Bile acid/fatty acid integrated nanoemulsomes for nonalcoholic fatty liver targeted lovastatin delivery; stability, in-vitro, ex-vivo, and in-vivo analyses.

BACKGROUND: Controlled and targeted drug delivery to treat nonalcoholic fatty liver disease (NAFLD) can benefit from additive attributes of natural formulation ingredients incorporated into the drug delivery vehicles. METHODS: Lovastatin (LVN) loaded, bile acid (BA) and fatty acid (FA) integrated nanoemulsomes (NES) were formulated by thin layer hydration technique for synergistic and targeted delivery of LVN to treat NAFLD. Organic phase NES was comprised of stearic acid (StA) with garlic (GL) and ginger (GR) oils, separately. Ursodeoxycholic acid (UDA) and linoleic acid (LiA) were individually incorporated as targeting moieties. RESULTS: Stability studies over 90 days showed average NES particle size, surface charge, polydispersity index (PDI), and entrapment efficiency (EE) values of 270 ± 27.4 nm, -23.8 ± 3.5 mV, 0.2 ± 0.04 and 81.36 ± 3.4%, respectively. Spherical NES were observed under a transmission electron microscope (TEM). In-vitro LVN release depicted non-fickian release mechanisms from GL and GR oils-based NES. Ex-vivo permeation of BA/FA integrated NES through isolated rat intestines showed greater flux than non-integrated ones. CONCLUSION: Liver histopathology of experimental rats together with in-vivo lipid profiles and liver function tests (LFTs) illustrated that these NES possess the clinical potential to be promising drug carriers for NAFLD.

In Vitro and Biological Evaluation of Oral Fast-Disintegrating Films Containing Ranitidine HCl and Syloid® 244FP-Based Ternary Solid Dispersion of Flurbiprofen.

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H2 receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid® 244FP and poloxamer® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect.

Curcumin Encapsulation in Geranium Oil Microemulsion Elevates Its Antibacterial, Antioxidant, Anti-Inflammatory, and Anticancer Activities.

One of the major challenges with curcumin is its poor solubility in water, which limits its absorption and bioavailability in the body. This study aimed to develop and characterize stable microemulsions (MEs) as MEs increase the dispersibility of curcumin in water and aid its absorption in the body. Curcumin-loaded MEs were developed with the goal of enhancing topical delivery and its pharmacological activity (antioxidant, antibacterial, anticancer activity, and anti-inflammatory). The pseudoternary phase diagram was constructed to find out the desired microemulsion region. The prepared MEs (ME1-ME5) were evaluated for pH, viscosity, size of the particle, electrical conductivity, zeta potential, and ex vivo permeation of the drug. The optimized ME formulation was selected based on particle size and was further evaluated for biological activity (in vitro/vivo). In vitro cytotoxic effects of formulations were checked on the human liver cancer cell line, HEPG2 (a cell line exhibiting epithelial-like morphology that was isolated from a hepatocellular carcinoma). Geranium oil, Tween 80 (as a surfactant), and propylene glycol (as a cosurfactant) were screened out based on solubility to formulate MEs. The optimized ME formulation (ME5), with a composition of 20:50:30 (geranium oil:Tween 80:propylene glycol), exhibited pH 4.36 ± 0.057, conductivity of 40.06 ± 0.05 µS/cm, viscosity of 165 ± 0.37 mPa·s, and droplet diameter of 199.39 ± 0.017 nm. The ex vivo permeation study demonstrated a significant cumulative amount of curcumin permeated in 24 h and had a flux of 130.91 ± 0.02 µg/cm2/h. Antioxidant activity demonstrated that curcumin-loaded microemulsion (ME5) exhibited higher scavenging activity (99.27 ± 0.021%) than blank microemulsion (94.67 ± 0.001%). Optimized curcumin-loaded microemulsion (ME5) exhibited zones of inhibition of 25.18 and 28.37 mm against Escherichia coli and Staphylococcus aureus, respectively. Among the cell lines tested, a higher concentration of ME5 showed the greatest cytotoxicity with a % viability of 8.22 ± 1.09%. Evidently, it also revealed significant in vivo anti-inflammatory effects with 93.29 ± 0.030% inhibition by the carrageenan-induced paw edema model (6 h study) and 88.39 ± 0.002% inhibition by the formalin-induced paw edema model (14 day study). In conclusion, microemulsion was safe and effective for effective delivery of curcumin with the potential for antioxidant, antibacterial, cytotoxic, and in vivo anti-inflammatory activities.

Gut microbiome as a treatment in colorectal cancer.

BACKGROUND: The gut microbiome plays a role in the development and progression of colorectal cancer (CRC). AIM AND OBJECTIVE: This review focuses on whether the gut microbiome is involved in the development and regulation of the host immune system. METHODS: The gut microbiome can influence the production and activity of immune cells and molecules that help to maintain the integrity of the intestinal barrier and prevent inflammation. Gut microbiota modulates the anti-cancer immune response. The gut microbiota can influence the function of immune cells, like T cells, that recognize and eliminate cancer cells. Gut microbiota can affect various aspects of cancer progression and the efficacy of various anti-cancer treatments. RESULTS: Gut microbiota provide promise as a potential biomarker to identify the effect of immunotherapy and as a target for modulation to improve the efficacy of immunotherapy in CRC treatment. CONCLUSION: The potential synergistic effect between the gut microbiome and anti-cancer treatment modalities provides an interest in developing strategies to modulate the gut microbiome to improve the efficacy of anti-cancer treatment.

This review focuses on the gut microbiome in the development and regulation of the host immune system. Gut microbiota provides potential biomarkers to identify the effect of immunotherapy and as a target for modulation of immunotherapy in the treatment of CRC. This provides potential synergistic effects between the gut microbiome and anti-cancer treatment modalities.

Nanosizing of Lavender, Basil, and Clove Essential Oils into Microemulsions for Enhanced Antioxidant Potential and Antibacterial and Antibiofilm Activities.

Plant essential oils (EOs) possess significant bioactivities (antibacterial and antioxidant) and can be substituted for potentially harmful synthetic preservatives in the food industry. However, limited water solubility, bioavailability, volatility, and stability limit their use. Therefore, the goal of this research was nanosizing lavender essential oil (LEO), basil essential oil (BEO), and clove essential oil (CEO) in a microemulsion (ME) to improve their physicochemical attributes and bioefficacy. Tween 80 and Transcutol P were utilized for construction of pseudoternary phase diagrams. It was observed that the concentration of EOs had a great impact on the physicochemical and biological properties of MEs. A spherical droplet of MEs with a diameter of less than 20 nm with a narrower size distribution (polydispersity index (PDI) = 0.10-0.27) and a ζ potential of -0.27 to -9.03 was observed. ME formulations were also evaluated for viscosity, conductivity, and the refractive index. Moreover, the impact of delivery systems on the antibacterial property of EOs was assessed by determining the zone of inhibition and minimum inhibitory concentration against two distinct pathogen classes (S. aureus and E. coli). Crystal violet assay was used to measure the growth and development of biofilms. According to bioefficacy assays, ME demonstrated more efficient antibacterial activity against microorganisms at concentrations lower than pure EOs. CEO ME had superior activity againstS. aureus and E. coli. Similarly, dose-dependent antioxidant capacity was noted for MEs. Consequently, nanosized EO formulations with improved physicochemical properties and enhanced bioactivities can be employed in the food processing sector as a preservation agent.

Effect of hydrophilic polymers on the solubility and dissolution enhancement of rivaroxaban/beta-cyclodextrin inclusion complexes.

BCS class II drugs exhibit low aqueous solubility and high permeability. Such drugs often have an incomplete or erratic absorption profile. This study aimed to predict the effects of ß-cyclodextrin (ßCD) and different hydrophilic polymers (poloxamer 188 (PXM-188), polyvinyl pyrrolidone (PVP) and soluplus (SOLO)) on the saturated solubility and dissolution profile of hydrophobic model drug rivaroxaban (RIV). Binary inclusion complex with ßCD were prepared by kneading and solvent evaporation method, at drug to cyclodextrin weight molar ratios of 1:1, 1:2, and 1:4. Saturated solubility of the hydrophobic model moiety was evaluated with ßCD to explore the increment in saturated solubility. Dissolution test was carried out to assess the drug release from the produced binary inclusion complex in the aqueous medium. Solid state analysis was performed using Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) techniques. When compared to pure drug, the binary complex (Drug: ßCD at molar ratio of 1:2 w/w) demonstrated the best performance in terms of enhanced solubility and drug release. Furthermore, ternary inclusion complex was prepared with hydrophilic polymers SOLO, PVP K-30 and PXM-188 at 0.5%,1%,2.5%,5% and 10% w/w to optimized binary formulation RIV:ßCD (1:2) prepared by kneading (KN) and solvent evaporation (S.E) method. The findings demonstrated that among ternary formulations (1:2 Drug: ßCD: SOLO 10% S.E) manifested greatest improvement in saturated solubility and dissolution rate. Results of solubility enhancement and improvement in dissolution profile of model drug by ternary inclusion complexation were also supported by FTIR, DSC, XRD, and SEM analysis. So, it can be concluded that the ternary inclusion systems were more effective compared to the binary combinations in improving solubility as well as dissolution of hydrophobic model drug rivaroxaban.

In Vitro and In Vivo Evaluation of Composite Oral Fast Disintegrating Film: An Innovative Strategy for the Codelivery of Ranitidine HCl and Flurbiprofen.

Here, we evaluate the feasibility of co-loading plain ranitidine hydrochloride (RHCl) and microencapsulated flurbiprofen (FBP) in a Lycoat® RS780-based oral fast disintegrating film (ODF). These films were developed by the solvent casting method to minimize the adverse effects of FBP and reduce the dosage form burden on patients. Optimized FBP microparticles (M3) with an average size of 21.2 ± 9.2 µm were loaded alone (F1) and in combination with plain RHCl (F2) in the composite ODF. All films were evaluated physicomechanically and physicochemically. These films were resilient, flexible, and disintegrated within thirty seconds. SEM images showed intact FBP microparticles in both formulations and, moreover, did not observe an interaction between the drug and film components. Microencapsulated FBP was released in a controlled manner over 48 h from the proposed formulations, while RHCl was released within 5 min from F2. After in vitro evaluation, formulations were also tested for in vivo anti-inflammatory activity, cytokine (TNF-α and IL-6) levels, and gastroprotective effects in rats. The anti-inflammatory activity and gastroprotective effect of F2 were markedly higher than pure FBP and other synthesized formulations (M3 and F1). The average score of gastric lesions was in the order of pure FBP (15.5 ± 1.32) > M3 (8 ± 2) > F1 (1 ± 0.5) > F2 (0.5 ± 0) > control (0). Additionally, F2 showed a sustained anti-inflammatory effect up to 10 h in the rat paw edema model. Furthermore, F2 also markedly reduced TNF-α and IL-6 levels. Conclusively, the Lycoat® RS780-based composite film could be a promising carrier for the co-loading of microencapsulated FBP with RHCl. In the future, an optimized formulation (F2) could be capable of countering the issues related to multiple drug administration in geriatric patients and evading the gastric irritation associated with FBP.

Barriers and facilitators to integrating depression care in tuberculosis services in South Asia: a multi-country qualitative study.

BACKGROUND: Depression is common among people with tuberculosis (TB). The condition is typically unrecognised or untreated despite available and effective treatments in most low- and middle-income countries. TB services in these countries are relatively well established, offering a potential opportunity to deliver integrated depression screening and care. However, there is limited evidence on how such integration could be achieved. This study aimed to understand the barriers and facilitators to integrate depression care in TB services. METHODS: We conducted nine workshops with 76 study participants, including people with TB, their carers, and health service providers in Bangladesh, India, and Pakistan, seeking views on integrating depression care into TB clinics. We used a deductive thematic approach to analyse the translated transcripts of audio recordings, contemporaneous notes made during workshops for Bangladesh and India and workshop reports for Pakistan. Using the SURE (Supporting the Use of Research Evidence) thematic framework, we extracted and categorised barriers and facilitators into various domains. RESULTS: Reported barriers to integrating depression care in TB services included lack of knowledge about depression amongst patients and the staff, financial burden, and associated stigma for people with TB and their carers. Government buy-in and understanding of how to identify and screen for depression screening were potential facilitators reported. Additionally, breaking through mental health stigma and providing the additional resources required to deliver this service (human resources and consultation time) were essential for integrating depression and TB care. CONCLUSIONS: Depression is a common condition found among people with TB, requiring early identification among people with TB. Integrating depression care into Tb services by health workers requires the availability of political support and the provision of resources.

Green banking practices, bank reputation, and environmental awareness: evidence from Islamic banks in a developing economy.

Fulfilling the international considerations of environment, societal, and governance challenges, the financial industry, especially banks, has initiated "Go Green" practices to help sustain the environment and enhance "banking" across the globe. Amidst the green and climate-friendly drives, there is scarce literature highlighting the banks' green practices, environmental awareness, and their effects on bank reputation, especially the reputation of Islamic banks. This study aims to investigate the green banking practices of Islamic banks in a developing Islamic country. Focusing on the greening ambitions of banks, this study argues that the reputation of Islamic banks can be better enhanced through adopting green banking initiatives that will beget better climatic outcomes in Muslim societies. Therefore, the study illumes green banking practices and their impact on the reputation of Islamic banks in Pakistan. Moreover, this study checks the moderation effect of employees' environmental awareness on banks' reputation. The study used deductive rationale and quantified the employees' data to unravel their go-green perceptions and bank green activities. In this regard, the 390 response data, collected through a survey from the employees of Islamic banks, were analyzed through Smart-PLS, using structural equation modeling technique. The study finds that banks' employees-related practices (ERPs), daily operations-related practices (DORPs), customers-related practices (CRPs), and banks' policy-related practices (PRPs) have a significant positive influence on bank reputation. The authors also find that there is a significant moderating impact of environmental awareness between the relationships of ERPs, DORPs, CRPs, PRPs, and bank reputation. The study might increase understating and enlighten regulators and bank management to sustainably transform their operations to green banking practices, particularly adding to the environmental sustainability in Pakistan.

Identification of a Novel Nonsense Variant in the DLL3 Gene Underlying Spondylocostal Dysostosis in a Consanguineous Pakistani Family.

Introduction: Spondylocostal dysostosis (SCD) is characterized by multiple vertebral abnormalities associated with abnormalities of the ribs. Five genes causative for the disease have been identified. These include DLL3 (OMIM *602768), MESP2 (OMIM #608681), LFNG (OMIM #609813), TBX6 (OMIM *602427), and HES7 (OMIM *608059). Methods: In the current study, we investigated a Pakistani consanguineous family segregating spondylocostal dysotosis. Whole-exome sequencing (WES) followed by Sanger sequencing was performed using DNA of affected and unaffected individuals to identify pathogenic variant(s). The identified variant was interpreted using ACMG classification. Literature review was performed to summarize currently known mutated alleles of DLL3 and the underlying clinical phenotypes. Results: Clinical examination using anthropometric measurements and radiographs diagnosed the patients to be afflicted with SCD. Pedigree analysis of the affected family showed an autosomal recessive inheritance pattern of the disease. WES followed by Sanger sequencing identified a novel homozygous nonsense variant (DLL3(NM_016941.4): c.535G>T; p.Glu179Ter) in the DLL3 gene located on chromosome 19q13.2. Conclusion: The study will be helpful in carrier testing and genetic counseling to prevent segregation of the disease to the next generations within this family. It also provides knowledge for clinicians and researchers in search of a better understanding of SCD anomalies.

Development and evaluation of pH sensitive semi-interpenetrating networks: assessing the impact of itaconic acid and aloe vera on network swelling and cetirizine release.

Hydrogels are crosslinked three-dimensional networks, and their properties can be easily tuned to target the various segments of the gastrointestinal tract (GIT). Cetirizine HCl (CTZ HCl) is an antihistaminic drug, which when given orally can upset the stomach. Moreover, this molecule has shown maximum absorption in the intestine. To address these issues, we developed a pH-responsive semi-interpenetrating polymer network (semi-IPN) for the delivery of CTZ HCl to the lower part of the GIT. Initially, 10 different formulations of itaconic acid-grafted-poly (acrylamide)/aloe vera [IA-g-poly (AAm)/aloe vera] semi-IPN were developed by varying the concentration of IA and aloe vera using the free radical polymerization technique. Based on swelling and sol-gel analysis, formulation F5 containing 0.3%w/w aloe vera and 6%w/w IA was chosen as the optimum formulation. The solid-state characterization of the optimized formulation (F5) revealed a successful incorporation of CTZ HCl in semi-IPN without any drug-destabilizing interaction. The in vitro drug release from F5 showed limited release in acidic media followed by a controlled release in the intestinal environment for over 72 h. Furthermore, during the in vivo evaluation, formulation F5 did not affect the hematological parameters, kidney, and liver functions. Clinical observations did not reveal any signs of illness in rabbits treated with hydrogels. Histopathological images of vital organs of treated animals showed normal cellular architecture. Thus, the results suggest a non-toxic nature and overall potential of the developed formulation as a targeted drug carrier.

Anti-inflammatory mechanisms of eucalyptol rich Eucalyptus globulus essential oil alone and in combination with flurbiprofen.

Inflammation is the core contributor in the pathogenesis of various acute and chronic illness including appendicitis, bronchitis, arthritis, cancer and neurological diseases. NSAIDs, commonly used medications for inflammatory diseases, on prolonged use cause GI bleeding, ulcers and many more issues. Plant-based therapeutic agents including essential oils in combination with low-dose synthetic drugs have been shown to produce synergistic effects and reduce complications of synthetic drugs. This study was designed to evaluate the anti-inflammatory, analgesic and anti-pyretic properties of Eucalyptus globulus essential oil alone and in combination with flurbiprofen. GC-MS analysis was performed to screen chemical composition of oil. In vitro anti-inflammatory assay (membrane stabilization assay) and in vivo inflammatory acute (carrageenan and histamine-induced paw oedema) and chronic (cotton pellet-induced granuloma and Complete Freund's adjuvant-induced arthritis) models were performed to check anti-inflammatory properties. Acetic acid-induced algesia and yeast-induced pyrexia models were performed to check analgesic and anti-pyretic properties. qRT-PCR was performed to study the effect of treatments on the expression of inflammatory biomarkers. GC-MS analysis of E. globulus essential oil showed the presence of eucalyptol along with other active biomolecules. 500 + 10 mg/kg of oil-drug combination showed significantly (p < 0.05) better in vitro membrane stabilization effects as compared with groups treated with 500 mg/kg of E. globulus oil and 10 mg/kg of Flurbiprofen alone. 500 + 10 mg/kg of oil-drug combination showed significantly (p < 0.05) better anti-inflammatory, analgesic and antipyretic effects as compared to 500 mg/kg of E. globulus oil alone in all in vivo models. When comparison was done between 500 + 10 mg/kg of oil-drug combination-treated and 10 mg/kg Flurbiprofen-treated group, the former group showed significantly (p < 0.05) better anti-inflammatory and anti-pyretic effects, but there were non-significant differences in the analgesic model. Animal group treated with 10 mg/kg of Flurbiprofen showed significantly (p < 0.05) better anti-inflammatory and analgesic effects than group treated with 500 mg/kg of oil alone while, there were non-significant differences in anti-pyretic effects. qRT-PCR analysis showed significant (p < 0.05) down-regulation in the expression of IL-4 and TNF-α in serum samples of animals treated with 500 + 10 mg/kg of oil-drug combination as compared to the diseased control (arthritic) group. Overall, the current research demonstrates that Eucalyptus globulus essential oil in combination with flurbiprofen showed better anti-inflammatory, analgesic and anti-pyretic effects than oil and flurbiprofen alone which is attributed to the down-regulation of pro-inflammatory biomarkers (IL-4 and TNF-α). Further studies are required to formulate a stable dosage form and to check the anti-inflammatory efficacy in different inflammatory disorders.

Curcumin-Loaded Bioactive Polymer Composite Film of PVA/Gelatin/Tannic Acid Downregulates the Pro-inflammatory Cytokines to Expedite Healing of Full-Thickness Wounds.

Curcumin (Cur) entrapped poly(vinyl alcohol) (PVA)/gelatin composite films were prepared by cross-linking with tannic acid (TA) as bioactive dressings for rapid wound closure. Films were evaluated for mechanical strength, swelling index, water vapor transmission rate (WVTR), film solubility, and in-vitro drug release studies. SEM revealed uniform and smooth surfaces of blank (PG9) and Cur-loaded composite films (PGC4). PGC4 exhibited excellent mechanical strength (tensile strength (TS) and Young's modulus (YM) were 32.83 and 0.55 MPa, respectively), swelling ability (600-800% at pH 5.4, 7.4, and 9), WVTR (2003 ± 26), and film solubility (27.06 ± 2.0). Sustained release (81%) of the encapsulated payload was also observed for 72 h. The antioxidant activity determined by DPPH free radical scavenging showed that the PGC4 possessed strong % inhibition. The PGC4 formulation displayed higher antibacterial potential against S. aureus (14.55 mm zone of inhibition) and E. coli (13.00 mm zone of inhibition) compared to blank and positive control by the agar well diffusion method. An in-vivo wound healing study was carried out on rats using a full-thickness excisional wound model. Wounds treated with PGC4 showed very rapid healing about 93% in just 10 days post wounding as compared to 82.75% by Cur cream and 80.90% by PG9. Furthermore, histopathological studies showed ordered collagen deposition and angiogenesis along with fibroblast formation. PGC4 also exerted a strong anti-inflammatory effect by downregulating the expression of pro-inflammatory cytokines (TNF-α and IL-6 were lowered by 76% and 68% as compared to the untreated group, respectively). Therefore, Cur-loaded composite films can be an ideal delivery system for effective wound healing.

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

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

Design and evaluation of sodium alginate-based hydrogel dressings containing Betula utilis extract for cutaneous wound healing.

Traditional wound dressings have a limited capacity to absorb exudates, are permeable to microbes, and may adhere to wounds, which leads to secondary injuries. Hydrogels are promising alternative dressings to overcome the above challenges. In this study, we developed sodium alginate-based hydrogel films loaded with Betula utilis bark extract. These films were prepared via solvent-casting crosslinking method and evaluated for wound healing activity. Prepared films were 0.05-0.083 mm thick, flexible with folding endurance ranging from 197-203 folds, which indicates good physical properties. Optimized formulations exhibited successful loading of extract in the film matrix without any interaction as confirmed by FTIR. Maximum zone of inhibition against Gram-positive and Gram-negative bacteria was achieved by optimum formulation (B6), i.e., 19 mm and 9 mm, respectively, with > 90% scavenging activity. Furthermore, this optimum formulation (B6) was able to achieve 93% wound contraction in rats. Histograms of the optimized formulation treated group also revealed complete reepithelization of wounds. Conclusively, our extract-loaded hydrogel dressing successfully demonstrated its potential for cutaneous wound healing.

Axonal Regeneration: Underlying Molecular Mechanisms and Potential Therapeutic Targets.

Axons in the peripheral nervous system have the ability to repair themselves after damage, whereas axons in the central nervous system are unable to do so. A common and important characteristic of damage to the spinal cord, brain, and peripheral nerves is the disruption of axonal regrowth. Interestingly, intrinsic growth factors play a significant role in the axonal regeneration of injured nerves. Various factors such as proteomic profile, microtubule stability, ribosomal location, and signalling pathways mark a line between the central and peripheral axons' capacity for self-renewal. Unfortunately, glial scar development, myelin-associated inhibitor molecules, lack of neurotrophic factors, and inflammatory reactions are among the factors that restrict axonal regeneration. Molecular pathways such as cAMP, MAPK, JAK/STAT, ATF3/CREB, BMP/SMAD, AKT/mTORC1/p70S6K, PI3K/AKT, GSK-3ß/CLASP, BDNF/Trk, Ras/ERK, integrin/FAK, RhoA/ROCK/LIMK, and POSTN/integrin are activated after nerve injury and are considered significant players in axonal regeneration. In addition to the aforementioned pathways, growth factors, microRNAs, and astrocytes are also commendable participants in regeneration. In this review, we discuss the detailed mechanism of each pathway along with key players that can be potentially valuable targets to help achieve quick axonal healing. We also identify the prospective targets that could help close knowledge gaps in the molecular pathways underlying regeneration and shed light on the creation of more powerful strategies to encourage axonal regeneration after nervous system injury.

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

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

Circulating microbiota and metabolites: Insights into cardiovascular diseases.

BACKGROUND: In almost every country, cardiovascular diseases are the major cause of death, which are responsible for 17.7 million deaths worldwide, or 54% of all deaths. However, the latest evidence has shown that non-communicable diseases such as obesity, diabetes, and cardiovascular events are significantly influenced by the blood microbiota and circulating metabolites. METHODS: We searched online databases for the most recent related papers through the comprehensive international databases of the Institute of PubMed/ MEDLINE, ISI/WOS, and Scopus up to August 2022, using MESH terms and the related keywords in the English language. Considering the titles and abstracts, unrelated studies were excluded. The full texts of the remained studies were evaluated by authors, independently. Then, the studies' findings were assessed and reported. RESULTS: The study demonstrated that the bacterial profiles of patients with cardiovascular diseases and healthy individuals are significantly different. The diseased patients showed a significantly high abundance of phylum Proteobacteria, an important Proteobacterial component known as lipopolysaccharides that has been linked to the pathogenesis of cardiovascular disease, while phylum Firmicutes were found in healthy individuals. It suggests that Proteobacteria has a direct role in the onset of cardiovascular disease. CONCLUSION: We focused on the blood bacterial composition and circulating microbial metabolites in their relationship with the etiology and onset of cardiovascular disease. However, the various genera and species in the results reported were not always identical. Therefore, the microbial community structure of blood was more complicated and thus required a more in-depth exploration.

Physicochemical, rheological and antifungal evaluation of miconazole nitrate organogels for topical delivery.

Topical preparations have a problem of being wiped off after a short time, which results in low activity of the active moiety. In this research, topical organogels (OGs) were prepared with different oils for the controlled action of miconazole nitrate. Various oils were checked for their gel-forming ability. Controlled release OGs were prepared with a 15% concentration of glyceryl monostearate. Differential scanning calorimetry was performed to study the thermal behavior of gels. X-ray diffraction revealed that the drug was changed into an amorphous form from the crystalline form. The absence of any interaction between the active ingredient and excipients was concluded by Fourier Transform Infrared spectroscopy. Permeability studies were carried out with cellulose acetate membrane by using Franz diffusion cell containing phosphate buffer saline pH 7.4. The release of drug followed the Weibull model. A frequency sweep test was performed to study the rheological behavior of optimized formulations. Rheology revealed the true nature of formulations whether they are gels or just viscous fluids. Images of scanning electron microscopy showed a network formed by the gelator molecules. The antifungal activity was checked against C. albicans and A. niger and it was best by the formulation made by TT. It was concluded that all the OGs gave controlled topical antifungal action.

Assessment of Binary Agarose-Carbopol Buccal Gels for Mucoadhesive Drug Delivery: Ex Vivo and In Vivo Characterization.

Agarose (AG) is a naturally occurring biocompatible marine seaweed extract that is converted to hydrocolloid gel in hot water with notable gel strength. Currently, its mucoadhesion properties have not been fully explored. Therefore, the main aim of this study was to evaluate the mucoadhesive potential of AG binary dispersions in combination with Carbopol 934P (CP) as mucoadhesive gel preparations. The gels fabricated via homogenization were evaluated for ex vivo mucoadhesion, swelling index (SI), dissolution and stability studies. The mucoadhesive properties of AG were concentration dependent and it was improved by the addition of CP. Maximum mucoadhesive strength (MS) (27.03 g), mucoadhesive flow time (FT) (192.2 min), mucoadhesive time in volunteers (MT) (203.2 min) and SI (23.6% at 4 h) were observed with formulation F9. The mucoadhesive time investigated in volunteers (MT) was influenced by AG concentration and was greater than corresponding FT values. Formulations containing 0.3%, w/v AG (F3 and F9) were able to sustain the release (~99%) for both drugs till 3 h. The optimized formulation (F9) did not evoke any inflammation, irritation or pain in the buccal cavity of healthy volunteers and was also stable up to 6 months. Therefore, AG could be considered a natural and potential polymer with profound mucoadhesive properties to deliver drugs through the mucosal route.