering hormonal signaling. [ABSTRACT FROM AUTHOR]

Glutamic acid-co-poly(acrylic acid) (GAcPAAc) hydrogels were prepared by the free radical polymerization technique using glutamic acid (GA) as a polymer, acrylic acid (AAc) as a monomer, ethylene glycol dimethylacrylate (EGDMA) as a cross-linker, and ammonium persulfate (APS) as an initiator. Increase in gel fraction was observed with the increasing concentration of glutamic acid, acrylic acid, and ethylene glycol dimethylacrylate. High percent porosity was indicated by developed hydrogels with the increase in the concentration of glutamic acid and acrylic acid, while a decrease was seen with the increasing concentration of EGDMA, respectively. Maximum swelling and drug release was exhibited at high pH 7.4 compared to low pH 1.2 by the newly synthesized hydrogels. Similarly, both swelling and drug release increased with the increasing concentration of glutamic acid and acrylic acid and decreased with the increase in ethylene glycol dimethylacrylate concentration. The drug release was considered as non-Fickian transport and partially controlled by viscoelastic relaxation of hydrogel. In-vivo study revealed that the AUC0–∞ of fabricated hydrogels significantly increased compared to the drug solution and commercial product Keten. Hence, the results indicated that the developed hydrogels could be used as a suitable carrier for controlled drug delivery. [ABSTRACT FROM AUTHOR]

Retinal diseases, such as age-related macular degeneration (AMD), are the leading cause of blindness in the elderly population. Since no known cures are currently present, it is crucial to diagnose the condition in its early stages so that disease progression is monitored. Recent advances show that the mechanical elasticity of the posterior eye changes with the onset of AMD. In this work, we present a quantitative method of mapping the mechanical elasticity of the posterior eye using confocal shear wave acoustic radiation force optical coherence elastography (SW-ARF-OCE). This technique has been developed and validated with both an ex-vivo porcine tissue model and a customized in-vivo rabbit model, which both showed the quantified elasticity variations between different layers. This study verifies the feasibility of using this technology for the quantification and diagnosis of retinal diseases from the in-vivo posterior eye.