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 with garlic (GL) and ginger (GR) oils, separately. Ursodeoxycholic acid and linoleic acid were individually incorporated as targeting moieties. RESULTS: Stability studies over 90 days showed average NES particle size, surface charge, polydispersity index, and entrapment efficiency 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. 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 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.

Association between HDL levels and stroke outcomes in the Arab population.

Low HDL levels are associated with an increased stroke incidence and worsened long-term outcomes. The aim of this study was to assess the relationship between HDL levels and long-term stroke outcomes in the Arab population. Patients admitted to the Qatar Stroke Database between 2014 and 2022 were included in the study and stratified into sex-specific HDL quartiles. Long-term outcomes included 90-Day modified Rankin Score (mRS), stroke recurrence, and post-stroke cardiovascular complications within 1 year of discharge. Multivariate binary logistic regression analyses were performed to identify the independent effect of HDL levels on short- and long-term outcomes. On multivariate binary logistic regression analyses, 1-year stroke recurrence was 2.24 times higher (p = 0.034) and MACE was 1.99 times higher (p = 0.009) in the low-HDL compared to the high-HDL group. Mortality at 1 year was 2.27-fold in the low-normal HDL group compared to the reference group (p = 0.049). Lower sex-specific HDL levels were independently associated with higher adjusted odds of 1-year post-stroke mortality, stroke recurrence, and MACE (p < 0.05). In patients who suffer a stroke, low HDL levels are associated with a higher risk of subsequent vascular complication.

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.

Parallelogram Excision: An Algorithmic Approach for Excision Designs in High-Tension Skin Areas.

INTRODUCTION: The excision of lesions that are not oriented along the skin tension lines may cause the surgeon to design extremely broad elliptical preoperative markings, with the intent to follow the tension lines as recommended for the best postoperative course and the best quality scars. The aim of this study is to describe and clinically apply a new surgical technique called the parallelogram excision technique, in which the traditional ellipse with a major axis parallel to the tension lines is converted into a parallelogram whose lesser sides are coincident with the local skin tension lines. This technique was specifically conceived for lesions whose major axis is non-coincident with skin tension lines, and the primary advantage is that it reduces the amount of healthy tissue excised. METHODS: Preliminarily to this clinical study, a comparative geometrical analysis was conducted between various excision shapes and angles using Geometry Pad version 2.7.10 (Bytes Arithmetic LLC) and verifying the data obtained through AutoCAD 2D 2016 (Autodesk, San Rafael, CA, USA), with the purpose of optimizing the technique from a geometrical point of view. A comparison was performed between the theoretical traditional elliptical excision and the hypothetical parallelogram excision. A pilot proof of concept clinical study was performed to verify the validity of the excisional design proposed. The patients considered for parallelogram excision suffered from skin lesions with a diameter no greater than 4 cm and oriented 45° to 60° with respect to tension lines. In order to limit variability, patients' ages were between 40 and 80, and the selected areas were limbs, sternum and dorsum. Scar quality was assessed with the validated POSAS method at 6 months post-operation. RESULTS: The geometrical analysis of the parallelogram's design showed that it allows a diminution of the excised healthy skin compared to the traditional ellipse. The clinical series included 16 patients, with a mean age of 63.5. Of these, nine patients were men and seven were women. Diagnoses included basal cell carcinoma in seven cases, dysplastic naevus in five patients, Bowen's disease in three individuals, and one case where a wider excision of a malignant melanoma was performed. Six-month follow up results showed: (1) an uneventful postoperative course; (2) good scar healing with an observer's POSAS median score of 16 and a patient's POSAS median score of 19; and (3) complete excision of lesions. CONCLUSIONS: When indicated, the parallelogram excision technique appears to be a good option for the excision and primary closure of skin lesions that are not parallel to skin tension lines, since it allows a reproducible and surgeon-friendly method of preoperative marking and implies a favorable use of the local tension, which determines good quality scars. The amount of healthy tissue removed is smaller compared to traditional elliptic excisions.

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.

Pharmacological and toxicological evaluation of methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxoide against haloperidol induced Parkinson like symptoms in animal model: In-vitro and in-vivo studies.

In Parkinson's disease (PD), degradation of dopaminergic neurons in substantia nigra causes striatal deficiency of dopamine, which results in tremors, bradykinesia with instability in posture, rigidity and shuffled gait. Prevalence of PD increases with age as from 65 to 85 years. In an attempt to devise targeted safe therapy, nanoparticles of methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (MBD) (MBDN), were prepared and their acute toxicity and safety was evaluated. Thirty-six healthy albino mice were randomly divided into six groups (n = 6): normal control, diseased control, standard (levodopa/carbidopa (100/25 mg/kg) and the remaining three groups were administered 1.25, 2.5 and 5 mg/kg MBDN during 21 days study. Except control, all mice, were injected haloperidol (1 mg/ kg i.p.) 1-h prior to treatment to induce PD. Acute toxicity test showed, no effect of MBDN on lipid profile, brain, renal and liver function and histoarchitecture of kidney, liver and heart, except decreased (p < 0.05) platelet count. Behavioral studies showed significant improvement (p < 0.001) in motor function and reduction of oxidation status in a MBDN in a dose dependent manner. Thus, the study findings revealed significance of MBDN as a selective MAO-B inhibitor for the improvement of Parkinson's symptoms in animal model.

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.

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.

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.

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.

Correction to Therapeutic Potential of Standardized Extract of Melilotus indicus (L.) All. and Its Phytochemicals against Skin Cancer in Animal Model: In Vitro, In Vivo, and In Silico Studies.

[This corrects the article DOI: 10.1021/acsomega.2c03053.].

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.

Designing Deferoxamine-Loaded Flaxseed Gum and Carrageenan-Based Controlled Release Biocomposite Hydrogel Films for Wound Healing.

In this study, biocomposite hydrogel films made from flaxseed gum (FSG)/kappa carrageenan (CGN) were fabricated, using potassium chloride as a crosslinker and glycerol as a plasticizer. The composite films were loaded with deferoxamine (DFX), an iron chelator that promotes neovascularization and angiogenesis for the healing of wounds. The properties of the biocomposite hydrogel films, including swelling, solubility, water vapor transmission rate, tensile strength, elongation at break, and Young's modulus studies, were tested. The films were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). In addition, drug release studies in PBS at pH 7.2 were investigated. In vivo analysis was performed by assessing the wound contraction in a full-thickness excisional wound rat model. Hematoxylin & eosin (H & E) and Masson's trichome staining were performed to evaluate the effect of the films on wound healing progress. The visual and micro-morphological analysis revealed the homogenous structure of the films; however, the elongation at break property decreased within the crosslinked film but increased for the drug-loaded film. The FTIR analysis confirmed the crosslinking due to potassium chloride. A superior resistance towards thermal degradation was confirmed by TGA for the crosslinked and drug-loaded films. Drug release from the optimum film was sustained for up to 24 h. In vivo testing demonstrated 100% wound contraction for the drug-loaded film group compared to 72% for the pure drug solution group. In light of the obtained results, the higher potential of the optimized biocomposite hydrogel film for wound healing applications was corroborated.